                         SEQUENCE LISTING

<110>  Universitt Heidelberg
       Deutsches Krebsforschungszentrum
 
<120>  Use of anti-CRISPR polypeptides for specific activation of Cas 
       nucleases

<130>  UH14769PC

<150>  EP17186885.4
<151>  2017-08-18

<160>  50    

<170>  PatentIn version 3.3

<210>  1
<211>  72
<212>  DNA
<213>  Artificial

<220>
<223>  cloning scafold in Acr mRNA, partial sequence in Fig. 1B,

<400>  1
tgcagaatta gagacgccgt tgatgttgaa gtttatatac cgttgatgtt gaagtcgtct     60

ctagcttaag tt                                                         72


<210>  2
<211>  72
<212>  DNA
<213>  Artificial

<220>
<223>  Acr mRNA, partial sequence with miR122 target sequences, Fig. 1 B

<400>  2
tgcagaatta caaacaccat tgtcacactc cattatatac aaacaccatt gtcacactcc     60

atagcttaag tt                                                         72


<210>  3
<211>  7601
<212>  DNA
<213>  Artificial

<220>
<223>  Cas9 Luciferase Cleavage Reporter Plasmid

<400>  3
ctaaattgta agcgttaata ttttgttaaa attcgcgtta aatttttgtt aaatcagctc     60

attttttaac caataggccg aaatcggcaa aatcccttat aaatcaaaag aatagaccga    120

gatagggttg agtgttgttc cagtttggaa caagagtcca ctattaaaga acgtggactc    180

caacgtcaaa gggcgaaaaa ccgtctatca gggcgatggc ccactacgtg aaccatcacc    240

ctaatcaagt tttttggggt cgaggtgccg taaagcacta aatcggaacc ctaaagggag    300

cccccgattt agagcttgac ggggaaagcc ggcgaacgtg gcgagaaagg aagggaagaa    360

agcgaaagga gcgggcgcta gggcgctggc aagtgtagcg gtcacgctgc gcgtaaccac    420

cacacccgcc gcgcttaatg cgccgctaca gggcgcgtcc cattcgccat tcaggctgcg    480

caactgttgg gaagggcgat cggtgcgggc ctcttcgcta ttacgccagc tggccactcc    540

ctctctgcgc gctcgctcgc tcactgaggc cgggcgacca aaggtcgccc gacgcccggg    600

ctttgcccgg gcggcctcag tgagcgagcg agcgcgcaga gagggagtgg ccaactccat    660

cactaggggt tccttgtagt taatgattaa cccgccatgc tacttatcta cgtagccatg    720

ctctagagca agatctgcgc agcaccatgg cctgaaataa cctctgaaag aggaacttgg    780

ttaggtacct tctgaggcgg aaagaaccag ctgtggaatg tgtgtcagtt agggtgtgga    840

aagtccccag gctccccagc aggcagaagt atgcaaagca tgcatctcaa ttagtcagca    900

accaggtgtg gaaagtcccc aggctcccca gcaggcagaa gtatgcaaag catgcatctc    960

aattagtcag caaccatagt cccgccccta actccgccca tcccgcccct aactccgccc   1020

agttccgccc attctccgcc ccatggctga ctaatttttt ttatttatgc agaggccgag   1080

gccgcctcgg cctctgagct attccagaag tagtgaggag gcttttttgg aggcctaggc   1140

ttttgcaaaa agcttgattc ttctgacaca acagtctcga acttaagctg cagaagttgg   1200

tcgtgaggca ctgggcaggt aagtatcaag gttacaagac aggtttaagg agaccaatag   1260

aaactgggct tgtcgagaca gagaagactc ttgcgtttct gataggcacc tattggtctt   1320

actgacatcc actttgcctt tctctccaca ggtgtccact cccagttcaa ttacagctct   1380

taaggctaga gtacttaata cgactcacta taggctagcc accatggctt ccaaggtgta   1440

cgaccccgag caacgcaaac gcatgatcac tgggcctcag tggtgggctc gctgcaagca   1500

aatgaacgtg ctggactcct tcatcaacta ctatgattcc gagaagcacg ccgagaacgc   1560

cgtgattttt ctgcatggta acgctgcctc cagctacctg tggaggcacg tcgtgcctca   1620

catcgagccc gtggctagat gcatcatccc tgatctgatc ggaatgggta agtccggcaa   1680

gagcgggaat ggctcatatc gcctcctgga tcactacaag tacctcaccg cttggttcga   1740

gctgctgaac cttccaaaga aaatcatctt tgtgggccac gactgggggg cttgtctggc   1800

ctttcactac tcctacgagc accaagacaa gatcaaggcc atcgtccatg ctgagagtgt   1860

cgtggacgtg atcgagtcct gggacgagtg gcctgacatc gaggaggata tcgccctgat   1920

caagagcgaa gagggcgaga aaatggtgct tgagaataac ttcttcgtcg agaccatgct   1980

cccaagcaag atcatgcgga aactggagcc tgaggagttc gctgcctacc tggagccatt   2040

caaggagaag ggcgaggtta gacggcctac cctctcctgg cctcgcgaga tccctctcgt   2100

taagggaggc aagcccgacg tcgtccagat tgtccgcaac tacaacgcct accttcgggc   2160

cagcgacgat ctgcctaaga tgttcatcga gtccgaccct gggttctttt ccaacgctat   2220

tgtcgaggga gctaagaagt tccctaacac cgagttcgtg aaggtgaagg gcctccactt   2280

cagccaggag gacgctccag atgaaatggg taagtacatc aagagcttcg tggagcgcgt   2340

gctgaagaac gagcagtaat tctaggcgat cgctcgagcc cgggaattcg tttaaaccta   2400

gagcggccgc tggccgcaat aaaatatctt tattttcatt acatctgtgt gttggttttt   2460

tgtgtgagga tctaaatgag tcttcggacc tcgcgggggc cgcttaagcg gtggttaggg   2520

tttgtctgac gcggggggag ggggaaggaa cgaaacactc tcattcggag gcggctcggg   2580

gtttggtctt ggtggccacg ggcacgcaga agagcgccgc gatcctctta agcacccccc   2640

cgccctccgt ggaggcgggg gtttggtcgg cgggtggtaa ctggcgggcc gctgactcgg   2700

gcgggtcgcg cgccccagag tgtgaccttt tcggtctgct cgcagacccc cgggcggcgc   2760

cgccgcggcg gcgacgggct cgctgggtcc taggctccat ggggaccgta tacgtggaca   2820

ggctctggag catccgcacg actgcggtga tattaccgga gaccttctgc gggacgagcc   2880

gggtcacgcg gctgacgcgg agcgtccgtt gggcgacaaa caccaggacg gggcacaggt   2940

acactatctt gtcacccgga ggcgcgaggg actgcaggag cttcagggag tggcgcagct   3000

gcttcatccc cgtggcccgt tgctcgcgtt tgctggcggt gtccccggaa gaaatatatt   3060

tgcatgtctt tagttctatg atgacacaaa ccccgcccag cgtcttgtca ttggcgaatt   3120

cgaacacgca gatgcagtcg gggcggcgcg gtcccaggtc cacttcgcat attaaggtga   3180

cgcgtgtggc ctcgaacacc gagcgaccct gcagcgaccc gcttaaaagc ttggcattcc   3240

ggtactgttg gtaaagccac catggccgat gctaagaaca ttaagaaggg ccctgctccc   3300

ttctaccctc tggaggatgg caccgctggc gagcagctgc acaaggccat gaagaggtat   3360

gccctggtgc ctggcaccat tgccttcacc gatgcccaca ttgaggtgga catcacctat   3420

gccgagtact tcgagatgtc tgtgcgcctg gccgaggcca tgaagaggta cggcctgaac   3480

accaaccacc gcatcgtggt gtgctctgag aactctctgc agttcttcat gccagtgctg   3540

ggcgccctgt tcatcggagt ggccgtggcc cctgctaacg acatttacaa cgagcgcgag   3600

ctgctgaaca gcatgggcat ttctcagcct accgtggtgt tcgtgtctaa gaagggcctg   3660

cagaagatcc tgaacgtgca gaagaagctg cctatcatcc agaagatcat catcatggac   3720

tctaagaccg actaccaggg cttccagagc atgtacacat tcgtgacatc tcatctgcct   3780

cctggcttca acgagtacga cttcgtgcca gagtctttcg acagggacaa aaccattgcc   3840

ctgatcatga acagctctgg gtctaccggc ctgcctaagg gcgtggccct gcctcatcgc   3900

accgcctgtg tgcgcttctc tcacgcccgc gaccctattt tcggcaacca gatcatcccc   3960

gacaccgcta ttctgagcgt ggtgccattc caccacggct tcggcatgtt caccaccctg   4020

ggctacctga tttgcggctt tcgggtggtg ctgatgtacc gcttcgagga ggagctgttc   4080

ctgcgcagcc tgcaagacta caaaattcag tctgccctgc tggtgccaac cctgttcagc   4140

ttcttcgcta agagcaccct gatcgacaag tacgacctgt ctaacctgca cgagattgcc   4200

tctggcggcg ccccactgtc taaggaggtg ggcgaagccg tggccaagcg ctttcatctg   4260

ccaggcatcc gccagggcta cggcctgacc gagacaacca gcgccattct gattacccca   4320

gagggcgacg acaagcctgg cgccgtgggc aaggtggtgc cattcttcga ggccaaggtg   4380

gtggacctgg acaccggcaa gaccctggga gtgaaccagc gcggcgagct gtgtgtgcgc   4440

ggccctatga ttatgtccgg ctacgtgaat aaccctgagg ccacaaacgc cctgatcgac   4500

aaggacggct ggctgcactc tggcgacatt gcctactggg acgaggacga gcacttcttc   4560

atcgtggacc gcctgaagtc tctgatcaag tacaagggct accaggtggc cccagccgag   4620

ctggagtcta tcctgctgca gcaccctaac attttcgacg ccggagtggc cggcctgccc   4680

gacgacgatg ccggcgagct gcctgccgcc gtcgtcgtgc tggaacacgg caagaccatg   4740

accgagaagg agatcgtgga ctatgtggcc agccaggtga caaccgccaa gaagctgcgc   4800

ggcggagtgg tgttcgtgga cgaggtgccc aagggcctga ccggcaagct ggacgcccgc   4860

aagatccgcg agatcctgat caaggctaag aaaggcggca agatcgccgt gtaataattc   4920

tagagtcggg gcggccggcc gcttcgagca gacatgataa gatacattga tgagtttgga   4980

caaaccacaa ctagaatgca gtgaaaaaaa tgctttattt gtgaaatttg tgatgctatt   5040

gctttatttg taaccattat aagctgcaat aaacaagtta acaacaacaa ttgcattcat   5100

tttatgtttc aggttcaggg ggaggtgtgg gaggtttttt aaagcaagta aaacctctac   5160

aaatgtggta aaatcgatac tagtgcaaaa aaagcaccga ctcggtgcca ctttttcaag   5220

ttgataacgg actagcctta tttaaacttg ctatgctgtt tccagcatag ctcttaaacg   5280

gtagtcggtc ttagagtccg gtgtaccgtg gtctcataca gaacttataa gattcccaaa   5340

tccaaagaca tttcacgttt atggtgattt cccagaacac atagcgacat gcaaatatgg   5400

gcatcgataa actagttgct ctagagcatg gctacgtaga taagtagcat ggcgggttaa   5460

tcattaacta caaggaaccc ctagtgatgg agttggccac tccctctctg cgcgctcgct   5520

cgctcactga ggccgggcga ccaaaggtcg cccgacgccc gggctttgcc cgggcggcct   5580

cagtgagcga gcgagcgcgc agagagggag tggccagctg cattaatgaa tcggccaacg   5640

cgcggggaga ggcggtttgc gtattgggcg ctcttccgct tcctcgctca ctgactcgct   5700

gcgctcggtc gttcggctgc ggcgagcggt atcagctcac tcaaaggcgg taatacggtt   5760

atccacagaa tcaggggata acgcaggaaa gaacatgtga gcaaaaggcc agcaaaaggc   5820

caggaaccgt aaaaaggccg cgttgctggc gtttttccat aggctccgcc cccctgacga   5880

gcatcacaaa aatcgacgct caagtcagag gtggcgaaac ccgacaggac tataaagata   5940

ccaggcgttt ccccctggaa gctccctcgt gcgctctcct gttccgaccc tgccgcttac   6000

cggatacctg tccgcctttc tcccttcggg aagcgtggcg ctttctcata gctcacgctg   6060

taggtatctc agttcggtgt aggtcgttcg ctccaagctg ggctgtgtgc acgaaccccc   6120

cgttcagccc gaccgctgcg ccttatccgg taactatcgt cttgagtcca acccggtaag   6180

acacgactta tcgccactgg cagcagccac tggtaacagg attagcagag cgaggtatgt   6240

aggcggtgct acagagttct tgaagtggtg gcctaactac ggctacacta gaaggacagt   6300

atttggtatc tgcgctctgc tgaagccagt taccttcgga aaaagagttg gtagctcttg   6360

atccggcaaa caaaccaccg ctggtagcgg tggttttttt gtttgcaagc agcagattac   6420

gcgcagaaaa aaaggatctc aagaagatcc tttgatcttt tctacggggt ctgacgctca   6480

gtggaacgaa aactcacgtt aagggatttt ggtcatgaga ttatcaaaaa ggatcttcac   6540

ctagatcctt ttaaattaaa aatgaagttt taaatcaatc taaagtatat atgagtaaac   6600

ttggtctgac agttaccaat gcttaatcag tgaggcacct atctcagcga tctgtctatt   6660

tcgttcatcc atagttgcct gactccccgt cgtgtagata actacgatac gggagggctt   6720

accatctggc cccagtgctg caatgatacc gcgagaccca cgctcaccgg ctccagattt   6780

atcagcaata aaccagccag ccggaagggc cgagcgcaga agtggtcctg caactttatc   6840

cgcctccatc cagtctatta attgttgccg ggaagctaga gtaagtagtt cgccagttaa   6900

tagtttgcgc aacgttgttg ccattgctac aggcatcgtg gtgtcacgct cgtcgtttgg   6960

tatggcttca ttcagctccg gttcccaacg atcaaggcga gttacatgat cccccatgtt   7020

gtgcaaaaaa gcggttagct ccttcggtcc tccgatcgtt gtcagaagta agttggccgc   7080

agtgttatca ctcatggtta tggcagcact gcataattct cttactgtca tgccatccgt   7140

aagatgcttt tctgtgactg gtgagtactc aaccaagtca ttctgagaat agtgtatgcg   7200

gcgaccgagt tgctcttgcc cggcgtcaat acgggataat accgcgccac atagcagaac   7260

tttaaaagtg ctcatcattg gaaaacgttc ttcggggcga aaactctcaa ggatcttacc   7320

gctgttgaga tccagttcga tgtaacccac tcgtgcaccc aactgatctt cagcatcttt   7380

tactttcacc agcgtttctg ggtgagcaaa aacaggaagg caaaatgccg caaaaaaggg   7440

aataagggcg acacggaaat gttgaatact catactcttc ctttttcaat attattgaag   7500

catttatcag ggttattgtc tcatgagcgg atacatattt gaatgtattt agaaaaataa   7560

acaaataggg gttccgcgca catttccccg aaaagtgcca c                       7601


<210>  4
<211>  4848
<212>  DNA
<213>  Artificial

<220>
<223>  dCas9-VP64 transactivation luciferase reporter plasmid

<400>  4
gacgatatcc ctcgatcgag tttaccactc cctatcagtg atagagaaaa gtgaaagtcg     60

agtttaccac tccctatcag tgatagagaa aagtgaaagt cgagtttacc actccctatc    120

agtgatagag aaaagtgaaa gtcgagttta ccactcccta tcagtgatag agaaaagtga    180

aagtcgagtt taccactccc tatcagtgat agagaaaagt gaaagtcgag tttaccactc    240

cctatcagtg atagagaaaa gtgaaagtcg agtttaccac tccctatcag tgatagagaa    300

aagtgaaagt cgagtttacc actccctatc agtgatagag aaaagtgaaa gtcgagttta    360

ccactcccta tcagtgatag agaaaagtga aagtcgagtt taccactccc tatcagtgat    420

agagaaaagt gaaagtcgag tttaccactc cctatcagtg atagagaaaa gtgaaagtcg    480

agtttaccac tccctatcag tgatagagaa aagtgaaagt cgagtttacc actccctatc    540

agtgatagag aaaagtgaaa gtcgagctcg gtacgctatg gcatgcatgt gtcgcgacct    600

gcaggccctg aagttcatct gcaccaccgg caagctgccc gtgccctggc ccaccctcgt    660

gaccaccctg acctggggcg tgcagtgctt cgcccgctac cccgaccaca tgaagcagca    720

cgacttcttc aagtccgcca tgcccgaagg ctacgtccag gagcgcacca tcttcttcaa    780

ggacgacggc aactacaaga cccgcgccga ggtgaagttc gagggcgaca ccctggtgaa    840

ccgcatcgag ctgaagggca tcgacttcaa ggaggacggc aacatcctgg ggcacaagct    900

ggagtacaac gccatcagcg acaacgtcta tatcaccgcc gacaagcaga agaacggcat    960

caaggccaac ttcaagagct agccctatat aagcagagct cgtttagtga accgtcagat   1020

cgcctggaga cgccatccac gctgttttga cctccataga agacaccggg accgatccag   1080

cctccgcggc cccggtaccg aattcgccac catggaagat gccaaaaaca ttaagaaggg   1140

cccagcgcca ttctacccac tcgaagacgg gaccgccggc gagcagctgc acaaagccat   1200

gaagcgctac gccctggtgc ccggcaccat cgcctttacc gacgcacata tcgaggtgga   1260

cattacctac gccgagtact tcgagatgag cgttcggctg gcagaagcta tgaagcgcta   1320

tgggctgaat acaaaccatc ggatcgtggt gtgcagcgag aatagcttgc agttcttcat   1380

gcccgtgttg ggtgccctgt tcatcggtgt ggctgtggcc ccagctaacg acatctacaa   1440

cgagcgcgag ctgctgaaca gcatgggcat cagccagccc accgtcgtat tcgtgagcaa   1500

gaaagggctg caaaagatcc tcaacgtgca aaagaagcta ccgatcatac aaaagatcat   1560

catcatggat agcaagaccg actaccaggg cttccaaagc atgtacacct tcgtgacttc   1620

ccatttgcca cccggcttca acgagtacga cttcgtgccc gagagcttcg accgggacaa   1680

aaccatcgcc ctgatcatga acagtagtgg cagtaccgga ttgcccaagg gcgtagccct   1740

accgcaccgc accgcttgtg tccgattcag tcatgcccgc gaccccatct tcggcaacca   1800

gatcatcccc gacaccgcta tcctcagcgt ggtgccattt caccacggct tcggcatgtt   1860

caccacgctg ggctacttga tctgcggctt tcgggtcgtg ctcatgtacc gcttcgagga   1920

ggagctattc ttgcgcagct tgcaagacta taagattcaa tctgccctgc tggtgcccac   1980

actatttagc ttcttcgcta agagcactct catcgacaag tacgacctaa gcaacttgca   2040

cgagatcgcc agcggcgggg cgccgctcag caaggaggta ggtgaggccg tggccaaacg   2100

cttccaccta ccaggcatcc gccagggcta cggcctgaca gaaacaacca gcgccattct   2160

gatcaccccc gaaggggacg acaagcctgg cgcagtaggc aaggtggtgc ccttcttcga   2220

ggctaaggtg gtggacttgg acaccggtaa gacactgggt gtgaaccagc gcggcgagct   2280

gtgcgtccgt ggccccatga tcatgagcgg ctacgttaac aaccccgagg ctacaaacgc   2340

tctcatcgac aaggacggct ggctgcacag cggcgacatc gcctactggg acgaggacga   2400

gcacttcttc atcgtggacc ggctgaagag cctgatcaaa tacaagggct accaggtagc   2460

cccagccgaa ctggagagca tcctgctgca acaccccaac atcttcgacg ccggggtcgc   2520

cggcctgccc gacgacgatg ccggcgagct gcccgccgca gtcgtcgtgc tggaacacgg   2580

taaaaccatg accgagaagg agatcgtgga ctatgtggcc agccaggtta caaccgccaa   2640

gaagctgcgc ggtggtgttg tgttcgtgga cgaggtgcct aaaggactga ccggcaagtt   2700

ggacgcccgc aagatccgcg agattctcat taaggccaag aagtaaagat cttattaaag   2760

cagaacttgt ttattgcagc ttataatggt tacaaataaa gcaatagcat cacaaatttc   2820

acaaataaag catttttttc actgcattct agttgtggtt tgtccaaact catcaatgta   2880

tcttatcatg tctggtcgac tctagaatct tccgcttcct cgctcactga ctcgctgcgc   2940

tcggtcgttc ggctgcggcg agcggtatca gctcactcaa aggcggtaat acggttatcc   3000

acagaatcag gggataacgc aggaaagaac atgtgagcaa aaggccagca aaaggccagg   3060

aaccgtaaaa aggccgcgtt gctggcgttt ttccataggc tccgcccccc tgacgagcat   3120

cacaaaaatc gacgctcaag tcagaggtgg cgaaacccga caggactata aagataccag   3180

gcgtttcccc ctggaagctc cctcgtgcgc tctcctgttc cgaccctgcc gcttaccgga   3240

tacctgtccg cctttctccc ttcgggaagc gtggcgcttt ctcatagctc acgctgtagg   3300

tatctcagtt cggtgtaggt cgttcgctcc aagctgggct gtgtgcacga accccccgtt   3360

cagcccgacc gctgcgcctt atccggtaac tatcgtcttg agtccaaccc ggtaagacac   3420

gacttatcgc cactggcagc agccactggt aacaggatta gcagagcgag gtatgtaggc   3480

ggtgctacag agttcttgaa gtggtggcct aactacggct acactagaag gacagtattt   3540

ggtatctgcg ctctgctgaa gccagttacc ttcggaaaaa gagttggtag ctcttgatcc   3600

ggcaaacaaa ccaccgctgg tagcggtggt ttttttgttt gcaagcagca gattacgcgc   3660

agaaaaaaag gatctcaaga agatcctttg atcttttcta cggggtctga cgctcagtgg   3720

aacgaaaact cacgttaagg gattttggtc atgagattat caaaaaggat cttcacctag   3780

atccttttaa attaaaaatg aagttttaaa tcaatctaaa gtatatatga gtaaacttgg   3840

tctgacagtt accaatgctt aatcagtgag gcacctatct cagcgatctg tctatttcgt   3900

tcatccatag ttgcctgact ccccgtcgtg tagataacta cgatacggga gggcttacca   3960

tctggcccca gtgctgcaat gataccgcga gacccacgct caccggctcc agatttatca   4020

gcaataaacc agccagccgg aagggccgag cgcagaagtg gtcctgcaac tttatccgcc   4080

tccatccagt ctattaattg ttgccgggaa gctagagtaa gtagttcgcc agttaatagt   4140

ttgcgcaacg ttgttgccat tgctacaggc atcgtggtgt cacgctcgtc gtttggtatg   4200

gcttcattca gctccggttc ccaacgatca aggcgagtta catgatcccc catgttgtgc   4260

aaaaaagcgg ttagctcctt cggtcctccg atcgttgtca gaagtaagtt ggccgcagtg   4320

ttatcactca tggttatggc agcactgcat aattctctta ctgtcatgcc atccgtaaga   4380

tgcttttctg tgactggtga gtactcaacc aagtcattct gagaatagtg tatgcggcga   4440

ccgagttgct cttgcccggc gtcaatacgg gataataccg cgccacatag cagaacttta   4500

aaagtgctca tcattggaaa acgttcttcg gggcgaaaac tctcaaggat cttaccgctg   4560

ttgagatcca gttcgatgta acccactcgt gcacccaact gatcttcagc atcttttact   4620

ttcaccagcg tttctgggtg agcaaaaaca ggaaggcaaa atgccgcaaa aaagggaata   4680

agggcgacac ggaaatgttg aatactcata ctcttccttt ttcaatatta ttgaagcatt   4740

tatcagggtt attgtctcat gagcggatac atatttgaat gtatttagaa aaataaacaa   4800

ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtcgtc                4848


<210>  5
<211>  3226
<212>  DNA
<213>  Artificial

<220>
<223>   TetO-targeting gRNA fr dCas9-VP64 reporter plasmid

<400>  5
ctaaattgta agcgttaata ttttgttaaa attcgcgtta aatttttgtt aaatcagctc     60

attttttaac caataggccg aaatcggcaa aatcccttat aaatcaaaag aatagaccga    120

gatagggttg agtgttgttc cagtttggaa caagagtcca ctattaaaga acgtggactc    180

caacgtcaaa gggcgaaaaa ccgtctatca gggcgatggc ccactacgtg aaccatcacc    240

ctaatcaagt tttttggggt cgaggtgccg taaagcacta aatcggaacc ctaaagggag    300

cccccgattt agagcttgac ggggaaagcc ggcgaacgtg gcgagaaagg aagggaagaa    360

agcgaaagga gcgggcgcta gggcgctggc aagtgtagcg gtcacgctgc gcgtaaccac    420

cacacccgcc gcgcttaatg cgccgctaca gggcgcgtcc cattcgccat tcaggctgcg    480

caactgttgg gaagggcgat cggtgcgggc ctcttcgcta ttacgccagc tggcgaaagg    540

gggatgtgct gcaaggcgat taagttgggt aacgccaggg ttttcccagt cacgacgttg    600

taaaacgacg gccagtgagc gcgcgtaata cgactcacta tagggcgaat tgggtaccga    660

gggcctattt cccatgattc cttcatattt gcatatacga tacaaggctg ttagagagat    720

aattggaatt aatttgactg taaacacaaa gatattagta caaaatacgt gacgtagaaa    780

gtaataattt cttgggtagt ttgcagtttt aaaattatgt tttaaaatgg actatcatat    840

gcttatcgta acttgaaagt atttcgattt cttggcttta tatatcttgt ggaaaggacg    900

aaacaccgtc tctatcactg atagggaggt tttagagcta gaaatagcaa gttaaaataa    960

ggctagtccg ttatcaactt gaaaaagtgg caccgagtcg gtgctttttt tccgcggtgg   1020

agctccagct tttgttccct ttagtgaggg ttaattgcgc gcttggcgta atcatggtca   1080

tagctgtttc ctgtgtgaaa ttgttatccg ctcacaattc cacacaacat acgagccgga   1140

agcataaagt gtaaagcctg gggtgcctaa tgagtgagct aactcacatt aattgcgttg   1200

cgctcactgc ccgctttcca gtcgggaaac ctgtcgtgcc agctgcatta atgaatcggc   1260

caacgcgcgg ggagaggcgg tttgcgtatt gggcgctctt ccgcttcctc gctcactgac   1320

tcgctgcgct cggtcgttcg gctgcggcga gcggtatcag ctcactcaaa ggcggtaata   1380

cggttatcca cagaatcagg ggataacgca ggaaagaaca tgtgagcaaa aggccagcaa   1440

aaggccagga accgtaaaaa ggccgcgttg ctggcgtttt tccataggct ccgcccccct   1500

gacgagcatc acaaaaatcg acgctcaagt cagaggtggc gaaacccgac aggactataa   1560

agataccagg cgtttccccc tggaagctcc ctcgtgcgct ctcctgttcc gaccctgccg   1620

cttaccggat acctgtccgc ctttctccct tcgggaagcg tggcgctttc tcatagctca   1680

cgctgtaggt atctcagttc ggtgtaggtc gttcgctcca agctgggctg tgtgcacgaa   1740

ccccccgttc agcccgaccg ctgcgcctta tccggtaact atcgtcttga gtccaacccg   1800

gtaagacacg acttatcgcc actggcagca gccactggta acaggattag cagagcgagg   1860

tatgtaggcg gtgctacaga gttcttgaag tggtggccta actacggcta cactagaagg   1920

acagtatttg gtatctgcgc tctgctgaag ccagttacct tcggaaaaag agttggtagc   1980

tcttgatccg gcaaacaaac caccgctggt agcggtggtt tttttgtttg caagcagcag   2040

attacgcgca gaaaaaaagg atctcaagaa gatcctttga tcttttctac ggggtctgac   2100

gctcagtgga acgaaaactc acgttaaggg attttggtca tgagattatc aaaaaggatc   2160

ttcacctaga tccttttaaa ttaaaaatga agttttaaat caatctaaag tatatatgag   2220

taaacttggt ctgacagtta ccaatgctta atcagtgagg cacctatctc agcgatctgt   2280

ctatttcgtt catccatagt tgcctgactc cccgtcgtgt agataactac gatacgggag   2340

ggcttaccat ctggccccag tgctgcaatg ataccgcgag acccacgctc accggctcca   2400

gatttatcag caataaacca gccagccgga agggccgagc gcagaagtgg tcctgcaact   2460

ttatccgcct ccatccagtc tattaattgt tgccgggaag ctagagtaag tagttcgcca   2520

gttaatagtt tgcgcaacgt tgttgccatt gctacaggca tcgtggtgtc acgctcgtcg   2580

tttggtatgg cttcattcag ctccggttcc caacgatcaa ggcgagttac atgatccccc   2640

atgttgtgca aaaaagcggt tagctccttc ggtcctccga tcgttgtcag aagtaagttg   2700

gccgcagtgt tatcactcat ggttatggca gcactgcata attctcttac tgtcatgcca   2760

tccgtaagat gcttttctgt gactggtgag tactcaacca agtcattctg agaatagtgt   2820

atgcggcgac cgagttgctc ttgcccggcg tcaatacggg ataataccgc gccacatagc   2880

agaactttaa aagtgctcat cattggaaaa cgttcttcgg ggcgaaaact ctcaaggatc   2940

ttaccgctgt tgagatccag ttcgatgtaa cccactcgtg cacccaactg atcttcagca   3000

tcttttactt tcaccagcgt ttctgggtga gcaaaaacag gaaggcaaaa tgccgcaaaa   3060

aagggaataa gggcgacacg gaaatgttga atactcatac tcttcctttt tcaatattat   3120

tgaagcattt atcagggtta ttgtctcatg agcggataca tatttgaatg tatttagaaa   3180

aataaacaaa taggggttcc gcgcacattt ccccgaaaag tgccac                  3226


<210>  6
<211>  14547
<212>  DNA
<213>  Artificial

<220>
<223>   dCas9-VP64-2A-GFP

<400>  6
gtcgacggat cgggagatct cccgatcccc tatggtgcac tctcagtaca atctgctctg     60

atgccgcata gttaagccag tatctgctcc ctgcttgtgt gttggaggtc gctgagtagt    120

gcgcgagcaa aatttaagct acaacaaggc aaggcttgac cgacaattgc atgaagaatc    180

tgcttagggt taggcgtttt gcgctgcttc gcgatgtacg ggccagatat acgcgttgac    240

attgattatt gactagttat taatagtaat caattacggg gtcattagtt catagcccat    300

atatggagtt ccgcgttaca taacttacgg taaatggccc gcctggctga ccgcccaacg    360

acccccgccc attgacgtca ataatgacgt atgttcccat agtaacgcca atagggactt    420

tccattgacg tcaatgggtg gagtatttac ggtaaactgc ccacttggca gtacatcaag    480

tgtatcatat gccaagtacg ccccctattg acgtcaatga cggtaaatgg cccgcctggc    540

attatgccca gtacatgacc ttatgggact ttcctacttg gcagtacatc tacgtattag    600

tcatcgctat taccatggtg atgcggtttt ggcagtacat caatgggcgt ggatagcggt    660

ttgactcacg gggatttcca agtctccacc ccattgacgt caatgggagt ttgttttggc    720

accaaaatca acgggacttt ccaaaatgtc gtaacaactc cgccccattg acgcaaatgg    780

gcggtaggcg tgtacggtgg gaggtctata taagcagcgc gttttgcctg tactgggtct    840

ctctggttag accagatctg agcctgggag ctctctggct aactagggaa cccactgctt    900

aagcctcaat aaagcttgcc ttgagtgctt caagtagtgt gtgcccgtct gttgtgtgac    960

tctggtaact agagatccct cagacccttt tagtcagtgt ggaaaatctc tagcagtggc   1020

gcccgaacag ggacttgaaa gcgaaaggga aaccagagga gctctctcga cgcaggactc   1080

ggcttgctga agcgcgcacg gcaagaggcg aggggcggcg actggtgagt acgccaaaaa   1140

ttttgactag cggaggctag aaggagagag atgggtgcga gagcgtcagt attaagcggg   1200

ggagaattag atcgcgatgg gaaaaaattc ggttaaggcc agggggaaag aaaaaatata   1260

aattaaaaca tatagtatgg gcaagcaggg agctagaacg attcgcagtt aatcctggcc   1320

tgttagaaac atcagaaggc tgtagacaaa tactgggaca gctacaacca tcccttcaga   1380

caggatcaga agaacttaga tcattatata atacagtagc aaccctctat tgtgtgcatc   1440

aaaggataga gataaaagac accaaggaag ctttagacaa gatagaggaa gagcaaaaca   1500

aaagtaagac caccgcacag caagcggccg ctgatcttca gacctggagg aggagatatg   1560

agggacaatt ggagaagtga attatataaa tataaagtag taaaaattga accattagga   1620

gtagcaccca ccaaggcaaa gagaagagtg gtgcagagag aaaaaagagc agtgggaata   1680

ggagctttgt tccttgggtt cttgggagca gcaggaagca ctatgggcgc agcgtcaatg   1740

acgctgacgg tacaggccag acaattattg tctggtatag tgcagcagca gaacaatttg   1800

ctgagggcta ttgaggcgca acagcatctg ttgcaactca cagtctgggg catcaagcag   1860

ctccaggcaa gaatcctggc tgtggaaaga tacctaaagg atcaacagct cctggggatt   1920

tggggttgct ctggaaaact catttgcacc actgctgtgc cttggaatgc tagttggagt   1980

aataaatctc tggaacagat ttggaatcac acgacctgga tggagtggga cagagaaatt   2040

aacaattaca caagcttaat acactcctta attgaagaat cgcaaaacca gcaagaaaag   2100

aatgaacaag aattattgga attagataaa tgggcaagtt tgtggaattg gtttaacata   2160

acaaattggc tgtggtatat aaaattattc ataatgatag taggaggctt ggtaggttta   2220

agaatagttt ttgctgtact ttctatagtg aatagagtta ggcagggata ttcaccatta   2280

tcgtttcaga cccacctccc aaccccgagg ggacccgaca ggcccgaagg aatagaagaa   2340

gaaggtggag agagagacag agacagatcc attcgattag tgaacggatc ggcactgcgt   2400

gcgccaattc tgcagacaaa tggcagtatt catccacaat tttaaaagaa aaggggggat   2460

tggggggtac agtgcagggg aaagaatagt agacataata gcaacagaca tacaaactaa   2520

agaattacaa aaacaaatta caaaaattca aaattttcgg gtttattaca gggacagcag   2580

agatccagtt tggttaatta atgcaaagat ggataaagtt ttaaacagag aggaatcttt   2640

gcagctaatg gaccttctag gtcttgaaag gagtgggaat tggctccggt gcccgtcagt   2700

gggcagagcg cacatcgccc acagtccccg agaagttggg gggaggggtc ggcaattgaa   2760

ccggtgccta gagaaggtgg cgcggggtaa actgggaaag tgatgtcgtg tactggctcc   2820

gcctttttcc cgagggtggg ggagaaccgt atataagtgc agtagtcgcc gtgaacgttc   2880

tttttcgcaa cgggtttgcc gccagaacac aggtaagtgc cgtgtgtggt tcccgcgggc   2940

ctggcctctt tacgggttat ggcccttgcg tgccttgaat tacttccacc tggctgcagt   3000

acgtgattct tgatcccgag cttcgggttg gaagtgggtg ggagagttcg aggccttgcg   3060

cttaaggagc cccttcgcct cgtgcttgag ttgaggcctg gcctgggcgc tggggccgcc   3120

gcgtgcgaat ctggtggcac cttcgcgcct gtctcgctgc tttcgataag tctctagcca   3180

tttaaaattt ttgatgacct gctgcgacgc tttttttctg gcaagatagt cttgtaaatg   3240

cgggccaaga tctgcacact ggtatttcgg tttttggggc cgcgggcggc gacggggccc   3300

gtgcgtccca gcgcacatgt tcggcgaggc ggggcctgcg agcgcggcca ccgagaatcg   3360

gacgggggta gtctcaagct ggccggcctg ctctggtgcc tggcctcgcg ccgccgtgta   3420

tcgccccgcc ctgggcggca aggctggccc ggtcggcacc agttgcgtga gcggaaagat   3480

ggccgcttcc cggccctgct gcagggagct caaaatggag gacgcggcgc tcgggagagc   3540

gggcgggtga gtcacccaca caaaggaaaa gggcctttcc gtcctcagcc gtcgcttcat   3600

gtgactccac ggagtaccgg gcgccgtcca ggcacctcga ttagttctcg agcttttgga   3660

gtacgtcgtc tttaggttgg ggggaggggt tttatgcgat ggagtttccc cacactgagt   3720

gggtggagac tgaagttagg ccagcttggc acttgatgta attctccttg gaatttgccc   3780

tttttgagtt tggatcttgg ttcattctca agcctcagac agtggttcaa agtttttttc   3840

ttccatttca ggtgtcgtga cgtacggcca ccatgagccc caagaagaag agaaaggtgg   3900

aggccagcga caagaagtac agcatcggcc tggccatcgg caccaactct gtgggctggg   3960

ccgtgatcac cgacgagtac aaggtgccca gcaagaaatt caaggtgctg ggcaacaccg   4020

accggcacag catcaagaag aacctgatcg gagccctgct gttcgacagc ggcgaaacag   4080

ccgaggccac ccggctgaag agaaccgcca gaagaagata caccagacgg aagaaccgga   4140

tctgctatct gcaagagatc ttcagcaacg agatggccaa ggtggacgac agcttcttcc   4200

acagactgga agagtccttc ctggtggaag aggataagaa gcacgagcgg caccccatct   4260

tcggcaacat cgtggacgag gtggcctacc acgagaagta ccccaccatc taccacctga   4320

gaaagaaact ggtggacagc accgacaagg ccgacctgcg gctgatctat ctggccctgg   4380

cccacatgat caagttccgg ggccacttcc tgatcgaggg cgacctgaac cccgacaaca   4440

gcgacgtgga caagctgttc atccagctgg tgcagaccta caaccagctg ttcgaggaaa   4500

accccatcaa cgccagcggc gtggacgcca aggccatcct gtctgccaga ctgagcaaga   4560

gcagacggct ggaaaatctg atcgcccagc tgcccggcga gaagaagaat ggcctgttcg   4620

gcaacctgat tgccctgagc ctgggcctga cccccaactt caagagcaac ttcgacctgg   4680

ccgaggatgc caaactgcag ctgagcaagg acacctacga cgacgacctg gacaacctgc   4740

tggcccagat cggcgaccag tacgccgacc tgtttctggc cgccaagaac ctgtccgacg   4800

ccatcctgct gagcgacatc ctgagagtga acaccgagat caccaaggcc cccctgagcg   4860

cctctatgat caagagatac gacgagcacc accaggacct gaccctgctg aaagctctcg   4920

tgcggcagca gctgcctgag aagtacaaag agattttctt cgaccagagc aagaacggct   4980

acgccggcta cattgacggc ggagccagcc aggaagagtt ctacaagttc atcaagccca   5040

tcctggaaaa gatggacggc accgaggaac tgctcgtgaa gctgaacaga gaggacctgc   5100

tgcggaagca gcggaccttc gacaacggca gcatccccca ccagatccac ctgggagagc   5160

tgcacgccat tctgcggcgg caggaagatt tttacccatt cctgaaggac aaccgggaaa   5220

agatcgagaa gatcctgacc ttccgcatcc cctactacgt gggccctctg gccaggggaa   5280

acagcagatt cgcctggatg accagaaaga gcgaggaaac catcaccccc tggaacttcg   5340

aggaagtggt ggacaagggc gcttccgccc agagcttcat cgagcggatg accaacttcg   5400

ataagaacct gcccaacgag aaggtgctgc ccaagcacag cctgctgtac gagtacttca   5460

ccgtgtataa cgagctgacc aaagtgaaat acgtgaccga gggaatgaga aagcccgcct   5520

tcctgagcgg cgagcagaaa aaggccatcg tggacctgct gttcaagacc aaccggaaag   5580

tgaccgtgaa gcagctgaaa gaggactact tcaagaaaat cgagtgcttc gactccgtgg   5640

aaatctccgg cgtggaagat cggttcaacg cctccctggg cacataccac gatctgctga   5700

aaattatcaa ggacaaggac ttcctggaca atgaggaaaa cgaggacatt ctggaagata   5760

tcgtgctgac cctgacactg tttgaggaca gagagatgat cgaggaacgg ctgaaaacct   5820

atgcccacct gttcgacgac aaagtgatga agcagctgaa gcggcggaga tacaccggct   5880

ggggcaggct gagccggaag ctgatcaacg gcatccggga caagcagtcc ggcaagacaa   5940

tcctggattt cctgaagtcc gacggcttcg ccaacagaaa cttcatgcag ctgatccacg   6000

acgacagcct gacctttaaa gaggacatcc agaaagccca ggtgtccggc cagggcgata   6060

gcctgcacga gcacattgcc aatctggccg gcagccccgc cattaagaag ggcatcctgc   6120

agacagtgaa ggtggtggac gagctcgtga aagtgatggg ccggcacaag cccgagaaca   6180

tcgtgatcga aatggccaga gagaaccaga ccacccagaa gggacagaag aacagccgcg   6240

agagaatgaa gcggatcgaa gagggcatca aagagctggg cagccagatc ctgaaagaac   6300

accccgtgga aaacacccag ctgcagaacg agaagctgta cctgtactac ctgcagaatg   6360

ggcgggatat gtacgtggac caggaactgg acatcaaccg gctgtccgac tacgatgtgg   6420

acgctatcgt gcctcagagc tttctgaagg acgactccat cgacaacaag gtgctgacca   6480

gaagcgacaa gaaccggggc aagagcgaca acgtgccctc cgaagaggtc gtgaagaaga   6540

tgaagaacta ctggcggcag ctgctgaacg ccaagctgat tacccagaga aagttcgaca   6600

atctgaccaa ggccgagaga ggcggcctga gcgaactgga taaggccggc ttcatcaaga   6660

gacagctggt ggaaacccgg cagatcacaa agcacgtggc acagatcctg gactcccgga   6720

tgaacactaa gtacgacgag aatgacaagc tgatccggga agtgaaagtg atcaccctga   6780

agtccaagct ggtgtccgat ttccggaagg atttccagtt ttacaaagtg cgcgagatca   6840

acaactacca ccacgcccac gacgcctacc tgaacgccgt cgtgggaacc gccctgatca   6900

aaaagtaccc taagctggaa agcgagttcg tgtacggcga ctacaaggtg tacgacgtgc   6960

ggaagatgat cgccaagagc gagcaggaaa tcggcaaggc taccgccaag tacttcttct   7020

acagcaacat catgaacttt ttcaagaccg agattaccct ggccaacggc gagatccgga   7080

agcggcctct gatcgagaca aacggcgaaa ccggggagat cgtgtgggat aagggccggg   7140

attttgccac cgtgcggaaa gtgctgagca tgccccaagt gaatatcgtg aaaaagaccg   7200

aggtgcagac aggcggcttc agcaaagagt ctatcctgcc caagaggaac agcgataagc   7260

tgatcgccag aaagaaggac tgggacccta agaagtacgg cggcttcgac agccccaccg   7320

tggcctattc tgtgctggtg gtggccaaag tggaaaaggg caagtccaag aaactgaaga   7380

gtgtgaaaga gctgctgggg atcaccatca tggaaagaag cagcttcgag aagaatccca   7440

tcgactttct ggaagccaag ggctacaaag aagtgaaaaa ggacctgatc atcaagctgc   7500

ctaagtactc cctgttcgag ctggaaaacg gccggaagag aatgctggcc tctgccggcg   7560

aactgcagaa gggaaacgaa ctggccctgc cctccaaata tgtgaacttc ctgtacctgg   7620

ccagccacta tgagaagctg aagggctccc ccgaggataa tgagcagaaa cagctgtttg   7680

tggaacagca caagcactac ctggacgaga tcatcgagca gatcagcgag ttctccaaga   7740

gagtgatcct ggccgacgct aatctggaca aagtgctgtc cgcctacaac aagcaccggg   7800

ataagcccat cagagagcag gccgagaata tcatccacct gtttaccctg accaatctgg   7860

gagcccctgc cgccttcaag tactttgaca ccaccatcga ccggaagagg tacaccagca   7920

ccaaagaggt gctggacgcc accctgatcc accagagcat caccggcctg tacgagacac   7980

ggatcgacct gtctcagctg ggaggcgaca gcgctggagg aggtggaagc ggaggaggag   8040

gaagcggagg aggaggtagc ggacctaaga aaaagaggaa ggtggcggcc gctggatccg   8100

gacgggctga cgcattggac gattttgatc tggatatgct gggaagtgac gccctcgatg   8160

attttgacct tgacatgctt ggttcggatg cccttgatga ctttgacctc gacatgctcg   8220

gcagtgacgc ccttgatgat ttcgacctgg acatgctgat taacgctagc ggcagtggag   8280

agggcagagg aagtctgcta acatgcggtg acgtcgagga gaatcctggc ccagtgagca   8340

agggcgagga gctgttcacc ggggtggtgc ccatcctggt cgagctggac ggcgacgtaa   8400

acggccacaa gttcagcgtg tccggcgagg gcgagggcga tgccacctac ggcaagctga   8460

ccctgaagtt catctgcacc accggcaagc tgcccgtgcc ctggcccacc ctcgtgacca   8520

ccctgaccta cggcgtgcag tgcttcagcc gctaccccga ccacatgaag cagcacgact   8580

tcttcaagtc cgccatgccc gaaggctacg tccaggagcg caccatcttc ttcaaggacg   8640

acggcaacta caagacccgc gccgaggtga agttcgaggg cgacaccctg gtgaaccgca   8700

tcgagctgaa gggcatcgac ttcaaggagg acggcaacat cctggggcac aagctggagt   8760

acaactacaa cagccacaac gtctatatca tggccgacaa gcagaagaac ggcatcaagg   8820

tgaacttcaa gatccgccac aacatcgagg acggcagcgt gcagctcgcc gaccactacc   8880

agcagaacac ccccatcggc gacggccccg tgctgctgcc cgacaaccac tacctgagca   8940

cccagtccgc cctgagcaaa gaccccaacg agaagcgcga tcacatggtc ctgctggagt   9000

tcgtgaccgc cgccgggatc actctcggca tggacgagct gtacaagtaa gaattcgata   9060

tcaagcttat cgataatcaa cctctggatt acaaaatttg tgaaagattg actggtattc   9120

ttaactatgt tgctcctttt acgctatgtg gatacgctgc tttaatgcct ttgtatcatg   9180

ctattgcttc ccgtatggct ttcattttct cctccttgta taaatcctgg ttgctgtctc   9240

tttatgagga gttgtggccc gttgtcaggc aacgtggcgt ggtgtgcact gtgtttgctg   9300

acgcaacccc cactggttgg ggcattgcca ccacctgtca gctcctttcc gggactttcg   9360

ctttccccct ccctattgcc acggcggaac tcatcgccgc ctgccttgcc cgctgctgga   9420

caggggctcg gctgttgggc actgacaatt ccgtggtgtt gtcggggaaa tcatcgtcct   9480

ttccttggct gctcgcctgt gttgccacct ggattctgcg cgggacgtcc ttctgctacg   9540

tcccttcggc cctcaatcca gcggaccttc cttcccgcgg cctgctgccg gctctgcggc   9600

ctcttccgcg tcttcgcctt cgccctcaga cgagtcggat ctccctttgg gccgcctccc   9660

cgcatcgata ccgtcgacct cgagacctag aaaaacatgg agcaatcaca agtagcaata   9720

cagcagctac caatgctgat tgtgcctggc tagaagcaca agaggaggag gaggtgggtt   9780

ttccagtcac acctcaggta cctttaagac caatgactta caaggcagct gtagatctta   9840

gccacttttt aaaagaaaag gggggactgg aagggctaat tcactcccaa cgaagacaag   9900

atatccttga tctgtggatc taccacacac aaggctactt ccctgattgg cagaactaca   9960

caccagggcc agggatcaga tatccactga cctttggatg gtgctacaag ctagtaccag  10020

ttgagcaaga gaaggtagaa gaagccaatg aaggagagaa cacccgcttg ttacaccctg  10080

tgagcctgca tgggatggat gacccggaga gagaagtatt agagtggagg tttgacagcc  10140

gcctagcatt tcatcacatg gcccgagagc tgcatccgga ctgtactggg tctctctggt  10200

tagaccagat ctgagcctgg gagctctctg gctaactagg gaacccactg cttaagcctc  10260

aataaagctt gccttgagtg cttcaagtag tgtgtgcccg tctgttgtgt gactctggta  10320

actagagatc cctcagaccc ttttagtcag tgtggaaaat ctctagcagg gcccgtttaa  10380

acccgctgat cagcctcgac tgtgccttct agttgccagc catctgttgt ttgcccctcc  10440

cccgtgcctt ccttgaccct ggaaggtgcc actcccactg tcctttccta ataaaatgag  10500

gaaattgcat cgcattgtct gagtaggtgt cattctattc tggggggtgg ggtggggcag  10560

gacagcaagg gggaggattg ggaagacaat agcaggcatg ctggggatgc ggtgggctct  10620

atggcttctg aggcggaaag aaccagctgg ggctctaggg ggtatcccca cgcgccctgt  10680

agcggcgcat taagcgcggc gggggggggg ggggggtggg gcaggacagc aagggggagg  10740

attgggaaga caatagcagg catgctgggg atgcggtggg ctctatggct tctgaggcgg  10800

aaagaaccag ctggggctct agggggtatc cccacgcgcc ctgtagcggc gcattaagcg  10860

cggcgggtgt ggtggttacg cgcagcgtga ccgctacact tgccagcgcc ctagcgcccg  10920

ctcctttcgc tttcttccct tcctttctcg ccacgttcgc cggctttccc cgtcaagctc  10980

taaatcgggg gctcccttta gggttccgat ttagtgcttt acggcacctc gaccccaaaa  11040

aacttgatta gggtgatggt tcacgtagtg ggccatcgcc ctgatagacg gtttttcgcc  11100

ctttgacgtt ggagtccacg ttctttaata gtggactctt gttccaaact ggaacaacac  11160

tcaaccctat ctcggtctat tcttttgatt tataagggat tttgccgatt tcggcctatt  11220

ggttaaaaaa tgagctgatt taacaaaaat ttaacgcgaa ttaattctgt ggaatgtgtg  11280

tcagttaggg tgtggaaagt ccccaggctc cccagcaggc agaagtatgc aaagcatgca  11340

tctcaattag tcagcaacca ggtgtggaaa gtccccaggc tccccagcag gcagaagtat  11400

gcaaagcatg catctcaatt agtcagcaac catagtcccg cccctaactc cgcccatccc  11460

gcccctaact ccgcccagtt ccgcccattc tccgccccat ggctgactaa ttttttttat  11520

ttatgcagag gccgaggccg cctctgcctc tgagctattc cagaagtagt gaggaggctt  11580

ttttggaggc ctaggctttt gcaaaaagct cccgggagct tgtatatcca ttttcggatc  11640

tgatcagcac gtgttgacaa ttaatcatcg gcatagtata tcggcatagt ataatacgac  11700

aaggtgagga actaaaccat ggccaagttg accagtgccg ttccggtgct caccgcgcgc  11760

gacgtcgccg gagcggtcga gttctggacc gaccggctcg ggttctcccg ggacttcgtg  11820

gaggacgact tcgccggtgt ggtccgggac gacgtgaccc tgttcatcag cgcggtccag  11880

gaccaggtgg tgccggacaa caccctggcc tgggtgtggg tgcgcggcct ggacgagctg  11940

tacgccgagt ggtcggaggt cgtgtccacg aacttccggg acgcctccgg gccggccatg  12000

accgagatcg gcgagcagcc gtgggggcgg gagttcgccc tgcgcgaccc ggccggcaac  12060

tgcgtgcact tcgtggccga ggagcaggac tgacacgtgc tacgagattt cgattccacc  12120

gccgccttct atgaaaggtt gggcttcgga atcgttttcc gggacgccgg ctggatgatc  12180

ctccagcgcg gggatctcat gctggagttc ttcgcccacc ccaacttgtt tattgcagct  12240

tataatggtt acaaataaag caatagcatc acaaatttca caaataaagc atttttttca  12300

ctgcattcta gttgtggttt gtccaaactc atcaatgtat cttatcatgt ctgtataccg  12360

tcgacctcta gctagagctt ggcgtaatca tggtcatagc tgtttcctgt gtgaaattgt  12420

tatccgctca caattccaca caacatacga gccggaagca taaagtgtaa agcctggggt  12480

gcctaatgag tgagctaact cacattaatt gcgttgcgct cactgcccgc tttccagtcg  12540

ggaaacctgt cgtgccagct gcattaatga atcggccaac gcgcggggag aggcggtttg  12600

cgtattgggc gctcttccgc ttcctcgctc actgactcgc tgcgctcggt cgttcggctg  12660

cggcgagcgg tatcagctca ctcaaaggcg gtaatacggt tatccacaga atcaggggat  12720

aacgcaggaa agaacatgtg agcaaaaggc cagcaaaagg ccaggaaccg taaaaaggcc  12780

gcgttgctgg cgtttttcca taggctccgc ccccctgacg agcatcacaa aaatcgacgc  12840

tcaagtcaga ggtggcgaaa cccgacagga ctataaagat accaggcgtt tccccctgga  12900

agctccctcg tgcgctctcc tgttccgacc ctgccgctta ccggatacct gtccgccttt  12960

ctcccttcgg gaagcgtggc gctttctcat agctcacgct gtaggtatct cagttcggtg  13020

taggtcgttc gctccaagct gggctgtgtg cacgaacccc ccgttcagcc cgaccgctgc  13080

gccttatccg gtaactatcg tcttgagtcc aacccggtaa gacacgactt atcgccactg  13140

gcagcagcca ctggtaacag gattagcaga gcgaggtatg taggcggtgc tacagagttc  13200

ttgaagtggt ggcctaacta cggctacact agaagaacag tatttggtat ctgcgctctg  13260

ctgaagccag ttaccttcgg aaaaagagtt ggtagctctt gatccggcaa acaaaccacc  13320

gctggtagcg gtggtttttt tgtttgcaag cagcagatta cgcgcagaaa aaaaggatct  13380

caagaagatc ctttgatctt ttctacgggg tctgacgctc agtggaacga aaactcacgt  13440

taagggattt tggtcatgag attatcaaaa aggatcttca cctagatcct tttaaattaa  13500

aaatgaagtt ttaaatcaat ctaaagtata tatgagtaaa cttggtctga cagttaccaa  13560

tgcttaatca gtgaggcacc tatctcagcg atctgtctat ttcgttcatc catagttgcc  13620

tgactccccg tcgtgtagat aactacgata cgggagggct taccatctgg ccccagtgct  13680

gcaatgatac cgcgagaccc acgctcaccg gctccagatt tatcagcaat aaaccagcca  13740

gccggaaggg ccgagcgcag aagtggtcct gcaactttat ccgcctccat ccagtctatt  13800

aattgttgcc gggaagctag agtaagtagt tcgccagtta atagtttgcg caacgttgtt  13860

gccattgcta caggcatcgt ggtgtcacgc tcgtcgtttg gtatggcttc attcagctcc  13920

ggttcccaac gatcaaggcg agttacatga tcccccatgt tgtgcaaaaa agcggttagc  13980

tccttcggtc ctccgatcgt tgtcagaagt aagttggccg cagtgttatc actcatggtt  14040

atggcagcac tgcataattc tcttactgtc atgccatccg taagatgctt ttctgtgact  14100

ggtgagtact caaccaagtc attctgagaa tagtgtatgc ggcgaccgag ttgctcttgc  14160

ccggcgtcaa tacgggataa taccgcgcca catagcagaa ctttaaaagt gctcatcatt  14220

ggaaaacgtt cttcggggcg aaaactctca aggatcttac cgctgttgag atccagttcg  14280

atgtaaccca ctcgtgcacc caactgatct tcagcatctt ttactttcac cagcgtttct  14340

gggtgagcaa aaacaggaag gcaaaatgcc gcaaaaaagg gaataagggc gacacggaaa  14400

tgttgaatac tcatactctt cctttttcaa tattattgaa gcatttatca gggttattgt  14460

ctcatgagcg gatacatatt tgaatgtatt tagaaaaata aacaaatagg ggttccgcgc  14520

acatttcccc gaaaagtgcc acctgac                                      14547


<210>  7
<211>  5687
<212>  DNA
<213>  Artificial

<220>
<223>  CMV-AcrIIA4-2xmir122BS-BGH

<400>  7
agatctcccg atcccctatg gtgcactctc agtacaatct gctctgatgc cgcatagtta     60

agccagtatc tgctccctgc ttgtgtgttg gaggtcgctg agtagtgcgc gagcaaaatt    120

taagctacaa caaggcaagg cttgaccgac aattgcatga agaatctgct tagggttagg    180

cgttttgcgc tgcttcgcga tgtacgggcc agatatacgc gttgacattg attattgact    240

agttattaat agtaatcaat tacggggtca ttagttcata gcccatatat ggagttccgc    300

gttacataac ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc ccgcccattg    360

acgtcaataa tgacgtatgt tcccatagta acgccaatag ggactttcca ttgacgtcaa    420

tgggtggagt atttacggta aactgcccac ttggcagtac atcaagtgta tcatatgcca    480

agtacgcccc ctattgacgt caatgacggt aaatggcccg cctggcatta tgcccagtac    540

atgaccttat gggactttcc tacttggcag tacatctacg tattagtcat cgctattacc    600

atggtgatgc ggttttggca gtacatcaat gggcgtggat agcggtttga ctcacgggga    660

tttccaagtc tccaccccat tgacgtcaat gggagtttgt tttggcacca aaatcaacgg    720

gactttccaa aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg taggcgtgta    780

cggtgggagg tctatataag cagagctctc tggctaacta gagaacccac tgcttactgg    840

cttatcgaaa ttaatacgac tcactatagg gagacccaag ctggctagca tgaacattaa    900

cgacctgatt cgggaaataa agaacaagga ctacacggtc aagctgtcag gcaccgactc    960

caactctata acacagctca ttataagggt taataatgat ggcaacgaat atgtcatctc   1020

tgaatccgag aatgaatcaa tcgtggagaa attcatcagt gcatttaaaa acggctggaa   1080

ccaggagtac gaagatgagg aagagttcta caatgatatg caaactatca cactgaaatc   1140

tgagctgaac tagctcgagc ggccgccact gtgctggata tctgcagaat tacaaacacc   1200

attgtcacac tccattatat acaaacacca ttgtcacact ccatagctta agtttaaacc   1260

gctgatcagc ctcgactgtg ccttctagtt gccagccatc tgttgtttgc ccctcccccg   1320

tgccttcctt gaccctggaa ggtgccactc ccactgtcct ttcctaataa aatgaggaaa   1380

ttgcatcgca ttgtctgagt aggtgtcatt ctattctggg gggtggggtg gggcaggaca   1440

gcaaggggga ggattgggaa gacaatagca ggcatgctgg ggatgcggtg ggctctatgg   1500

cttctgaggc ggaaagaacc agctggggct ctagggggta tccccacgcg ccctgtagcg   1560

gcgcattaag cgcggcgggt gtggtggtta cgcgcagcgt gaccgctaca cttgccagcg   1620

ccctagcgcc cgctcctttc gctttcttcc cttcctttct cgccacgttc gccggctttc   1680

cccgtcaagc tctaaatcgg gggctccctt tagggttccg atttagtgct ttacggcacc   1740

tcgaccccaa aaaacttgat tagggtgatg gttcacgtag tgggccatcg ccctgataga   1800

cggtttttcg ccctttgacg ttggagtcca cgttctttaa tagtggactc ttgttccaaa   1860

ctggaacaac actcaaccct atctcggtct attcttttga tttataaggg attttgccga   1920

tttcggccta ttggttaaaa aatgagctga tttaacaaaa atttaacgcg aattaattct   1980

gtggaatgtg tgtcagttag ggtgtggaaa gtccccaggc tccccagcag gcagaagtat   2040

gcaaagcatg catctcaatt agtcagcaac caggtgtgga aagtccccag gctccccagc   2100

aggcagaagt atgcaaagca tgcatctcaa ttagtcagca accatagtcc cgcccctaac   2160

tccgcccatc ccgcccctaa ctccgcccag ttccgcccat tctccgcccc atggctgact   2220

aatttttttt atttatgcag aggccgaggc cgcctctgcc tctgagctat tccagaagta   2280

gtgaggaggc ttttttggag gcctaggctt ttgcaaaaag ctcccgggag cttgtatatc   2340

cattttcgga tctgatcaag agacaggatg aggatcgttt cgcatgattg aacaagatgg   2400

attgcacgca ggttctccgg ccgcttgggt ggagaggcta ttcggctatg actgggcaca   2460

acagacaatc ggctgctctg atgccgccgt gttccggctg tcagcgcagg ggcgcccggt   2520

tctttttgtc aagaccgacc tgtccggtgc cctgaatgaa ctgcaggacg aggcagcgcg   2580

gctatcgtgg ctggccacga cgggcgttcc ttgcgcagct gtgctcgacg ttgtcactga   2640

agcgggaagg gactggctgc tattgggcga agtgccgggg caggatctcc tgtcatctca   2700

ccttgctcct gccgagaaag tatccatcat ggctgatgca atgcggcggc tgcatacgct   2760

tgatccggct acctgcccat tcgaccacca agcgaaacat cgcatcgagc gagcacgtac   2820

tcggatggaa gccggtcttg tcgatcagga tgatctggac gaagagcatc aggggctcgc   2880

gccagccgaa ctgttcgcca ggctcaaggc gcgcatgccc gacggcgagg atctcgtcgt   2940

gacccatggc gatgcctgct tgccgaatat catggtggaa aatggccgct tttctggatt   3000

catcgactgt ggccggctgg gtgtggcgga ccgctatcag gacatagcgt tggctacccg   3060

tgatattgct gaagagcttg gcggcgaatg ggctgaccgc ttcctcgtgc tttacggtat   3120

cgccgctccc gattcgcagc gcatcgcctt ctatcgcctt cttgacgagt tcttctgagc   3180

gggactctgg ggttcgaaat gaccgaccaa gcgacgccca acctgccatc acgagatttc   3240

gattccaccg ccgccttcta tgaaaggttg ggcttcggaa tcgttttccg ggacgccggc   3300

tggatgatcc tccagcgcgg ggatctcatg ctggagttct tcgcccaccc caacttgttt   3360

attgcagctt ataatggtta caaataaagc aatagcatca caaatttcac aaataaagca   3420

tttttttcac tgcattctag ttgtggtttg tccaaactca tcaatgtatc ttatcatgtc   3480

tgtataccgt cgacctctag ctagagcttg gcgtaatcat ggtcatagct gtttcctgtg   3540

tgaaattgtt atccgctcac aattccacac aacatacgag ccggaagcat aaagtgtaaa   3600

gcctggggtg cctaatgagt gagctaactc acattaattg cgttgcgctc actgcccgct   3660

ttccagtcgg gaaacctgtc gtgccagctg cattaatgaa tcggccaacg cgcggggaga   3720

ggcggtttgc gtattgggcg ctcttccgct tcctcgctca ctgactcgct gcgctcggtc   3780

gttcggctgc ggcgagcggt atcagctcac tcaaaggcgg taatacggtt atccacagaa   3840

tcaggggata acgcaggaaa gaacatgtga gcaaaaggcc agcaaaaggc caggaaccgt   3900

aaaaaggccg cgttgctggc gtttttccat aggctccgcc cccctgacga gcatcacaaa   3960

aatcgacgct caagtcagag gtggcgaaac ccgacaggac tataaagata ccaggcgttt   4020

ccccctggaa gctccctcgt gcgctctcct gttccgaccc tgccgcttac cggatacctg   4080

tccgcctttc tcccttcggg aagcgtggcg ctttctcata gctcacgctg taggtatctc   4140

agttcggtgt aggtcgttcg ctccaagctg ggctgtgtgc acgaaccccc cgttcagccc   4200

gaccgctgcg ccttatccgg taactatcgt cttgagtcca acccggtaag acacgactta   4260

tcgccactgg cagcagccac tggtaacagg attagcagag cgaggtatgt aggcggtgct   4320

acagagttct tgaagtggtg gcctaactac ggctacacta gaagaacagt atttggtatc   4380

tgcgctctgc tgaagccagt taccttcgga aaaagagttg gtagctcttg atccggcaaa   4440

caaaccaccg ctggtagcgg tttttttgtt tgcaagcagc agattacgcg cagaaaaaaa   4500

ggatctcaag aagatccttt gatcttttct acggggtctg acgctcagtg gaacgaaaac   4560

tcacgttaag ggattttggt catgagatta tcaaaaagga tcttcaccta gatcctttta   4620

aattaaaaat gaagttttaa atcaatctaa agtatatatg agtaaacttg gtctgacagt   4680

taccaatgct taatcagtga ggcacctatc tcagcgatct gtctatttcg ttcatccata   4740

gttgcctgac tccccgtcgt gtagataact acgatacggg agggcttacc atctggcccc   4800

agtgctgcaa tgataccgcg agacccacgc tcaccggctc cagatttatc agcaataaac   4860

cagccagccg gaagggccga gcgcagaagt ggtcctgcaa ctttatccgc ctccatccag   4920

tctattaatt gttgccggga agctagagta agtagttcgc cagttaatag tttgcgcaac   4980

gttgttgcca ttgctacagg catcgtggtg tcacgctcgt cgtttggtat ggcttcattc   5040

agctccggtt cccaacgatc aaggcgagtt acatgatccc ccatgttgtg caaaaaagcg   5100

gttagctcct tcggtcctcc gatcgttgtc agaagtaagt tggccgcagt gttatcactc   5160

atggttatgg cagcactgca taattctctt actgtcatgc catccgtaag atgcttttct   5220

gtgactggtg agtactcaac caagtcattc tgagaatagt gtatgcggcg accgagttgc   5280

tcttgcccgg cgtcaatacg ggataatacc gcgccacata gcagaacttt aaaagtgctc   5340

atcattggaa aacgttcttc ggggcgaaaa ctctcaagga tcttaccgct gttgagatcc   5400

agttcgatgt aacccactcg tgcacccaac tgatcttcag catcttttac tttcaccagc   5460

gtttctgggt gagcaaaaac aggaaggcaa aatgccgcaa aaaagggaat aagggcgaca   5520

cggaaatgtt gaatactcat actcttcctt tttcaatatt attgaagcat ttatcagggt   5580

tattgtctca tgagcggata catatttgaa tgtatttaga aaaataaaca aataggggtt   5640

ccgcgcacat ttccccgaaa agtgccacct gacgtcgacg gatcggg                 5687


<210>  8
<211>  5687
<212>  DNA
<213>  Artificial

<220>
<223>  CMV-AcrIIA4-scaffold-BGH

<400>  8
agatctcccg atcccctatg gtgcactctc agtacaatct gctctgatgc cgcatagtta     60

agccagtatc tgctccctgc ttgtgtgttg gaggtcgctg agtagtgcgc gagcaaaatt    120

taagctacaa caaggcaagg cttgaccgac aattgcatga agaatctgct tagggttagg    180

cgttttgcgc tgcttcgcga tgtacgggcc agatatacgc gttgacattg attattgact    240

agttattaat agtaatcaat tacggggtca ttagttcata gcccatatat ggagttccgc    300

gttacataac ttacggtaaa tggcccgcct ggctgaccgc ccaacgaccc ccgcccattg    360

acgtcaataa tgacgtatgt tcccatagta acgccaatag ggactttcca ttgacgtcaa    420

tgggtggagt atttacggta aactgcccac ttggcagtac atcaagtgta tcatatgcca    480

agtacgcccc ctattgacgt caatgacggt aaatggcccg cctggcatta tgcccagtac    540

atgaccttat gggactttcc tacttggcag tacatctacg tattagtcat cgctattacc    600

atggtgatgc ggttttggca gtacatcaat gggcgtggat agcggtttga ctcacgggga    660

tttccaagtc tccaccccat tgacgtcaat gggagtttgt tttggcacca aaatcaacgg    720

gactttccaa aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg taggcgtgta    780

cggtgggagg tctatataag cagagctctc tggctaacta gagaacccac tgcttactgg    840

cttatcgaaa ttaatacgac tcactatagg gagacccaag ctggctagca tgaacattaa    900

cgacctgatt cgggaaataa agaacaagga ctacacggtc aagctgtcag gcaccgactc    960

caactctata acacagctca ttataagggt taataatgat ggcaacgaat atgtcatctc   1020

tgaatccgag aatgaatcaa tcgtggagaa attcatcagt gcatttaaaa acggctggaa   1080

ccaggagtac gaagatgagg aagagttcta caatgatatg caaactatca cactgaaatc   1140

tgagctgaac tagctcgagc ggccgccact gtgctggata tctgcagaat tagagacgcc   1200

gttgatgttg aagtttatat accgttgatg ttgaagtcgt ctctagctta agtttaaacc   1260

gctgatcagc ctcgactgtg ccttctagtt gccagccatc tgttgtttgc ccctcccccg   1320

tgccttcctt gaccctggaa ggtgccactc ccactgtcct ttcctaataa aatgaggaaa   1380

ttgcatcgca ttgtctgagt aggtgtcatt ctattctggg gggtggggtg gggcaggaca   1440

gcaaggggga ggattgggaa gacaatagca ggcatgctgg ggatgcggtg ggctctatgg   1500

cttctgaggc ggaaagaacc agctggggct ctagggggta tccccacgcg ccctgtagcg   1560

gcgcattaag cgcggcgggt gtggtggtta cgcgcagcgt gaccgctaca cttgccagcg   1620

ccctagcgcc cgctcctttc gctttcttcc cttcctttct cgccacgttc gccggctttc   1680

cccgtcaagc tctaaatcgg gggctccctt tagggttccg atttagtgct ttacggcacc   1740

tcgaccccaa aaaacttgat tagggtgatg gttcacgtag tgggccatcg ccctgataga   1800

cggtttttcg ccctttgacg ttggagtcca cgttctttaa tagtggactc ttgttccaaa   1860

ctggaacaac actcaaccct atctcggtct attcttttga tttataaggg attttgccga   1920

tttcggccta ttggttaaaa aatgagctga tttaacaaaa atttaacgcg aattaattct   1980

gtggaatgtg tgtcagttag ggtgtggaaa gtccccaggc tccccagcag gcagaagtat   2040

gcaaagcatg catctcaatt agtcagcaac caggtgtgga aagtccccag gctccccagc   2100

aggcagaagt atgcaaagca tgcatctcaa ttagtcagca accatagtcc cgcccctaac   2160

tccgcccatc ccgcccctaa ctccgcccag ttccgcccat tctccgcccc atggctgact   2220

aatttttttt atttatgcag aggccgaggc cgcctctgcc tctgagctat tccagaagta   2280

gtgaggaggc ttttttggag gcctaggctt ttgcaaaaag ctcccgggag cttgtatatc   2340

cattttcgga tctgatcaag agacaggatg aggatcgttt cgcatgattg aacaagatgg   2400

attgcacgca ggttctccgg ccgcttgggt ggagaggcta ttcggctatg actgggcaca   2460

acagacaatc ggctgctctg atgccgccgt gttccggctg tcagcgcagg ggcgcccggt   2520

tctttttgtc aagaccgacc tgtccggtgc cctgaatgaa ctgcaggacg aggcagcgcg   2580

gctatcgtgg ctggccacga cgggcgttcc ttgcgcagct gtgctcgacg ttgtcactga   2640

agcgggaagg gactggctgc tattgggcga agtgccgggg caggatctcc tgtcatctca   2700

ccttgctcct gccgagaaag tatccatcat ggctgatgca atgcggcggc tgcatacgct   2760

tgatccggct acctgcccat tcgaccacca agcgaaacat cgcatcgagc gagcacgtac   2820

tcggatggaa gccggtcttg tcgatcagga tgatctggac gaagagcatc aggggctcgc   2880

gccagccgaa ctgttcgcca ggctcaaggc gcgcatgccc gacggcgagg atctcgtcgt   2940

gacccatggc gatgcctgct tgccgaatat catggtggaa aatggccgct tttctggatt   3000

catcgactgt ggccggctgg gtgtggcgga ccgctatcag gacatagcgt tggctacccg   3060

tgatattgct gaagagcttg gcggcgaatg ggctgaccgc ttcctcgtgc tttacggtat   3120

cgccgctccc gattcgcagc gcatcgcctt ctatcgcctt cttgacgagt tcttctgagc   3180

gggactctgg ggttcgaaat gaccgaccaa gcgacgccca acctgccatc acgagatttc   3240

gattccaccg ccgccttcta tgaaaggttg ggcttcggaa tcgttttccg ggacgccggc   3300

tggatgatcc tccagcgcgg ggatctcatg ctggagttct tcgcccaccc caacttgttt   3360

attgcagctt ataatggtta caaataaagc aatagcatca caaatttcac aaataaagca   3420

tttttttcac tgcattctag ttgtggtttg tccaaactca tcaatgtatc ttatcatgtc   3480

tgtataccgt cgacctctag ctagagcttg gcgtaatcat ggtcatagct gtttcctgtg   3540

tgaaattgtt atccgctcac aattccacac aacatacgag ccggaagcat aaagtgtaaa   3600

gcctggggtg cctaatgagt gagctaactc acattaattg cgttgcgctc actgcccgct   3660

ttccagtcgg gaaacctgtc gtgccagctg cattaatgaa tcggccaacg cgcggggaga   3720

ggcggtttgc gtattgggcg ctcttccgct tcctcgctca ctgactcgct gcgctcggtc   3780

gttcggctgc ggcgagcggt atcagctcac tcaaaggcgg taatacggtt atccacagaa   3840

tcaggggata acgcaggaaa gaacatgtga gcaaaaggcc agcaaaaggc caggaaccgt   3900

aaaaaggccg cgttgctggc gtttttccat aggctccgcc cccctgacga gcatcacaaa   3960

aatcgacgct caagtcagag gtggcgaaac ccgacaggac tataaagata ccaggcgttt   4020

ccccctggaa gctccctcgt gcgctctcct gttccgaccc tgccgcttac cggatacctg   4080

tccgcctttc tcccttcggg aagcgtggcg ctttctcata gctcacgctg taggtatctc   4140

agttcggtgt aggtcgttcg ctccaagctg ggctgtgtgc acgaaccccc cgttcagccc   4200

gaccgctgcg ccttatccgg taactatcgt cttgagtcca acccggtaag acacgactta   4260

tcgccactgg cagcagccac tggtaacagg attagcagag cgaggtatgt aggcggtgct   4320

acagagttct tgaagtggtg gcctaactac ggctacacta gaagaacagt atttggtatc   4380

tgcgctctgc tgaagccagt taccttcgga aaaagagttg gtagctcttg atccggcaaa   4440

caaaccaccg ctggtagcgg tttttttgtt tgcaagcagc agattacgcg cagaaaaaaa   4500

ggatctcaag aagatccttt gatcttttct acggggtctg acgctcagtg gaacgaaaac   4560

tcacgttaag ggattttggt catgagatta tcaaaaagga tcttcaccta gatcctttta   4620

aattaaaaat gaagttttaa atcaatctaa agtatatatg agtaaacttg gtctgacagt   4680

taccaatgct taatcagtga ggcacctatc tcagcgatct gtctatttcg ttcatccata   4740

gttgcctgac tccccgtcgt gtagataact acgatacggg agggcttacc atctggcccc   4800

agtgctgcaa tgataccgcg agacccacgc tcaccggctc cagatttatc agcaataaac   4860

cagccagccg gaagggccga gcgcagaagt ggtcctgcaa ctttatccgc ctccatccag   4920

tctattaatt gttgccggga agctagagta agtagttcgc cagttaatag tttgcgcaac   4980

gttgttgcca ttgctacagg catcgtggtg tcacgctcgt cgtttggtat ggcttcattc   5040

agctccggtt cccaacgatc aaggcgagtt acatgatccc ccatgttgtg caaaaaagcg   5100

gttagctcct tcggtcctcc gatcgttgtc agaagtaagt tggccgcagt gttatcactc   5160

atggttatgg cagcactgca taattctctt actgtcatgc catccgtaag atgcttttct   5220

gtgactggtg agtactcaac caagtcattc tgagaatagt gtatgcggcg accgagttgc   5280

tcttgcccgg cgtcaatacg ggataatacc gcgccacata gcagaacttt aaaagtgctc   5340

atcattggaa aacgttcttc ggggcgaaaa ctctcaagga tcttaccgct gttgagatcc   5400

agttcgatgt aacccactcg tgcacccaac tgatcttcag catcttttac tttcaccagc   5460

gtttctgggt gagcaaaaac aggaaggcaa aatgccgcaa aaaagggaat aagggcgaca   5520

cggaaatgtt gaatactcat actcttcctt tttcaatatt attgaagcat ttatcagggt   5580

tattgtctca tgagcggata catatttgaa tgtatttaga aaaataaaca aataggggtt   5640

ccgcgcacat ttccccgaaa agtgccacct gacgtcgacg gatcggg                 5687


<210>  9
<211>  5302
<212>  DNA
<213>  Artificial

<220>
<223>   H1-scaffold_EF1alpha-AcrIIA4-scaffold-BGH (AAV construct)

<400>  9
tttctacggg gtctgacgct cagtggaacg aaaactcacg ttaagggatt ttggtcatga     60

gattatcaaa aaggatcttc acctagatcc ttttaaatta aaaatgaagt tttaaatcaa    120

tctaaagtat atatgagtaa acttggtctg acagttacca atgcttaatc agtgaggcac    180

ctatctcagc gatctgtcta tttcgttcat ccatagttgc ctgactcccc gtcgtgtaga    240

taactacgat acgggagggc ttaccatctg gccccagtgc tgcaatgata ccgcgagacc    300

cacgctcacc ggctccagat ttatcagcaa taaaccagcc agccggaagg gccgagcgca    360

gaagtggtcc tgcaacttta tccgcctcca tccagtctat taattgttgc cgggaagcta    420

gagtaagtag ttcgccagtt aatagtttgc gcaacgttgt tgccattgct acaggcatcg    480

tggtgtcacg ctcgtcgttt ggtatggctt cattcagctc cggttcccaa cgatcaaggc    540

gagttacatg atcccccatg ttgtgcaaaa aagcggttag ctccttcggt cctccgatcg    600

ttgtcagaag taagttggcc gcagtgttat cactcatggt tatggcagca ctgcataatt    660

ctcttactgt catgccatcc gtaagatgct tttctgtgac tggtgagtac tcaaccaagt    720

cattctgaga atagtgtatg cggcgaccga gttgctcttg cccggcgtca atacgggata    780

ataccgcgcc acatagcaga actttaaaag tgctcatcat tggaaaacgt tcttcggggc    840

gaaaactctc aaggatctta ccgctgttga gatccagttc gatgtaaccc actcgtgcac    900

ccaactgatc ttcagcatct tttactttca ccagcgtttc tgggtgagca aaaacaggaa    960

ggcaaaatgc cgcaaaaaag ggaataaggg cgacacggaa atgttgaata ctcatactct   1020

tcctttttca atattattga agcatttatc agggttattg tctcatgagc ggatacatat   1080

ttgaatgtat ttagaaaaat aaacaaatag gggttccgcg cacatttccc cgaaaagtgc   1140

cacctaaatt gtaagcgtta atattttgtt aaaattcgcg ttaaattttt gttaaatcag   1200

ctcatttttt aaccaatagg ccgaaatcgg caaaatccct tataaatcaa aagaatagac   1260

cgagataggg ttgagtgttg ttccagtttg gaacaagagt ccactattaa agaacgtgga   1320

ctccaacgtc aaagggcgaa aaaccgtcta tcagggcgat ggcccactac gtgaaccatc   1380

accctaatca agttttttgg ggtcgaggtg ccgtaaagca ctaaatcgga accctaaagg   1440

gagcccccga tttagagctt gacggggaaa gccggcgaac gtggcgagaa aggaagggaa   1500

gaaagcgaaa ggagcgggcg ctagggcgct ggcaagtgta gcggtcacgc tgcgcgtaac   1560

caccacaccc gccgcgctta atgcgccgct acagggcgcg tcccattcgc cattcaggct   1620

gcgcaactgt tgggaagggc gatcggtgcg ggcctcttcg ctattacgcc agctggcgaa   1680

agggggatgt gctgcaaggc gattaagttg ggtaacgcca gggttttccc agtcacgacg   1740

ttgtaaaacg acggccagtg agcgcgcgta atacgactca ctatagggcg aattggagct   1800

ctctagaatg cagggggggg gggggggggg ggccactccc tctctgcgcg ctcgctcgct   1860

cactgaggcc gggcgaccaa aggtcgcccg acgcccgggc tttgcccggg cggcctcagt   1920

gagcgagcga gcgcgcagag agggagtggc caactccatc actaggggtt cctagatctg   1980

atatcgtcga ccatagagcc caccgcatcc ccagcatgcc tgctattgtc ttcccaatcc   2040

tcccccttgc tgtcctgccc caccccaccc cccagaatag aatgacacct actcagacaa   2100

tgcgatgcaa tttcctcatt ttattaggaa aggacagtgg gagtggcacc ttccagggtc   2160

aaggaaggca cgggggaggg gcaaacaaca gatggctggc aactagaagg cacagtcgag   2220

gctgatcagc ggtttaaact taagctagag acgacttcaa catcaacggt atataaactt   2280

caacatcaac ggcgtctcta attctgcaga tatccagcac agtggcggcc gctcgagcta   2340

gttcagctca gatttcagtg tgatagtttg catatcattg tagaactctt cctcatcttc   2400

gtactcctgg ttccagccgt ttttaaatgc actgatgaat ttctccacga ttgattcatt   2460

ctcggattca gagatgacat attcgttgcc atcattatta acccttataa tgagctgtgt   2520

tatagagttg gagtcggtgc ctgacagctt gaccgtgtag tccttgttct ttatttcccg   2580

aatcaggtcg ttaatgttca tggtggcgga tccgctaatt cctcacgaca cctgaaatgg   2640

aagaaaaaaa ctttgaacca ctgtctgagg cttgagaatg aaccaagatc caaactcaaa   2700

aagggcaaat tccaaggaga attacatcaa gtgccaagct ggcctaactt cagtctccac   2760

ccactcagtg tggggaaact ccatcgcata aaacccctcc ccccaaccta aagacgacgt   2820

actccaaaag ctcgagaact aatcgaggtg cctggacggc gcccggtact ccgtggagtc   2880

acatgaagcg acggctgagg acggaaaggc ccttttcctt tgtgtgggtg actcacccgc   2940

ccgctctccc gagcgccgcg tcctccattt tgagctccct gcagcagggc cgggaagcgg   3000

ccatctttcc gctcacgcaa ctggtgccga ccgggccagc cttgccgccc agggcggggc   3060

gatacacggc ggcgcgaggc caggcaccag agcaggccgg ccagcttgag actacccccg   3120

tccgattctc ggtggccgcg ctcgcaggcc ccgcctcgcc gaacatgtgc gctgggacgc   3180

acgggccccg tcgccgcccg cggccccaaa aaccgaaata ccagtgtgca gatcttggcc   3240

cgcatttaca agactatctt gccagaaaaa aagcgtcgca gcaggtcatc aaaaatttta   3300

aatggctaga gacttatcga aagcagcgag acaggcgcga aggtgccacc agattcgcac   3360

gcggcggccc cagcgcccag gccaggcctc aactcaagca cgaggcgaag gggctcctta   3420

agcgcaaggc ctcgaactct cccacccact tccaacccga agctcgggat caagaatcac   3480

gtactgcagc caggtggaag taattcaagg cacgcaaggg ccataacccg taaagaggcc   3540

aggcccgcgg gaaccacaca cggcacttac ctgtgttctg gcggcaaacc cgttgcgaaa   3600

aagaacgttc acggcgacta ctgcacttat atacggttct cccccaccct cgggaaaaag   3660

gcggagccag tacacgacat cactttccca gtttaccccg cgccaccttc tctaggcacc   3720

ggttcaattg ccgacccctc cccccaactt ctcggggact gtgggcgatg tgcgctctgc   3780

ccactgacgg gcaccggagc ctcacgggcc gcaaaaaaag caccgactcg gtgccacttt   3840

ttcaagttga taacggacta gccttattta aacttgctat gctgtttcca gcatagctct   3900

taaacctgtc ttcctcgaag actcggtgta ccgtggtctc atacagaact tataagattc   3960

ccaaatccaa agacatttca cgtttatggt gatttcccag aacacatagc gacatgcaaa   4020

tatgggcgcg ccgatatcag atctggcaaa cctagatgat ggaggtaccc actccctcta   4080

tgcgcgctcg ctcactcact cggccctgcc ggccagaggc cggcagtctg gagacctttg   4140

gtctccaggg ccgagtgagt gagcgagcgc gcatagaggg agtgggtagg acgcgtcctg   4200

caggatgcat actagtggta cccagctttt gttcccttta gtgagggtta attgcgcgct   4260

tggcgtaatc atggtcatag ctgtttcctg tgtgaaattg ttatccgctc acaattccac   4320

acaacatacg agccggaagc ataaagtgta aagcctgggg tgcctaatga gtgagctaac   4380

tcacattaat tgcgttgcgc tcactgcccg ctttccagtc gggaaacctg tcgtgccagc   4440

tgcattaatg aatcggccaa cgcgcgggga gaggcggttt gcgtattggg cgctcttccg   4500

cttcctcgct cactgactcg ctgcgctcgg tcgttcggct gcggcgagcg gtatcagctc   4560

actcaaaggc ggtaatacgg ttatccacag aatcagggga taacgcagga aagaacatgt   4620

gagcaaaagg ccagcaaaag gccaggaacc gtaaaaaggc cgcgttgctg gcgtttttcc   4680

ataggctccg cccccctgac gagcatcaca aaaatcgacg ctcaagtcag aggtggcgaa   4740

acccgacagg actatacata tttgcatgtc gctatgtgaa gataccaggc gtttccccct   4800

ggaagctccc tcgtgcgctc tcctgttccg accctgccgc ttaccggata cctgtccgcc   4860

tttctccctt cgggaagcgt ggcgctttct catagctcac gctgtaggta tctcagttcg   4920

gtgtaggtcg ttcgctccaa gctgggctgt gtgcacgaac cccccgttca gcccgaccgc   4980

tgcgccttat ccggtaacta tcgtcttgag tccaacccgg taagacacga cttatcgcca   5040

ctggcagcag ccactggtaa caggattagc agagcgaggt atgtaggcgg tgctacagag   5100

ttcttgaagt ggtggcctaa ctacggctac actagaagga cagtatttgg tatctgcgct   5160

ctgctgaagc cagttacctt cggaaaaaga gttggtagct cttgatccgg caaacaaacc   5220

accgctggta gcggtggttt ttttgtttgc aagcagcaga ttacgcgcag aaaaaaagga   5280

tctcaagaag atcctttgat ct                                            5302


<210>  10
<211>  5302
<212>  DNA
<213>  Artificial

<220>
<223>  H1-scaffold_EF1alpha-AcrIIA4-2xmir122BS-BGH (AAV construct)

<400>  10
agatcaaagg atcttcttga gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa     60

aaaaaccacc gctaccagcg gtggtttgtt tgccggatca agagctacca actctttttc    120

cgaaggtaac tggcttcagc agagcgcaga taccaaatac tgtccttcta gtgtagccgt    180

agttaggcca ccacttcaag aactctgtag caccgcctac atacctcgct ctgctaatcc    240

tgttaccagt ggctgctgcc agtggcgata agtcgtgtct taccgggttg gactcaagac    300

gatagttacc ggataaggcg cagcggtcgg gctgaacggg gggttcgtgc acacagccca    360

gcttggagcg aacgacctac accgaactga gatacctaca gcgtgagcta tgagaaagcg    420

ccacgcttcc cgaagggaga aaggcggaca ggtatccggt aagcggcagg gtcggaacag    480

gagagcgcac gagggagctt ccagggggaa acgcctggta tcttcacata gcgacatgca    540

aatatgtata gtcctgtcgg gtttcgccac ctctgacttg agcgtcgatt tttgtgatgc    600

tcgtcagggg ggcggagcct atggaaaaac gccagcaacg cggccttttt acggttcctg    660

gccttttgct ggccttttgc tcacatgttc tttcctgcgt tatcccctga ttctgtggat    720

aaccgtatta ccgcctttga gtgagctgat accgctcgcc gcagccgaac gaccgagcgc    780

agcgagtcag tgagcgagga agcggaagag cgcccaatac gcaaaccgcc tctccccgcg    840

cgttggccga ttcattaatg cagctggcac gacaggtttc ccgactggaa agcgggcagt    900

gagcgcaacg caattaatgt gagttagctc actcattagg caccccaggc tttacacttt    960

atgcttccgg ctcgtatgtt gtgtggaatt gtgagcggat aacaatttca cacaggaaac   1020

agctatgacc atgattacgc caagcgcgca attaaccctc actaaaggga acaaaagctg   1080

ggtaccacta gtatgcatcc tgcaggacgc gtcctaccca ctccctctat gcgcgctcgc   1140

tcactcactc ggccctggag accaaaggtc tccagactgc cggcctctgg ccggcagggc   1200

cgagtgagtg agcgagcgcg catagaggga gtgggtacct ccatcatcta ggtttgccag   1260

atctgatatc ggcgcgccca tatttgcatg tcgctatgtg ttctgggaaa tcaccataaa   1320

cgtgaaatgt ctttggattt gggaatctta taagttctgt atgagaccac ggtacaccga   1380

gtcttcgagg aagacaggtt taagagctat gctggaaaca gcatagcaag tttaaataag   1440

gctagtccgt tatcaacttg aaaaagtggc accgagtcgg tgcttttttt gcggcccgtg   1500

aggctccggt gcccgtcagt gggcagagcg cacatcgccc acagtccccg agaagttggg   1560

gggaggggtc ggcaattgaa ccggtgccta gagaaggtgg cgcggggtaa actgggaaag   1620

tgatgtcgtg tactggctcc gcctttttcc cgagggtggg ggagaaccgt atataagtgc   1680

agtagtcgcc gtgaacgttc tttttcgcaa cgggtttgcc gccagaacac aggtaagtgc   1740

cgtgtgtggt tcccgcgggc ctggcctctt tacgggttat ggcccttgcg tgccttgaat   1800

tacttccacc tggctgcagt acgtgattct tgatcccgag cttcgggttg gaagtgggtg   1860

ggagagttcg aggccttgcg cttaaggagc cccttcgcct cgtgcttgag ttgaggcctg   1920

gcctgggcgc tggggccgcc gcgtgcgaat ctggtggcac cttcgcgcct gtctcgctgc   1980

tttcgataag tctctagcca tttaaaattt ttgatgacct gctgcgacgc tttttttctg   2040

gcaagatagt cttgtaaatg cgggccaaga tctgcacact ggtatttcgg tttttggggc   2100

cgcgggcggc gacggggccc gtgcgtccca gcgcacatgt tcggcgaggc ggggcctgcg   2160

agcgcggcca ccgagaatcg gacgggggta gtctcaagct ggccggcctg ctctggtgcc   2220

tggcctcgcg ccgccgtgta tcgccccgcc ctgggcggca aggctggccc ggtcggcacc   2280

agttgcgtga gcggaaagat ggccgcttcc cggccctgct gcagggagct caaaatggag   2340

gacgcggcgc tcgggagagc gggcgggtga gtcacccaca caaaggaaaa gggcctttcc   2400

gtcctcagcc gtcgcttcat gtgactccac ggagtaccgg gcgccgtcca ggcacctcga   2460

ttagttctcg agcttttgga gtacgtcgtc tttaggttgg ggggaggggt tttatgcgat   2520

ggagtttccc cacactgagt gggtggagac tgaagttagg ccagcttggc acttgatgta   2580

attctccttg gaatttgccc tttttgagtt tggatcttgg ttcattctca agcctcagac   2640

agtggttcaa agtttttttc ttccatttca ggtgtcgtga ggaattagcg gatccgccac   2700

catgaacatt aacgacctga ttcgggaaat aaagaacaag gactacacgg tcaagctgtc   2760

aggcaccgac tccaactcta taacacagct cattataagg gttaataatg atggcaacga   2820

atatgtcatc tctgaatccg agaatgaatc aatcgtggag aaattcatca gtgcatttaa   2880

aaacggctgg aaccaggagt acgaagatga ggaagagttc tacaatgata tgcaaactat   2940

cacactgaaa tctgagctga actagctcga gcggccgcca ctgtgctgga tatctgcaga   3000

attacaaaca ccattgtcac actccattat atacaaacac cattgtcaca ctccatagct   3060

taagtttaaa ccgctgatca gcctcgactg tgccttctag ttgccagcca tctgttgttt   3120

gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac tcccactgtc ctttcctaat   3180

aaaatgagga aattgcatcg cattgtctga gtaggtgtca ttctattctg gggggtgggg   3240

tggggcagga cagcaagggg gaggattggg aagacaatag caggcatgct ggggatgcgg   3300

tgggctctat ggtcgacgat atcagatcta ggaaccccta gtgatggagt tggccactcc   3360

ctctctgcgc gctcgctcgc tcactgaggc cgcccgggca aagcccgggc gtcgggcgac   3420

ctttggtcgc ccggcctcag tgagcgagcg agcgcgcaga gagggagtgg cccccccccc   3480

cccccccccc tgcattctag agagctccaa ttcgccctat agtgagtcgt attacgcgcg   3540

ctcactggcc gtcgttttac aacgtcgtga ctgggaaaac cctggcgtta cccaacttaa   3600

tcgccttgca gcacatcccc ctttcgccag ctggcgtaat agcgaagagg cccgcaccga   3660

tcgcccttcc caacagttgc gcagcctgaa tggcgaatgg gacgcgccct gtagcggcgc   3720

attaagcgcg gcgggtgtgg tggttacgcg cagcgtgacc gctacacttg ccagcgccct   3780

agcgcccgct cctttcgctt tcttcccttc ctttctcgcc acgttcgccg gctttccccg   3840

tcaagctcta aatcgggggc tccctttagg gttccgattt agtgctttac ggcacctcga   3900

ccccaaaaaa cttgattagg gtgatggttc acgtagtggg ccatcgccct gatagacggt   3960

ttttcgccct ttgacgttgg agtccacgtt ctttaatagt ggactcttgt tccaaactgg   4020

aacaacactc aaccctatct cggtctattc ttttgattta taagggattt tgccgatttc   4080

ggcctattgg ttaaaaaatg agctgattta acaaaaattt aacgcgaatt ttaacaaaat   4140

attaacgctt acaatttagg tggcactttt cggggaaatg tgcgcggaac ccctatttgt   4200

ttatttttct aaatacattc aaatatgtat ccgctcatga gacaataacc ctgataaatg   4260

cttcaataat attgaaaaag gaagagtatg agtattcaac atttccgtgt cgcccttatt   4320

cccttttttg cggcattttg ccttcctgtt tttgctcacc cagaaacgct ggtgaaagta   4380

aaagatgctg aagatcagtt gggtgcacga gtgggttaca tcgaactgga tctcaacagc   4440

ggtaagatcc ttgagagttt tcgccccgaa gaacgttttc caatgatgag cacttttaaa   4500

gttctgctat gtggcgcggt attatcccgt attgacgccg ggcaagagca actcggtcgc   4560

cgcatacact attctcagaa tgacttggtt gagtactcac cagtcacaga aaagcatctt   4620

acggatggca tgacagtaag agaattatgc agtgctgcca taaccatgag tgataacact   4680

gcggccaact tacttctgac aacgatcgga ggaccgaagg agctaaccgc ttttttgcac   4740

aacatggggg atcatgtaac tcgccttgat cgttgggaac cggagctgaa tgaagccata   4800

ccaaacgacg agcgtgacac cacgatgcct gtagcaatgg caacaacgtt gcgcaaacta   4860

ttaactggcg aactacttac tctagcttcc cggcaacaat taatagactg gatggaggcg   4920

gataaagttg caggaccact tctgcgctcg gcccttccgg ctggctggtt tattgctgat   4980

aaatctggag ccggtgagcg tgggtctcgc ggtatcattg cagcactggg gccagatggt   5040

aagccctccc gtatcgtagt tatctacacg acggggagtc aggcaactat ggatgaacga   5100

aatagacaga tcgctgagat aggtgcctca ctgattaagc attggtaact gtcagaccaa   5160

gtttactcat atatacttta gattgattta aaacttcatt tttaatttaa aaggatctag   5220

gtgaagatcc tttttgataa tctcatgacc aaaatccctt aacgtgagtt ttcgttccac   5280

tgagcgtcag accccgtaga aa                                            5302


<210>  11
<211>  4693
<212>  DNA
<213>  Artificial

<220>
<223>  U6-scaffold_EFS-AcrIIA4-scaffold-BGH (AAV construct)

<400>  11
ctaaattgta agcgttaata ttttgttaaa attcgcgtta aatttttgtt aaatcagctc     60

attttttaac caataggccg aaatcggcaa aatcccttat aaatcaaaag aatagaccga    120

gatagggttg agtgttgttc cagtttggaa caagagtcca ctattaaaga acgtggactc    180

caacgtcaaa gggcgaaaaa ccgtctatca gggcgatggc ccactacgtg aaccatcacc    240

ctaatcaagt tttttggggt cgaggtgccg taaagcacta aatcggaacc ctaaagggag    300

cccccgattt agagcttgac ggggaaagcc ggcgaacgtg gcgagaaagg aagggaagaa    360

agcgaaagga gcgggcgcta gggcgctggc aagtgtagcg gtcacgctgc gcgtaaccac    420

cacacccgcc gcgcttaatg cgccgctaca gggcgcgtcc cattcgccat tcaggctgcg    480

caactgttgg gaagggcgat cggtgcgggc ctcttcgcta ttacgccagc tggcgaaagg    540

gggatgtgct gcaaggcgat taagttgggt aacgccaggg ttttcccagt cacgacgttg    600

taaaacgacg gccagtgagc gcgcgtaata cgactcacta tagggcgaat tggagctctc    660

tagaatgcag gggggggggg gggggggggc cactccctct ctgcgcgctc gctcgctcac    720

tgaggccggg cgaccaaagg tcgcccgacg cccgggcttt gcccgggcgg cctcagtgag    780

cgagcgagcg cgcagagagg gagtggccaa ctccatcact aggggttcct agatctgata    840

tcgtcgacca tagagcccac cgcatcccca gcatgcctgc tattgtcttc ccaatcctcc    900

cccttgctgt cctgccccac cccacccccc agaatagaat gacacctact cagacaatgc    960

gatgcaattt cctcatttta ttaggaaagg acagtgggag tggcaccttc cagggtcaag   1020

gaaggcacgg gggaggggca aacaacagat ggctggcaac tagaaggcac agtcgaggct   1080

gatcagcggt ttaaacttaa gctagagacg acttcaacat caacggtata taaacttcaa   1140

catcaacggc gtctctaatt ctgcagatat ccagcacagt ggcggccgct cgagctagtt   1200

cagctcagat ttcagtgtga tagtttgcat atcattgtag aactcttcct catcttcgta   1260

ctcctggttc cagccgtttt taaatgcact gatgaatttc tccacgattg attcattctc   1320

ggattcagag atgacatatt cgttgccatc attattaacc cttataatga gctgtgttat   1380

agagttggag tcggtgcctg acagcttgac cgtgtagtcc ttgttcttta tttcccgaat   1440

caggtcgtta atgttcatgg tggcggatcc ctgtgttctg gcggcaaacc cgttgcgaaa   1500

aagaacgttc acggcgacta ctgcacttat atacggttct cccccaccct cgggaaaaag   1560

gcggagccag tacacgacat cactttccca gtttaccccg cgccaccttc tctaggcacc   1620

ggatcaattg ccgacccctc cccccaactt ctcggggact gtgggcgatg tgcgctctgc   1680

ccactgacgg gcaccggagc ggccgcaaaa aaagcaccga ctcggtgcca ctttttcaag   1740

ttgataacgg actagcctta tttaaacttg ctatgctgtt tccagcatag ctcttaaacc   1800

tgtcttcctc gaagactcgg tgtttcgtcc tttccacaag atatataaag ccaagaaatc   1860

gaaatacttt caagttacgg taagcatatg atagtccatt ttaaaacata attttaaaac   1920

tgcaaactac ccaagaaatt attactttct acgtcacgta ttttgtacta atatctttgt   1980

gtttacagtc aaattaattc taattatctc tctaacagcc ttgtatcgta tatgcaaata   2040

tgaaggaatc atgggaaata ggccctcttc ctgcccgacc ttggcgcgcg ctcggcgcgc   2100

ggtcacgctc cgtcacgtgg tgcgttttgc ctgcgcgtct ttccactggg gccggggcgg   2160

cgcggagggt tcagacgcgg gctcttactc aaacgctgat ccccgaaact accgagcagt   2220

gtctgcgcga cgcgaaagca tttttggagc gaggggccat ggtgcccatg ggattcccac   2280

gggtgttgga ctcgggcgcg ccgatatcag atctggcaaa cctagatgat ggaggtaccc   2340

actccctcta tgcgcgctcg ctcactcact cggccctgcc ggccagaggc cggcagtctg   2400

gagacctttg gtctccaggg ccgagtgagt gagcgagcgc gcatagaggg agtgggtagg   2460

acgcgtcctg caggatgcat actagtggta cccagctttt gttcccttta gtgagggtta   2520

attgcgcgct tggcgtaatc atggtcatag ctgtttcctg tgtgaaattg ttatccgctc   2580

acaattccac acaacatacg agccggaagc ataaagtgta aagcctgggg tgcctaatga   2640

gtgagctaac tcacattaat tgcgttgcgc tcactgcccg ctttccagtc gggaaacctg   2700

tcgtgccagc tgcattaatg aatcggccaa cgcgcgggga gaggcggttt gcgtattggg   2760

cgctcttccg cttcctcgct cactgactcg ctgcgctcgg tcgttcggct gcggcgagcg   2820

gtatcagctc actcaaaggc ggtaatacgg ttatccacag aatcagggga taacgcagga   2880

aagaacatgt gagcaaaagg ccagcaaaag gccaggaacc gtaaaaaggc cgcgttgctg   2940

gcgtttttcc ataggctccg cccccctgac gagcatcaca aaaatcgacg ctcaagtcag   3000

aggtggcgaa acccgacagg actataaaga taccaggcgt ttccccctgg aagctccctc   3060

gtgcgctctc ctgttccgac cctgccgctt accggatacc tgtccgcctt tctcccttcg   3120

ggaagcgtgg cgctttctca tagctcacgc tgtaggtatc tcagttcggt gtaggtcgtt   3180

cgctccaagc tgggctgtgt gcacgaaccc cccgttcagc ccgaccgctg cgccttatcc   3240

ggtaactatc gtcttgagtc caacccggta agacacgact tatcgccact ggcagcagcc   3300

actggtaaca ggattagcag agcgaggtat gtaggcggtg ctacagagtt cttgaagtgg   3360

tggcctaact acggctacac tagaaggaca gtatttggta tctgcgctct gctgaagcca   3420

gttaccttcg gaaaaagagt tggtagctct tgatccggca aacaaaccac cgctggtagc   3480

ggtggttttt ttgtttgcaa gcagcagatt acgcgcagaa aaaaaggatc tcaagaagat   3540

cctttgatct tttctacggg gtctgacgct cagtggaacg aaaactcacg ttaagggatt   3600

ttggtcatga gattatcaaa aaggatcttc acctagatcc ttttaaatta aaaatgaagt   3660

tttaaatcaa tctaaagtat atatgagtaa acttggtctg acagttacca atgcttaatc   3720

agtgaggcac ctatctcagc gatctgtcta tttcgttcat ccatagttgc ctgactcccc   3780

gtcgtgtaga taactacgat acgggagggc ttaccatctg gccccagtgc tgcaatgata   3840

ccgcgagacc cacgctcacc ggctccagat ttatcagcaa taaaccagcc agccggaagg   3900

gccgagcgca gaagtggtcc tgcaacttta tccgcctcca tccagtctat taattgttgc   3960

cgggaagcta gagtaagtag ttcgccagtt aatagtttgc gcaacgttgt tgccattgct   4020

acaggcatcg tggtgtcacg ctcgtcgttt ggtatggctt cattcagctc cggttcccaa   4080

cgatcaaggc gagttacatg atcccccatg ttgtgcaaaa aagcggttag ctccttcggt   4140

cctccgatcg ttgtcagaag taagttggcc gcagtgttat cactcatggt tatggcagca   4200

ctgcataatt ctcttactgt catgccatcc gtaagatgct tttctgtgac tggtgagtac   4260

tcaaccaagt cattctgaga atagtgtatg cggcgaccga gttgctcttg cccggcgtca   4320

atacgggata ataccgcgcc acatagcaga actttaaaag tgctcatcat tggaaaacgt   4380

tcttcggggc gaaaactctc aaggatctta ccgctgttga gatccagttc gatgtaaccc   4440

actcgtgcac ccaactgatc ttcagcatct tttactttca ccagcgtttc tgggtgagca   4500

aaaacaggaa ggcaaaatgc cgcaaaaaag ggaataaggg cgacacggaa atgttgaata   4560

ctcatactct tcctttttca atattattga agcatttatc agggttattg tctcatgagc   4620

ggatacatat ttgaatgtat ttagaaaaat aaacaaatag gggttccgcg cacatttccc   4680

cgaaaagtgc cac                                                      4693


<210>  12
<211>  4693
<212>  DNA
<213>  Artificial

<220>
<223>  U6-scaffold_EFS-AcrIIA4-2xmir122BS-BGH (AAV construct)

<400>  12
ctaaattgta agcgttaata ttttgttaaa attcgcgtta aatttttgtt aaatcagctc     60

attttttaac caataggccg aaatcggcaa aatcccttat aaatcaaaag aatagaccga    120

gatagggttg agtgttgttc cagtttggaa caagagtcca ctattaaaga acgtggactc    180

caacgtcaaa gggcgaaaaa ccgtctatca gggcgatggc ccactacgtg aaccatcacc    240

ctaatcaagt tttttggggt cgaggtgccg taaagcacta aatcggaacc ctaaagggag    300

cccccgattt agagcttgac ggggaaagcc ggcgaacgtg gcgagaaagg aagggaagaa    360

agcgaaagga gcgggcgcta gggcgctggc aagtgtagcg gtcacgctgc gcgtaaccac    420

cacacccgcc gcgcttaatg cgccgctaca gggcgcgtcc cattcgccat tcaggctgcg    480

caactgttgg gaagggcgat cggtgcgggc ctcttcgcta ttacgccagc tggcgaaagg    540

gggatgtgct gcaaggcgat taagttgggt aacgccaggg ttttcccagt cacgacgttg    600

taaaacgacg gccagtgagc gcgcgtaata cgactcacta tagggcgaat tggagctctc    660

tagaatgcag gggggggggg gggggggggc cactccctct ctgcgcgctc gctcgctcac    720

tgaggccggg cgaccaaagg tcgcccgacg cccgggcttt gcccgggcgg cctcagtgag    780

cgagcgagcg cgcagagagg gagtggccaa ctccatcact aggggttcct agatctgata    840

tcgtcgacca tagagcccac cgcatcccca gcatgcctgc tattgtcttc ccaatcctcc    900

cccttgctgt cctgccccac cccacccccc agaatagaat gacacctact cagacaatgc    960

gatgcaattt cctcatttta ttaggaaagg acagtgggag tggcaccttc cagggtcaag   1020

gaaggcacgg gggaggggca aacaacagat ggctggcaac tagaaggcac agtcgaggct   1080

gatcagcggt ttaaacttaa gctatggagt gtgacaatgg tgtttgtata taatggagtg   1140

tgacaatggt gtttgtaatt ctgcagatat ccagcacagt ggcggccgct cgagctagtt   1200

cagctcagat ttcagtgtga tagtttgcat atcattgtag aactcttcct catcttcgta   1260

ctcctggttc cagccgtttt taaatgcact gatgaatttc tccacgattg attcattctc   1320

ggattcagag atgacatatt cgttgccatc attattaacc cttataatga gctgtgttat   1380

agagttggag tcggtgcctg acagcttgac cgtgtagtcc ttgttcttta tttcccgaat   1440

caggtcgtta atgttcatgg tggcggatcc ctgtgttctg gcggcaaacc cgttgcgaaa   1500

aagaacgttc acggcgacta ctgcacttat atacggttct cccccaccct cgggaaaaag   1560

gcggagccag tacacgacat cactttccca gtttaccccg cgccaccttc tctaggcacc   1620

ggatcaattg ccgacccctc cccccaactt ctcggggact gtgggcgatg tgcgctctgc   1680

ccactgacgg gcaccggagc ggccgcaaaa aaagcaccga ctcggtgcca ctttttcaag   1740

ttgataacgg actagcctta tttaaacttg ctatgctgtt tccagcatag ctcttaaacc   1800

tgtcttcctc gaagactcgg tgtttcgtcc tttccacaag atatataaag ccaagaaatc   1860

gaaatacttt caagttacgg taagcatatg atagtccatt ttaaaacata attttaaaac   1920

tgcaaactac ccaagaaatt attactttct acgtcacgta ttttgtacta atatctttgt   1980

gtttacagtc aaattaattc taattatctc tctaacagcc ttgtatcgta tatgcaaata   2040

tgaaggaatc atgggaaata ggccctcttc ctgcccgacc ttggcgcgcg ctcggcgcgc   2100

ggtcacgctc cgtcacgtgg tgcgttttgc ctgcgcgtct ttccactggg gccggggcgg   2160

cgcggagggt tcagacgcgg gctcttactc aaacgctgat ccccgaaact accgagcagt   2220

gtctgcgcga cgcgaaagca tttttggagc gaggggccat ggtgcccatg ggattcccac   2280

gggtgttgga ctcgggcgcg ccgatatcag atctggcaaa cctagatgat ggaggtaccc   2340

actccctcta tgcgcgctcg ctcactcact cggccctgcc ggccagaggc cggcagtctg   2400

gagacctttg gtctccaggg ccgagtgagt gagcgagcgc gcatagaggg agtgggtagg   2460

acgcgtcctg caggatgcat actagtggta cccagctttt gttcccttta gtgagggtta   2520

attgcgcgct tggcgtaatc atggtcatag ctgtttcctg tgtgaaattg ttatccgctc   2580

acaattccac acaacatacg agccggaagc ataaagtgta aagcctgggg tgcctaatga   2640

gtgagctaac tcacattaat tgcgttgcgc tcactgcccg ctttccagtc gggaaacctg   2700

tcgtgccagc tgcattaatg aatcggccaa cgcgcgggga gaggcggttt gcgtattggg   2760

cgctcttccg cttcctcgct cactgactcg ctgcgctcgg tcgttcggct gcggcgagcg   2820

gtatcagctc actcaaaggc ggtaatacgg ttatccacag aatcagggga taacgcagga   2880

aagaacatgt gagcaaaagg ccagcaaaag gccaggaacc gtaaaaaggc cgcgttgctg   2940

gcgtttttcc ataggctccg cccccctgac gagcatcaca aaaatcgacg ctcaagtcag   3000

aggtggcgaa acccgacagg actataaaga taccaggcgt ttccccctgg aagctccctc   3060

gtgcgctctc ctgttccgac cctgccgctt accggatacc tgtccgcctt tctcccttcg   3120

ggaagcgtgg cgctttctca tagctcacgc tgtaggtatc tcagttcggt gtaggtcgtt   3180

cgctccaagc tgggctgtgt gcacgaaccc cccgttcagc ccgaccgctg cgccttatcc   3240

ggtaactatc gtcttgagtc caacccggta agacacgact tatcgccact ggcagcagcc   3300

actggtaaca ggattagcag agcgaggtat gtaggcggtg ctacagagtt cttgaagtgg   3360

tggcctaact acggctacac tagaaggaca gtatttggta tctgcgctct gctgaagcca   3420

gttaccttcg gaaaaagagt tggtagctct tgatccggca aacaaaccac cgctggtagc   3480

ggtggttttt ttgtttgcaa gcagcagatt acgcgcagaa aaaaaggatc tcaagaagat   3540

cctttgatct tttctacggg gtctgacgct cagtggaacg aaaactcacg ttaagggatt   3600

ttggtcatga gattatcaaa aaggatcttc acctagatcc ttttaaatta aaaatgaagt   3660

tttaaatcaa tctaaagtat atatgagtaa acttggtctg acagttacca atgcttaatc   3720

agtgaggcac ctatctcagc gatctgtcta tttcgttcat ccatagttgc ctgactcccc   3780

gtcgtgtaga taactacgat acgggagggc ttaccatctg gccccagtgc tgcaatgata   3840

ccgcgagacc cacgctcacc ggctccagat ttatcagcaa taaaccagcc agccggaagg   3900

gccgagcgca gaagtggtcc tgcaacttta tccgcctcca tccagtctat taattgttgc   3960

cgggaagcta gagtaagtag ttcgccagtt aatagtttgc gcaacgttgt tgccattgct   4020

acaggcatcg tggtgtcacg ctcgtcgttt ggtatggctt cattcagctc cggttcccaa   4080

cgatcaaggc gagttacatg atcccccatg ttgtgcaaaa aagcggttag ctccttcggt   4140

cctccgatcg ttgtcagaag taagttggcc gcagtgttat cactcatggt tatggcagca   4200

ctgcataatt ctcttactgt catgccatcc gtaagatgct tttctgtgac tggtgagtac   4260

tcaaccaagt cattctgaga atagtgtatg cggcgaccga gttgctcttg cccggcgtca   4320

atacgggata ataccgcgcc acatagcaga actttaaaag tgctcatcat tggaaaacgt   4380

tcttcggggc gaaaactctc aaggatctta ccgctgttga gatccagttc gatgtaaccc   4440

actcgtgcac ccaactgatc ttcagcatct tttactttca ccagcgtttc tgggtgagca   4500

aaaacaggaa ggcaaaatgc cgcaaaaaag ggaataaggg cgacacggaa atgttgaata   4560

ctcatactct tcctttttca atattattga agcatttatc agggttattg tctcatgagc   4620

ggatacatat ttgaatgtat ttagaaaaat aaacaaatag gggttccgcg cacatttccc   4680

cgaaaagtgc cac                                                      4693


<210>  13
<211>  7475
<212>  DNA
<213>  Artificial

<220>
<223>  N-Cas9-Intein_U6short-scaffold (AAV construct)

<400>  13
ggccgcggaa tgtgtgtcag ttagggtgtg gaaagtcccc aggctcccca gcaggcagaa     60

gtatgcaaag catgcatctc aattagtcag caaccagtcc cggtctcctc ccatgcatgt    120

caatattggc cattagccat attattcatt ggttatatag cataaatcaa tattggctat    180

tggccattgc atacgttgta tctatatcat aatatgtaca tttatattgg ctcatgtcca    240

atatgaccgc catgttggca ttgattattg actagttatt aatagtaatc aattacgggg    300

tcattagttc atagcccata tatggagttc cgcgttacat aacttacggt aaatggcccg    360

cctggctgac cgcccaacga cccccgccca ttgacgtcaa taatgacgta tgttcccata    420

gtaacgccaa tagggacttt ccattgacgt caatgggtgg agtatttacg gtaaactgcc    480

cacttggcag tacatcaagt gtatcatatg ccaagtccgc cccctattga cgtcaatgac    540

ggtaaatggc ccgcctggca ttatgcccag tacatgacct tacgggactt tcctacttgg    600

cagtacatct acgtattagt catcgctatt accatggtga tgcggttttg gcagtacacc    660

aatgggcgtg gatagcggtt tgactcacgg ggatttccaa gtctccaccc cattgacgtc    720

aatgggagtt tgttttggca ccaaaatcaa cgggactttc caaaatgtcg taataacccc    780

gccccgttga cgcaaatggg cggtaggcgt gtacggtggg aggtctatat aagcagaggt    840

cgtttagtga accgtcagat cactagtagc tttattgcgg tagtttatca cagttaaatt    900

gctaacgcag tcagtgctcg actgatcaca ggtaagtatc aaggttacaa gacaggttta    960

aggaggccaa tagaaactgg gcttgtcgag acagagaaga ttcttgcgtt tctgataggc   1020

acctattggt cttactgaca tccactttgc ctttctctcc acaggggtac cgaagccgct   1080

agcgctaccg gtcgccacca tggccccaaa gaagaagcgg aaggtcggta tccacggagt   1140

cccagcagcc gacaagaagt actccattgg gctcgatatc ggcacaaaca gcgtcggctg   1200

ggccgtcatt acggacgagt acaaggtgcc gagcaaaaaa ttcaaagttc tgggcaatac   1260

cgatcgccac agcataaaga agaacctcat tggcgccctc ctgttcgact ccggggaaac   1320

ggccgaagcc acgcggctca aaagaacagc acggcgcaga tatacccgca gaaagaatcg   1380

gatctgctac ctgcaggaga tctttagtaa tgagatggct aaggtggatg actctttctt   1440

ccataggctg gaggagtcct ttttggtgga ggaggataaa aagcacgagc gccacccaat   1500

ctttggcaat atcgtggacg aggtggcgta ccatgaaaag tacccaacca tatatcatct   1560

gaggaagaag cttgtagaca gtactgataa ggctgacttg cggttgatct atctcgcgct   1620

ggcgcatatg atcaaatttc ggggacactt cctcatcgag ggggacctga acccagacaa   1680

cagcgatgtc gacaaactct ttatccaact ggttcagact tacaatcagc ttttcgaaga   1740

gaacccgatc aacgcatccg gagttgacgc caaagcaatc ctgagcgcta ggctgtccaa   1800

atcccggcgg ctcgaaaacc tcatcgcaca gctccctggg gagaagaaga acggcctgtt   1860

tggtaatctt atcgccctgt cactcgggct gacccccaac tttaaatcta acttcgacct   1920

ggccgaagat gccaagcttc aactgagcaa agacacctac gatgatgatc tcgacaatct   1980

gctggcccag atcggcgacc agtacgcaga cctttttttg gcggcaaaga acctgtcaga   2040

cgccattctg ctgagtgata ttctgcgagt gaacacggag atcaccaaag ctccgctgag   2100

cgctagtatg atcaagcgct atgatgagca ccaccaagac ttgactttgc tgaaggccct   2160

tgtcagacag caactgcctg agaagtacaa ggaaattttc ttcgatcagt ctaaaaatgg   2220

ctacgccgga tacattgacg gcggagcaag ccaggaggaa ttttacaaat ttattaagcc   2280

catcttggaa aaaatggacg gcaccgagga gctgctggta aagcttaaca gagaagatct   2340

gttgcgcaaa cagcgcactt tcgacaatgg aagcatcccc caccagattc acctgggcga   2400

actgcacgct atcctcaggc ggcaagagga tttctacccc tttttgaaag ataacaggga   2460

aaagattgag aaaatcctca catttcggat accctactat gtaggccccc tcgcccgggg   2520

aaattccaga ttcgcgtgga tgactcgcaa atcagaagag accatcactc cctggaactt   2580

cgaggaagtc gtggataagg gggcctctgc ccagtccttc atcgaaagga tgactaactt   2640

tgataaaaat ctgcctaacg aaaaggtgct tcctaaacac tctctgctgt acgagtactt   2700

cacagtttat aacgagctca ccaaggtcaa atacgtcaca gaagggatga gaaagccagc   2760

attcctgtct ggagagcaga agaaagctat cgtggacctc ctcttcaaga cgaaccggaa   2820

agttaccgtg aaacagctca aagaagacta tttcaaaaag attgaatgtt tcgactctgt   2880

tgaaatcagc ggagtggagg atcgcttcaa cgcatccctg ggaacgtatc acgatctcct   2940

gaaaatcatt aaagacaagg acttcctgga caatgaggag aacgaggaca ttcttgagga   3000

cattgtcctc acccttacgt tgtttgaaga tagggagatg attgaagaac gcttgaaaac   3060

ttacgctcat ctcttcgacg acaaagtcat gaaacagctc aagaggcgcc gatatacagg   3120

atgggggcgg ctgtcaagaa aactgatcaa tgggatccga gacaagcaga gtggaaagac   3180

aatcctggat tttcttaagt ccgatggatt tgccaaccgg aacttcatgc agttgatcca   3240

tgatgactct ctcaccttta aggaggacat ccagaaagca caagtttgtc tggctggcga   3300

tactctcatt accctggccg atggacgacg agtgcctatt agagaactgg tgtcacagca   3360

gaatttttcc gtgtgggctc tgaatcctca gacttaccgc ctggagaggg ctagagtgag   3420

tagagctttc tgtaccggca tcaaacctgt gtaccgcctc accactagac tggggagatc   3480

cattagggcc actgccaacc accgatttct cacacctcag ggctggaaac gagtcgatga   3540

actccagcct ggagattacc tggctctgcc taggagaatc cctactgcct cctgatctcg   3600

agctcgatga gtttggacaa accacaacta gaatgcagtg aaaaaaatgc tttatttgtg   3660

aaatttgtga tgctattgct ttatttgtaa ccattataag ctgcaataaa caagttaaca   3720

acaacaattg cattcatttt atgtttcagg ttcaggggga ggtgtgggag gttttttaaa   3780

gcaagtaaaa cctctacaaa tgtggtactt aagaggggga gaccaaaggg cacgcgttta   3840

aggcctcacg tgacatgtga gcaaaaggcc agcaaaatgt acaaaaaagc aggctttaaa   3900

ggaaccaatt cagtcgactg gatccggtac caaggtcggg caggaagagg gcctatttcc   3960

catgattcct tcatatttgc atatacgata caaggctgtt agagagataa ttagaattaa   4020

tttgactgta aacacaaaga tattagtaca aaatacgtga cgtagaaagt aataatttct   4080

tgggtagttt gcagttttaa aattatgttt taaaatggac tatcatatgc ttaccgtaac   4140

ttgaaagtat ttcgatttct tggctttata tatcttgtgg aaaggacgaa acaccagaga   4200

cgacttcaac atcaacggcg tctctgtttt agagctagaa atagcaagtt aaaataaggc   4260

tagtccgtta tcaacttgaa aaagtggcac cgagtcggtg cttttttttc tagagggcgg   4320

ccgcaggtag ataagtagca tggcgggtta atcattaact acaaggaacc cctagtgatg   4380

gagttggcca ctccctctct gcgcgctcgc tcgctcactg aggccgggcg accaaaggtc   4440

gcccgacgcc cgggctttgc ccgggcggcc tcagtgagcg agcgagcgcg cagccttaat   4500

taaatctggc gtaatcatgg tcatagctgt ttcctgtgtg aaattgttat ccgctcacaa   4560

ttccacacaa catacgagcc ggaagcataa agtgtaaagc ctggggtgcc taatgagtga   4620

gctaactcac attaattgcg ttgcgctcac tgcccgcttt ccagtcggga aacctgtcgt   4680

gccagctgca ttaatgaatc ggccaacgcg cggggagagg cggtttgcgt attgggcgct   4740

cttccgcttc ctcgctcact gactcgctgc gctcggtcgt tcggctgcgg cgagcggtat   4800

cagctcactc aaaggcggta atacggttat ccacagaatc aggggataac gcaggaaaga   4860

acatgtgagc aaaaccgcag caaaaggcca ggaaccgtaa aaaggccgcg ttgctggcgt   4920

ttttccatag gctccgcccc cctgacgagc atcacaaaaa tcgacgctca agtcagaggt   4980

ggcgaaaccc gacaggacta taaagatacc aggcgtttcc ccctggaagc tccctcgtgc   5040

gctctcctgt tccgaccctg ccgcttaccg gatacctgtc cgcctttctc ccttcgggaa   5100

gcgtggcgct ttctcatagc tcacgctgta ggtatctcag ttcggtgtag gtcgttcgct   5160

ccaagctggg ctgtgtgcac gaaccccccg ttcagcccga ccgctgcgcc ttatccggta   5220

actatcgtct tgagtccaac ccggtaagac acgacttatc gccactggca gcagccactg   5280

gtaacaggat tagcagagcg aggtatgtag gcggtgctac agagttcttg aagtggtggc   5340

ctaactacgg ctacactaga aggacagtat ttggtatctg cgctctgctg aagccagtta   5400

ccttcggaaa aagagttggt agctcttgat ccggcaaaca aaccaccgct ggtagcggtg   5460

gtttttttgt ttgcaagcag cagattacgc gcagaaaaaa aggatctcaa gaagatcctt   5520

tgatcttttc tacggggtct gacgctcagt ggaacgaaaa ctcacgttaa gggattttgg   5580

tcatgagatt atcaaaaagg atcttcacct agatcctttt aaattaaaaa tgaagtttta   5640

aatcaatcta aagtatatat gagtaaactt ggtctgacag ttaccaatgc ttaatcagtg   5700

aggcacctat ctcagcgatc tgtctatttc gttcatccat agttgcctga ctccccgtcg   5760

tgtagataac tacgatacgg gagggcttac catctggccc cagtgctgca atgataccgc   5820

gagacccacg ctcaccggct ccagatttat cagcaataaa ccagccagcc ggaagggccg   5880

agcgcagaag tggtcctgca actttatccg cctccatcca gtctattaat tgttgccggg   5940

aagctagagt aagtagttcg ccagttaata gtttgcgcaa cgttgttacc attactacag   6000

gcatcgtggt gtcacgctcg tcgtttggta tggcttcatt cagctccggt tcccaacgat   6060

caaggcgagt tacatgatcc cccatgttgt gcaaaaaagc ggttagctcc ttcggtcctc   6120

cgatcgttgt cagaagtaag ttggccgcag tgttatcact catggttatg gcagcactgc   6180

ataattctct tactgtcatg ccatccgtaa gatgcttttc tgtgactggt gagtactcaa   6240

ccaagtcatt ctgagaatag tgtatgcggc gaccgagttg ctcttgcccg gcgtcaatac   6300

gggataatac cgcgccacat agcagaactt taaaagtgct catcattgga aaacgttctt   6360

cggggcgaaa actctcaagg atcttaccac tattgagatc cagttcgatg taacccactc   6420

gtgcacccaa ctgatcttca gcatctttta ctttcaccag cgtttctggg tgagcaaaaa   6480

caggaaggca aaatgccgca aaaaagggaa taagggcgac acggaaatgt tgaatactca   6540

tactcttcct ttttcaatat tattgaagca tttatcaggg ttattgtctc atgagcggat   6600

acatatttga atgtatttag aaaaataaac aaataggggt tccgcgcaca tttccccgaa   6660

agatgccacc tgaaattata aacgttaata ttttgttaaa attcgcgtta aatttttgtt   6720

aaatcagctc attttttaac caataggccg aaatcggcaa aatcccttat aaatcaaaag   6780

aatagaccga gatagggttg agtgttgttc cagtttggaa caagagtcca ctattaaaga   6840

acgtggactc caacgtcaaa gggcgaaaaa ccgtctatca gggcgatggc ccactacgtg   6900

aaccatcacc ctaatcaagt tttttggggt cgaggtgccg taaagcacta aatcggaacc   6960

ctaaagggag cccccgattt agagcttgac ggggaaagcc ggcgaacgtg gcgagaaagg   7020

aagggaagaa agcgaaagga gcgggcgcta gggcgctggc aagtgtagcg gtcacgctgc   7080

gcgtaaccac cacacccgcc gcgcttaatg cgccgctaca gggcgcgtcc cattcgccat   7140

tcaggctgcg caactgttgg gaagggcgat cggtgcgggc ctcttcgcta ttacgccagc   7200

tggcgaaagg gggatgtgct gcaaggcgat taagttgggt aacgccaggg ttttcccagt   7260

cacgacgttg taaaacgacg gccagtgaat taggttaatt aaggctgcgc gctcgctcgc   7320

tcactgaggc cgcccgggca aagcccgggc gtcgggcgac ctttggtcgc ccggcctcag   7380

tgagcgagcg agcgcgcaga gagggagtgg ccaactccat cactaggggt tccttgtagt   7440

taatgattaa cccgccatgc tacttatcta cctgc                              7475


<210>  14
<211>  7930
<212>  DNA
<213>  Artificial

<220>
<223>  C-Cas9-Intein_CMV-AcrIIA4-scaffold-BGH (AAV construct)

<400>  14
ggccgccatt atggaatgtg tgtcagttag ggtgtggaaa gtccccaggc tccccagcag     60

gcagaagtat gcaaagcatg catctcaatt agtcagcaac cagtcccggt ctcctcccat    120

gcatgtcaat attggccatt agccatatta ttcattggtt atatagcata aatcaatatt    180

ggctattggc cattgcatac gttgtatcta tatcataata tgtacattta tattggctca    240

tgtccaatat gaccgccatg ttggcattga ttattgacta gttattaata gtaatcaatt    300

acggggtcat tagttcatag cccatatatg gagttccgcg ttacataact tacggtaaat    360

ggcccgcctg gctgaccgcc caacgacccc cgcccattga cgtcaataat gacgtatgtt    420

cccatagtaa cgccaatagg gactttccat tgacgtcaat gggtggagta tttacggtaa    480

actgcccact tggcagtaca tcaagtgtat catatgccaa gtccgccccc tattgacgtc    540

aatgacggta aatggcccgc ctggcattat gcccagtaca tgaccttacg ggactttcct    600

acttggcagt acatctacgt attagtcatc gctattacca tggtgatgcg gttttggcag    660

tacaccaatg ggcgtggata gcggtttgac tcacggggat ttccaagtct ccaccccatt    720

gacgtcaatg ggagtttgtt ttggcaccaa aatcaacggg actttccaaa atgtcgtaat    780

aaccccgccc cgttgacgca aatgggcggt aggcgtgtac ggtgggaggt ctatataagc    840

agaggtcgtt tagtgaaccg tcagatcact agtagcttta ttgcggtagt ttatcacagt    900

taaattgcta acgcagtcag tgctcgactg atcacaggta agtatcaagg ttacaagaca    960

ggtttaagga ggccaataga aactgggctt gtcgagacag agaagattct tgcgtttctg   1020

ataggcacct attggtctta ctgacatcca ctttgccttt ctctccacag gggtaccgaa   1080

gccgctagcg ctaccggtcg ccaccatggc ggcggcgtgc ccggaactgc gtcagctggc   1140

gcagagcgat gtgtattggg atccgattgt gagcattgaa ccggatggcg tggaagaagt   1200

gtttgatctg accgtgccgg gcccgcataa ctttgtggcg aacgatatta ttgcgcataa   1260

ctctggccag ggggacagtc ttcacgagca catcgctaat cttgcaggta gcccagctat   1320

caaaaaggga atactgcaga ccgttaaggt cgtggatgaa ctcgtcaaag taatgggaag   1380

gcataagccc gagaatatcg ttatcgagat ggcccgagag aaccaaacta cccagaaggg   1440

acagaagaac agtagggaaa ggatgaagag gattgaagag ggtataaaag aactggggtc   1500

ccaaatcctt aaggaacacc cagttgaaaa cacccagctt cagaatgaga agctctacct   1560

gtactacctg cagaacggca gggacatgta cgtggatcag gaactggaca tcaatcggct   1620

ctccgactac gacgtggatc atatcgtgcc ccagtctttt ctcaaagatg attctattga   1680

taataaagtg ttgacaagat ccgataaaaa tagagggaag agtgataacg tcccctcaga   1740

agaagttgtc aagaaaatga aaaattattg gcggcagctg ctgaacgcca aactgatcac   1800

acaacggaag ttcgataatc tgactaaggc tgaacgaggt ggcctgtctg agttggataa   1860

agccggcttc atcaaaaggc agcttgttga gacacgccag atcaccaagc acgtggccca   1920

aattctcgat tcacgcatga acaccaagta cgatgaaaat gacaaactga ttcgagaggt   1980

gaaagttatt actctgaagt ctaagctggt ctcagatttc agaaaggact ttcagtttta   2040

taaggtgaga gagatcaaca attaccacca tgcgcatgat gcctacctga atgcagtggt   2100

aggcactgca cttatcaaaa aatatcccaa gcttgaatct gaatttgttt acggagacta   2160

taaagtgtac gatgttagga aaatgatcgc aaagtctgag caggaaatag gcaaggccac   2220

cgctaagtac ttcttttaca gcaatattat gaattttttc aagaccgaga ttacactggc   2280

caatggagag attcggaagc gaccacttat cgaaacaaac ggagaaacag gagaaatcgt   2340

gtgggacaag ggtagggatt tcgcgacagt ccggaaggtc ctgtccatgc cgcaggtgaa   2400

catcgttaaa aagaccgaag tacagaccgg aggcttctcc aaggaaagta tcctcccgaa   2460

aaggaacagc gacaagctga tcgcacgcaa aaaagattgg gaccccaaga aatacggcgg   2520

attcgattct cctacagtcg cttacagtgt actggttgtg gccaaagtgg agaaagggaa   2580

gtctaaaaaa ctcaaaagcg tcaaggaact gctgggcatc acaatcatgg agcgatcaag   2640

cttcgaaaaa aaccccatcg actttctcga ggcgaaagga tataaagagg tcaaaaaaga   2700

cctcatcatt aagcttccca agtactctct ctttgagctt gaaaacggcc ggaaacgaat   2760

gctcgctagt gcgggcgagc tgcagaaagg taacgagctg gcactgccct ctaaatacgt   2820

taatttcttg tatctggcca gccactatga aaagctcaaa gggtctcccg aagataatga   2880

gcagaagcag ctgttcgtgg aacaacacaa acactacctt gatgagatca tcgagcaaat   2940

aagcgaattc tccaaaagag tgatcctcgc cgacgctaac ctcgataagg tgctttctgc   3000

ttacaataag cacagggata agcccatcag ggagcaggca gaaaacatta tccacttgtt   3060

tactctgacc aacttgggcg cgcctgcagc cttcaagtac ttcgacacca ccatagacag   3120

aaagcggtac acctctacaa aggaggtcct ggacgccaca ctgattcatc agtcaattac   3180

ggggctctat gaaacaagaa tcgacctctc tcagctcggt ggagacagca gggctgaccc   3240

caagaagaag aggaaggtgt ctcgagctcg atgagtttgg acaaaccaca actagaatgc   3300

agtgaaaaaa atgctttatt tgtgaaattt gtgatgctat tgctttattt gtaaccatta   3360

taagctgcaa taaacaagtt aacaacaaca attgcattca ttttatgttt caggttcagg   3420

gggaggtgtg ggaggttttt taaagcaagt aaaacctcta caaatgtggt atctagagac   3480

attgattatt gactagttat taatagtaat caattacggg gtcattagtt catagcccat   3540

atatggagtt ccgcgttaca taacttacgg taaatggccc gcctggctga ccgcccaacg   3600

acccccgccc attgacgtca ataatgacgt atgttcccat agtaacgcca atagggactt   3660

tccattgacg tcaatgggtg gagtatttac ggtaaactgc ccacttggca gtacatcaag   3720

tgtatcatat gccaagtacg ccccctattg acgtcaatga cggtaaatgg cccgcctggc   3780

attatgccca gtacatgacc ttatgggact ttcctacttg gcagtacatc tacgtattag   3840

tcatcgctat taccatggtg atgcggtttt ggcagtacat caatgggcgt ggatagcggt   3900

ttgactcacg gggatttcca agtctccacc ccattgacgt caatgggagt ttgttttggc   3960

accaaaatca acgggacttt ccaaaatgtc gtaacaactc cgccccattg acgcaaatgg   4020

gcggtaggcg tgtacggtgg gaggtctata taagcagagc tctctggcta actagagaac   4080

ccactgctta ctggcttatc gaaattaata cgactcacta tagggagacc caagctggct   4140

agcatgaaca ttaacgacct gattcgggaa ataaagaaca aggactacac ggtcaagctg   4200

tcaggcaccg actccaactc tataacacag ctcattataa gggttaataa tgatggcaac   4260

gaatatgtca tctctgaatc cgagaatgaa tcaatcgtgg agaaattcat cagtgcattt   4320

aaaaacggct ggaaccagga gtacgaagat gaggaagagt tctacaatga tatgcaaact   4380

atcacactga aatctgagct gaactagctc gagcggccgc cactgtgctg gatatctgca   4440

gaattagaga cgccgttgat gttgaagttt atataccgtt gatgttgaag tcgtctctag   4500

cttaagttta aaccgctgat cagcctcgac tgtgccttct agttgccagc catctgttgt   4560

ttgcccctcc cccgtgcctt ccttgaccct ggaaggtgcc actcccactg tcctttccta   4620

ataaaatgag gaaattgcat cgcattgtct gagtaggtgt cattctattc tggggggtgg   4680

ggtggggcag gacagcaagg gggaggattg ggaagacaat agcaggcatg ctggggatgc   4740

ggtgggctct atggacgcgt gcggccgcag gtagataagt agcatggcgg gttaatcatt   4800

aactacaagg aacccctagt gatggagttg gccactccct ctctgcgcgc tcgctcgctc   4860

actgaggccg ggcgaccaaa ggtcgcccga cgcccgggct ttgcccgggc ggcctcagtg   4920

agcgagcgag cgcgcagcct aattaaggcc ttaattaaat ctggcgtaat catggtcata   4980

gctgtttcct gtgtgaaatt gttatccgct cacaattcca cacaacatac gagccggaag   5040

cataaagtgt aaagcctggg gtgcctaatg agtgagctaa ctcacattaa ttgcgttgcg   5100

ctcactgccc gctttccagt cgggaaacct gtcgtgccag ctgcattaat gaatcggcca   5160

acgcgcgggg agaggcggtt tgcgtattgg gcgctcttcc gcttcctcgc tcactgactc   5220

gctgcgctcg gtcgttcggc tgcggcgagc ggtatcagct cactcaaagg cggtaatacg   5280

gttatccaca gaatcagggg ataacgcagg aaagaacatg tgagcaaaac cgcagcaaaa   5340

ggccaggaac cgtaaaaagg ccgcgttgct ggcgtttttc cataggctcc gcccccctga   5400

cgagcatcac aaaaatcgac gctcaagtca gaggtggcga aacccgacag gactataaag   5460

ataccaggcg tttccccctg gaagctccct cgtgcgctct cctgttccga ccctgccgct   5520

taccggatac ctgtccgcct ttctcccttc gggaagcgtg gcgctttctc atagctcacg   5580

ctgtaggtat ctcagttcgg tgtaggtcgt tcgctccaag ctgggctgtg tgcacgaacc   5640

ccccgttcag cccgaccgct gcgccttatc cggtaactat cgtcttgagt ccaacccggt   5700

aagacacgac ttatcgccac tggcagcagc cactggtaac aggattagca gagcgaggta   5760

tgtaggcggt gctacagagt tcttgaagtg gtggcctaac tacggctaca ctagaaggac   5820

agtatttggt atctgcgctc tgctgaagcc agttaccttc ggaaaaagag ttggtagctc   5880

ttgatccggc aaacaaacca ccgctggtag cggtggtttt tttgtttgca agcagcagat   5940

tacgcgcaga aaaaaaggat ctcaagaaga tcctttgatc ttttctacgg ggtctgacgc   6000

tcagtggaac gaaaactcac gttaagggat tttggtcatg agattatcaa aaaggatctt   6060

cacctagatc cttttaaatt aaaaatgaag ttttaaatca atctaaagta tatatgagta   6120

aacttggtct gacagttacc aatgcttaat cagtgaggca cctatctcag cgatctgtct   6180

atttcgttca tccatagttg cctgactccc cgtcgtgtag ataactacga tacgggaggg   6240

cttaccatct ggccccagtg ctgcaatgat accgcgagac ccacgctcac cggctccaga   6300

tttatcagca ataaaccagc cagccggaag ggccgagcgc agaagtggtc ctgcaacttt   6360

atccgcctcc atccagtcta ttaattgttg ccgggaagct agagtaagta gttcgccagt   6420

taatagtttg cgcaacgttg ttaccattac tacaggcatc gtggtgtcac gctcgtcgtt   6480

tggtatggct tcattcagct ccggttccca acgatcaagg cgagttacat gatcccccat   6540

gttgtgcaaa aaagcggtta gctccttcgg tcctccgatc gttgtcagaa gtaagttggc   6600

cgcagtgtta tcactcatgg ttatggcagc actgcataat tctcttactg tcatgccatc   6660

cgtaagatgc ttttctgtga ctggtgagta ctcaaccaag tcattctgag aatagtgtat   6720

gcggcgaccg agttgctctt gcccggcgtc aatacgggat aataccgcgc cacatagcag   6780

aactttaaaa gtgctcatca ttggaaaacg ttcttcgggg cgaaaactct caaggatctt   6840

accactattg agatccagtt cgatgtaacc cactcgtgca cccaactgat cttcagcatc   6900

ttttactttc accagcgttt ctgggtgagc aaaaacagga aggcaaaatg ccgcaaaaaa   6960

gggaataagg gcgacacgga aatgttgaat actcatactc ttcctttttc aatattattg   7020

aagcatttat cagggttatt gtctcatgag cggatacata tttgaatgta tttagaaaaa   7080

taaacaaata ggggttccgc gcacatttcc ccgaaagatg ccacctgaaa ttataaacgt   7140

taatattttg ttaaaattcg cgttaaattt ttgttaaatc agctcatttt ttaaccaata   7200

ggccgaaatc ggcaaaatcc cttataaatc aaaagaatag accgagatag ggttgagtgt   7260

tgttccagtt tggaacaaga gtccactatt aaagaacgtg gactccaacg tcaaagggcg   7320

aaaaaccgtc tatcagggcg atggcccact acgtgaacca tcaccctaat caagtttttt   7380

ggggtcgagg tgccgtaaag cactaaatcg gaaccctaaa gggagccccc gatttagagc   7440

ttgacgggga aagccggcga acgtggcgag aaaggaaggg aagaaagcga aaggagcggg   7500

cgctagggcg ctggcaagtg tagcggtcac gctgcgcgta accaccacac ccgccgcgct   7560

taatgcgccg ctacagggcg cgtcccattc gccattcagg ctgcgcaact gttgggaagg   7620

gcgatcggtg cgggcctctt cgctattacg ccagctggcg aaagggggat gtgctgcaag   7680

gcgattaagt tgggtaacgc cagggttttc ccagtcacga cgttgtaaaa cgacggccag   7740

tgaattaggt taattaaggc tgcgcgctcg ctcgctcact gaggccgccc gggcaaagcc   7800

cgggcgtcgg gcgacctttg gtcgcccggc ctcagtgagc gagcgagcgc gcagagaggg   7860

agtggccaac tccatcacta ggggttcctt gtagttaatg attaacccgc catgctactt   7920

atctacctgc                                                          7930


<210>  15
<211>  7930
<212>  DNA
<213>  Artificial

<220>
<223>  C-Cas9-Intein_CMV-AcrIIA4-2xmir122BS-BGH (AAV construct)

<400>  15
ggccgccatt atggaatgtg tgtcagttag ggtgtggaaa gtccccaggc tccccagcag     60

gcagaagtat gcaaagcatg catctcaatt agtcagcaac cagtcccggt ctcctcccat    120

gcatgtcaat attggccatt agccatatta ttcattggtt atatagcata aatcaatatt    180

ggctattggc cattgcatac gttgtatcta tatcataata tgtacattta tattggctca    240

tgtccaatat gaccgccatg ttggcattga ttattgacta gttattaata gtaatcaatt    300

acggggtcat tagttcatag cccatatatg gagttccgcg ttacataact tacggtaaat    360

ggcccgcctg gctgaccgcc caacgacccc cgcccattga cgtcaataat gacgtatgtt    420

cccatagtaa cgccaatagg gactttccat tgacgtcaat gggtggagta tttacggtaa    480

actgcccact tggcagtaca tcaagtgtat catatgccaa gtccgccccc tattgacgtc    540

aatgacggta aatggcccgc ctggcattat gcccagtaca tgaccttacg ggactttcct    600

acttggcagt acatctacgt attagtcatc gctattacca tggtgatgcg gttttggcag    660

tacaccaatg ggcgtggata gcggtttgac tcacggggat ttccaagtct ccaccccatt    720

gacgtcaatg ggagtttgtt ttggcaccaa aatcaacggg actttccaaa atgtcgtaat    780

aaccccgccc cgttgacgca aatgggcggt aggcgtgtac ggtgggaggt ctatataagc    840

agaggtcgtt tagtgaaccg tcagatcact agtagcttta ttgcggtagt ttatcacagt    900

taaattgcta acgcagtcag tgctcgactg atcacaggta agtatcaagg ttacaagaca    960

ggtttaagga ggccaataga aactgggctt gtcgagacag agaagattct tgcgtttctg   1020

ataggcacct attggtctta ctgacatcca ctttgccttt ctctccacag gggtaccgaa   1080

gccgctagcg ctaccggtcg ccaccatggc ggcggcgtgc ccggaactgc gtcagctggc   1140

gcagagcgat gtgtattggg atccgattgt gagcattgaa ccggatggcg tggaagaagt   1200

gtttgatctg accgtgccgg gcccgcataa ctttgtggcg aacgatatta ttgcgcataa   1260

ctctggccag ggggacagtc ttcacgagca catcgctaat cttgcaggta gcccagctat   1320

caaaaaggga atactgcaga ccgttaaggt cgtggatgaa ctcgtcaaag taatgggaag   1380

gcataagccc gagaatatcg ttatcgagat ggcccgagag aaccaaacta cccagaaggg   1440

acagaagaac agtagggaaa ggatgaagag gattgaagag ggtataaaag aactggggtc   1500

ccaaatcctt aaggaacacc cagttgaaaa cacccagctt cagaatgaga agctctacct   1560

gtactacctg cagaacggca gggacatgta cgtggatcag gaactggaca tcaatcggct   1620

ctccgactac gacgtggatc atatcgtgcc ccagtctttt ctcaaagatg attctattga   1680

taataaagtg ttgacaagat ccgataaaaa tagagggaag agtgataacg tcccctcaga   1740

agaagttgtc aagaaaatga aaaattattg gcggcagctg ctgaacgcca aactgatcac   1800

acaacggaag ttcgataatc tgactaaggc tgaacgaggt ggcctgtctg agttggataa   1860

agccggcttc atcaaaaggc agcttgttga gacacgccag atcaccaagc acgtggccca   1920

aattctcgat tcacgcatga acaccaagta cgatgaaaat gacaaactga ttcgagaggt   1980

gaaagttatt actctgaagt ctaagctggt ctcagatttc agaaaggact ttcagtttta   2040

taaggtgaga gagatcaaca attaccacca tgcgcatgat gcctacctga atgcagtggt   2100

aggcactgca cttatcaaaa aatatcccaa gcttgaatct gaatttgttt acggagacta   2160

taaagtgtac gatgttagga aaatgatcgc aaagtctgag caggaaatag gcaaggccac   2220

cgctaagtac ttcttttaca gcaatattat gaattttttc aagaccgaga ttacactggc   2280

caatggagag attcggaagc gaccacttat cgaaacaaac ggagaaacag gagaaatcgt   2340

gtgggacaag ggtagggatt tcgcgacagt ccggaaggtc ctgtccatgc cgcaggtgaa   2400

catcgttaaa aagaccgaag tacagaccgg aggcttctcc aaggaaagta tcctcccgaa   2460

aaggaacagc gacaagctga tcgcacgcaa aaaagattgg gaccccaaga aatacggcgg   2520

attcgattct cctacagtcg cttacagtgt actggttgtg gccaaagtgg agaaagggaa   2580

gtctaaaaaa ctcaaaagcg tcaaggaact gctgggcatc acaatcatgg agcgatcaag   2640

cttcgaaaaa aaccccatcg actttctcga ggcgaaagga tataaagagg tcaaaaaaga   2700

cctcatcatt aagcttccca agtactctct ctttgagctt gaaaacggcc ggaaacgaat   2760

gctcgctagt gcgggcgagc tgcagaaagg taacgagctg gcactgccct ctaaatacgt   2820

taatttcttg tatctggcca gccactatga aaagctcaaa gggtctcccg aagataatga   2880

gcagaagcag ctgttcgtgg aacaacacaa acactacctt gatgagatca tcgagcaaat   2940

aagcgaattc tccaaaagag tgatcctcgc cgacgctaac ctcgataagg tgctttctgc   3000

ttacaataag cacagggata agcccatcag ggagcaggca gaaaacatta tccacttgtt   3060

tactctgacc aacttgggcg cgcctgcagc cttcaagtac ttcgacacca ccatagacag   3120

aaagcggtac acctctacaa aggaggtcct ggacgccaca ctgattcatc agtcaattac   3180

ggggctctat gaaacaagaa tcgacctctc tcagctcggt ggagacagca gggctgaccc   3240

caagaagaag aggaaggtgt ctcgagctcg atgagtttgg acaaaccaca actagaatgc   3300

agtgaaaaaa atgctttatt tgtgaaattt gtgatgctat tgctttattt gtaaccatta   3360

taagctgcaa taaacaagtt aacaacaaca attgcattca ttttatgttt caggttcagg   3420

gggaggtgtg ggaggttttt taaagcaagt aaaacctcta caaatgtggt atctagagac   3480

attgattatt gactagttat taatagtaat caattacggg gtcattagtt catagcccat   3540

atatggagtt ccgcgttaca taacttacgg taaatggccc gcctggctga ccgcccaacg   3600

acccccgccc attgacgtca ataatgacgt atgttcccat agtaacgcca atagggactt   3660

tccattgacg tcaatgggtg gagtatttac ggtaaactgc ccacttggca gtacatcaag   3720

tgtatcatat gccaagtacg ccccctattg acgtcaatga cggtaaatgg cccgcctggc   3780

attatgccca gtacatgacc ttatgggact ttcctacttg gcagtacatc tacgtattag   3840

tcatcgctat taccatggtg atgcggtttt ggcagtacat caatgggcgt ggatagcggt   3900

ttgactcacg gggatttcca agtctccacc ccattgacgt caatgggagt ttgttttggc   3960

accaaaatca acgggacttt ccaaaatgtc gtaacaactc cgccccattg acgcaaatgg   4020

gcggtaggcg tgtacggtgg gaggtctata taagcagagc tctctggcta actagagaac   4080

ccactgctta ctggcttatc gaaattaata cgactcacta tagggagacc caagctggct   4140

agcatgaaca ttaacgacct gattcgggaa ataaagaaca aggactacac ggtcaagctg   4200

tcaggcaccg actccaactc tataacacag ctcattataa gggttaataa tgatggcaac   4260

gaatatgtca tctctgaatc cgagaatgaa tcaatcgtgg agaaattcat cagtgcattt   4320

aaaaacggct ggaaccagga gtacgaagat gaggaagagt tctacaatga tatgcaaact   4380

atcacactga aatctgagct gaactagctc gagcggccgc cactgtgctg gatatctgca   4440

gaattacaaa caccattgtc acactccatt atatacaaac accattgtca cactccatag   4500

cttaagttta aaccgctgat cagcctcgac tgtgccttct agttgccagc catctgttgt   4560

ttgcccctcc cccgtgcctt ccttgaccct ggaaggtgcc actcccactg tcctttccta   4620

ataaaatgag gaaattgcat cgcattgtct gagtaggtgt cattctattc tggggggtgg   4680

ggtggggcag gacagcaagg gggaggattg ggaagacaat agcaggcatg ctggggatgc   4740

ggtgggctct atggacgcgt gcggccgcag gtagataagt agcatggcgg gttaatcatt   4800

aactacaagg aacccctagt gatggagttg gccactccct ctctgcgcgc tcgctcgctc   4860

actgaggccg ggcgaccaaa ggtcgcccga cgcccgggct ttgcccgggc ggcctcagtg   4920

agcgagcgag cgcgcagcct aattaaggcc ttaattaaat ctggcgtaat catggtcata   4980

gctgtttcct gtgtgaaatt gttatccgct cacaattcca cacaacatac gagccggaag   5040

cataaagtgt aaagcctggg gtgcctaatg agtgagctaa ctcacattaa ttgcgttgcg   5100

ctcactgccc gctttccagt cgggaaacct gtcgtgccag ctgcattaat gaatcggcca   5160

acgcgcgggg agaggcggtt tgcgtattgg gcgctcttcc gcttcctcgc tcactgactc   5220

gctgcgctcg gtcgttcggc tgcggcgagc ggtatcagct cactcaaagg cggtaatacg   5280

gttatccaca gaatcagggg ataacgcagg aaagaacatg tgagcaaaac cgcagcaaaa   5340

ggccaggaac cgtaaaaagg ccgcgttgct ggcgtttttc cataggctcc gcccccctga   5400

cgagcatcac aaaaatcgac gctcaagtca gaggtggcga aacccgacag gactataaag   5460

ataccaggcg tttccccctg gaagctccct cgtgcgctct cctgttccga ccctgccgct   5520

taccggatac ctgtccgcct ttctcccttc gggaagcgtg gcgctttctc atagctcacg   5580

ctgtaggtat ctcagttcgg tgtaggtcgt tcgctccaag ctgggctgtg tgcacgaacc   5640

ccccgttcag cccgaccgct gcgccttatc cggtaactat cgtcttgagt ccaacccggt   5700

aagacacgac ttatcgccac tggcagcagc cactggtaac aggattagca gagcgaggta   5760

tgtaggcggt gctacagagt tcttgaagtg gtggcctaac tacggctaca ctagaaggac   5820

agtatttggt atctgcgctc tgctgaagcc agttaccttc ggaaaaagag ttggtagctc   5880

ttgatccggc aaacaaacca ccgctggtag cggtggtttt tttgtttgca agcagcagat   5940

tacgcgcaga aaaaaaggat ctcaagaaga tcctttgatc ttttctacgg ggtctgacgc   6000

tcagtggaac gaaaactcac gttaagggat tttggtcatg agattatcaa aaaggatctt   6060

cacctagatc cttttaaatt aaaaatgaag ttttaaatca atctaaagta tatatgagta   6120

aacttggtct gacagttacc aatgcttaat cagtgaggca cctatctcag cgatctgtct   6180

atttcgttca tccatagttg cctgactccc cgtcgtgtag ataactacga tacgggaggg   6240

cttaccatct ggccccagtg ctgcaatgat accgcgagac ccacgctcac cggctccaga   6300

tttatcagca ataaaccagc cagccggaag ggccgagcgc agaagtggtc ctgcaacttt   6360

atccgcctcc atccagtcta ttaattgttg ccgggaagct agagtaagta gttcgccagt   6420

taatagtttg cgcaacgttg ttaccattac tacaggcatc gtggtgtcac gctcgtcgtt   6480

tggtatggct tcattcagct ccggttccca acgatcaagg cgagttacat gatcccccat   6540

gttgtgcaaa aaagcggtta gctccttcgg tcctccgatc gttgtcagaa gtaagttggc   6600

cgcagtgtta tcactcatgg ttatggcagc actgcataat tctcttactg tcatgccatc   6660

cgtaagatgc ttttctgtga ctggtgagta ctcaaccaag tcattctgag aatagtgtat   6720

gcggcgaccg agttgctctt gcccggcgtc aatacgggat aataccgcgc cacatagcag   6780

aactttaaaa gtgctcatca ttggaaaacg ttcttcgggg cgaaaactct caaggatctt   6840

accactattg agatccagtt cgatgtaacc cactcgtgca cccaactgat cttcagcatc   6900

ttttactttc accagcgttt ctgggtgagc aaaaacagga aggcaaaatg ccgcaaaaaa   6960

gggaataagg gcgacacgga aatgttgaat actcatactc ttcctttttc aatattattg   7020

aagcatttat cagggttatt gtctcatgag cggatacata tttgaatgta tttagaaaaa   7080

taaacaaata ggggttccgc gcacatttcc ccgaaagatg ccacctgaaa ttataaacgt   7140

taatattttg ttaaaattcg cgttaaattt ttgttaaatc agctcatttt ttaaccaata   7200

ggccgaaatc ggcaaaatcc cttataaatc aaaagaatag accgagatag ggttgagtgt   7260

tgttccagtt tggaacaaga gtccactatt aaagaacgtg gactccaacg tcaaagggcg   7320

aaaaaccgtc tatcagggcg atggcccact acgtgaacca tcaccctaat caagtttttt   7380

ggggtcgagg tgccgtaaag cactaaatcg gaaccctaaa gggagccccc gatttagagc   7440

ttgacgggga aagccggcga acgtggcgag aaaggaaggg aagaaagcga aaggagcggg   7500

cgctagggcg ctggcaagtg tagcggtcac gctgcgcgta accaccacac ccgccgcgct   7560

taatgcgccg ctacagggcg cgtcccattc gccattcagg ctgcgcaact gttgggaagg   7620

gcgatcggtg cgggcctctt cgctattacg ccagctggcg aaagggggat gtgctgcaag   7680

gcgattaagt tgggtaacgc cagggttttc ccagtcacga cgttgtaaaa cgacggccag   7740

tgaattaggt taattaaggc tgcgcgctcg ctcgctcact gaggccgccc gggcaaagcc   7800

cgggcgtcgg gcgacctttg gtcgcccggc ctcagtgagc gagcgagcgc gcagagaggg   7860

agtggccaac tccatcacta ggggttcctt gtagttaatg attaacccgc catgctactt   7920

atctacctgc                                                          7930


<210>  16
<211>  7506
<212>  DNA
<213>  Artificial

<220>
<223>  C-Cas9-Intein_EFS-AcrIIA4-scaffold-BGH (AAV construct)

<400>  16
ggccgccatt atggaatgtg tgtcagttag ggtgtggaaa gtccccaggc tccccagcag     60

gcagaagtat gcaaagcatg catctcaatt agtcagcaac cagtcccggt ctcctcccat    120

gcatgtcaat attggccatt agccatatta ttcattggtt atatagcata aatcaatatt    180

ggctattggc cattgcatac gttgtatcta tatcataata tgtacattta tattggctca    240

tgtccaatat gaccgccatg ttggcattga ttattgacta gttattaata gtaatcaatt    300

acggggtcat tagttcatag cccatatatg gagttccgcg ttacataact tacggtaaat    360

ggcccgcctg gctgaccgcc caacgacccc cgcccattga cgtcaataat gacgtatgtt    420

cccatagtaa cgccaatagg gactttccat tgacgtcaat gggtggagta tttacggtaa    480

actgcccact tggcagtaca tcaagtgtat catatgccaa gtccgccccc tattgacgtc    540

aatgacggta aatggcccgc ctggcattat gcccagtaca tgaccttacg ggactttcct    600

acttggcagt acatctacgt attagtcatc gctattacca tggtgatgcg gttttggcag    660

tacaccaatg ggcgtggata gcggtttgac tcacggggat ttccaagtct ccaccccatt    720

gacgtcaatg ggagtttgtt ttggcaccaa aatcaacggg actttccaaa atgtcgtaat    780

aaccccgccc cgttgacgca aatgggcggt aggcgtgtac ggtgggaggt ctatataagc    840

agaggtcgtt tagtgaaccg tcagatcact agtagcttta ttgcggtagt ttatcacagt    900

taaattgcta acgcagtcag tgctcgactg atcacaggta agtatcaagg ttacaagaca    960

ggtttaagga ggccaataga aactgggctt gtcgagacag agaagattct tgcgtttctg   1020

ataggcacct attggtctta ctgacatcca ctttgccttt ctctccacag gggtaccgaa   1080

gccgctagcg ctaccggtcg ccaccatggc ggcggcgtgc ccggaactgc gtcagctggc   1140

gcagagcgat gtgtattggg atccgattgt gagcattgaa ccggatggcg tggaagaagt   1200

gtttgatctg accgtgccgg gcccgcataa ctttgtggcg aacgatatta ttgcgcataa   1260

ctctggccag ggggacagtc ttcacgagca catcgctaat cttgcaggta gcccagctat   1320

caaaaaggga atactgcaga ccgttaaggt cgtggatgaa ctcgtcaaag taatgggaag   1380

gcataagccc gagaatatcg ttatcgagat ggcccgagag aaccaaacta cccagaaggg   1440

acagaagaac agtagggaaa ggatgaagag gattgaagag ggtataaaag aactggggtc   1500

ccaaatcctt aaggaacacc cagttgaaaa cacccagctt cagaatgaga agctctacct   1560

gtactacctg cagaacggca gggacatgta cgtggatcag gaactggaca tcaatcggct   1620

ctccgactac gacgtggatc atatcgtgcc ccagtctttt ctcaaagatg attctattga   1680

taataaagtg ttgacaagat ccgataaaaa tagagggaag agtgataacg tcccctcaga   1740

agaagttgtc aagaaaatga aaaattattg gcggcagctg ctgaacgcca aactgatcac   1800

acaacggaag ttcgataatc tgactaaggc tgaacgaggt ggcctgtctg agttggataa   1860

agccggcttc atcaaaaggc agcttgttga gacacgccag atcaccaagc acgtggccca   1920

aattctcgat tcacgcatga acaccaagta cgatgaaaat gacaaactga ttcgagaggt   1980

gaaagttatt actctgaagt ctaagctggt ctcagatttc agaaaggact ttcagtttta   2040

taaggtgaga gagatcaaca attaccacca tgcgcatgat gcctacctga atgcagtggt   2100

aggcactgca cttatcaaaa aatatcccaa gcttgaatct gaatttgttt acggagacta   2160

taaagtgtac gatgttagga aaatgatcgc aaagtctgag caggaaatag gcaaggccac   2220

cgctaagtac ttcttttaca gcaatattat gaattttttc aagaccgaga ttacactggc   2280

caatggagag attcggaagc gaccacttat cgaaacaaac ggagaaacag gagaaatcgt   2340

gtgggacaag ggtagggatt tcgcgacagt ccggaaggtc ctgtccatgc cgcaggtgaa   2400

catcgttaaa aagaccgaag tacagaccgg aggcttctcc aaggaaagta tcctcccgaa   2460

aaggaacagc gacaagctga tcgcacgcaa aaaagattgg gaccccaaga aatacggcgg   2520

attcgattct cctacagtcg cttacagtgt actggttgtg gccaaagtgg agaaagggaa   2580

gtctaaaaaa ctcaaaagcg tcaaggaact gctgggcatc acaatcatgg agcgatcaag   2640

cttcgaaaaa aaccccatcg actttctcga ggcgaaagga tataaagagg tcaaaaaaga   2700

cctcatcatt aagcttccca agtactctct ctttgagctt gaaaacggcc ggaaacgaat   2760

gctcgctagt gcgggcgagc tgcagaaagg taacgagctg gcactgccct ctaaatacgt   2820

taatttcttg tatctggcca gccactatga aaagctcaaa gggtctcccg aagataatga   2880

gcagaagcag ctgttcgtgg aacaacacaa acactacctt gatgagatca tcgagcaaat   2940

aagcgaattc tccaaaagag tgatcctcgc cgacgctaac ctcgataagg tgctttctgc   3000

ttacaataag cacagggata agcccatcag ggagcaggca gaaaacatta tccacttgtt   3060

tactctgacc aacttgggcg cgcctgcagc cttcaagtac ttcgacacca ccatagacag   3120

aaagcggtac acctctacaa aggaggtcct ggacgccaca ctgattcatc agtcaattac   3180

ggggctctat gaaacaagaa tcgacctctc tcagctcggt ggagacagca gggctgaccc   3240

caagaagaag aggaaggtgt ctcgagctcg atgagtttgg acaaaccaca actagaatgc   3300

agtgaaaaaa atgctttatt tgtgaaattt gtgatgctat tgctttattt gtaaccatta   3360

taagctgcaa taaacaagtt aacaacaaca attgcattca ttttatgttt caggttcagg   3420

gggaggtgtg ggaggttttt taaagcaagt aaaacctcta caaatgtggt atctagagct   3480

ccggtgcccg tcagtgggca gagcgcacat cgcccacagt ccccgagaag ttggggggag   3540

gggtcggcaa ttgatccggt gcctagagaa ggtggcgcgg ggtaaactgg gaaagtgatg   3600

tcgtgtactg gctccgcctt tttcccgagg gtgggggaga accgtatata agtgcagtag   3660

tcgccgtgaa cgttcttttt cgcaacgggt ttgccgccag aacacaggga tccgccacca   3720

tgaacattaa cgacctgatt cgggaaataa agaacaagga ctacacggtc aagctgtcag   3780

gcaccgactc caactctata acacagctca ttataagggt taataatgat ggcaacgaat   3840

atgtcatctc tgaatccgag aatgaatcaa tcgtggagaa attcatcagt gcatttaaaa   3900

acggctggaa ccaggagtac gaagatgagg aagagttcta caatgatatg caaactatca   3960

cactgaaatc tgagctgaac tagctcgagc ggccgccact gtgctggata tctgcagaat   4020

tagagacgcc gttgatgttg aagtttatat accgttgatg ttgaagtcgt ctctagctta   4080

agtttaaacc gctgatcagc ctcgactgtg ccttctagtt gccagccatc tgttgtttgc   4140

ccctcccccg tgccttcctt gaccctggaa ggtgccactc ccactgtcct ttcctaataa   4200

aatgaggaaa ttgcatcgca ttgtctgagt aggtgtcatt ctattctggg gggtggggtg   4260

gggcaggaca gcaaggggga ggattgggaa gacaatagca ggcatgctgg ggatgcggtg   4320

ggctctatgg acgcgtgcgg ccgcaggtag ataagtagca tggcgggtta atcattaact   4380

acaaggaacc cctagtgatg gagttggcca ctccctctct gcgcgctcgc tcgctcactg   4440

aggccgggcg accaaaggtc gcccgacgcc cgggctttgc ccgggcggcc tcagtgagcg   4500

agcgagcgcg cagcctaatt aaggccttaa ttaaatctgg cgtaatcatg gtcatagctg   4560

tttcctgtgt gaaattgtta tccgctcaca attccacaca acatacgagc cggaagcata   4620

aagtgtaaag cctggggtgc ctaatgagtg agctaactca cattaattgc gttgcgctca   4680

ctgcccgctt tccagtcggg aaacctgtcg tgccagctgc attaatgaat cggccaacgc   4740

gcggggagag gcggtttgcg tattgggcgc tcttccgctt cctcgctcac tgactcgctg   4800

cgctcggtcg ttcggctgcg gcgagcggta tcagctcact caaaggcggt aatacggtta   4860

tccacagaat caggggataa cgcaggaaag aacatgtgag caaaaccgca gcaaaaggcc   4920

aggaaccgta aaaaggccgc gttgctggcg tttttccata ggctccgccc ccctgacgag   4980

catcacaaaa atcgacgctc aagtcagagg tggcgaaacc cgacaggact ataaagatac   5040

caggcgtttc cccctggaag ctccctcgtg cgctctcctg ttccgaccct gccgcttacc   5100

ggatacctgt ccgcctttct cccttcggga agcgtggcgc tttctcatag ctcacgctgt   5160

aggtatctca gttcggtgta ggtcgttcgc tccaagctgg gctgtgtgca cgaacccccc   5220

gttcagcccg accgctgcgc cttatccggt aactatcgtc ttgagtccaa cccggtaaga   5280

cacgacttat cgccactggc agcagccact ggtaacagga ttagcagagc gaggtatgta   5340

ggcggtgcta cagagttctt gaagtggtgg cctaactacg gctacactag aaggacagta   5400

tttggtatct gcgctctgct gaagccagtt accttcggaa aaagagttgg tagctcttga   5460

tccggcaaac aaaccaccgc tggtagcggt ggtttttttg tttgcaagca gcagattacg   5520

cgcagaaaaa aaggatctca agaagatcct ttgatctttt ctacggggtc tgacgctcag   5580

tggaacgaaa actcacgtta agggattttg gtcatgagat tatcaaaaag gatcttcacc   5640

tagatccttt taaattaaaa atgaagtttt aaatcaatct aaagtatata tgagtaaact   5700

tggtctgaca gttaccaatg cttaatcagt gaggcaccta tctcagcgat ctgtctattt   5760

cgttcatcca tagttgcctg actccccgtc gtgtagataa ctacgatacg ggagggctta   5820

ccatctggcc ccagtgctgc aatgataccg cgagacccac gctcaccggc tccagattta   5880

tcagcaataa accagccagc cggaagggcc gagcgcagaa gtggtcctgc aactttatcc   5940

gcctccatcc agtctattaa ttgttgccgg gaagctagag taagtagttc gccagttaat   6000

agtttgcgca acgttgttac cattactaca ggcatcgtgg tgtcacgctc gtcgtttggt   6060

atggcttcat tcagctccgg ttcccaacga tcaaggcgag ttacatgatc ccccatgttg   6120

tgcaaaaaag cggttagctc cttcggtcct ccgatcgttg tcagaagtaa gttggccgca   6180

gtgttatcac tcatggttat ggcagcactg cataattctc ttactgtcat gccatccgta   6240

agatgctttt ctgtgactgg tgagtactca accaagtcat tctgagaata gtgtatgcgg   6300

cgaccgagtt gctcttgccc ggcgtcaata cgggataata ccgcgccaca tagcagaact   6360

ttaaaagtgc tcatcattgg aaaacgttct tcggggcgaa aactctcaag gatcttacca   6420

ctattgagat ccagttcgat gtaacccact cgtgcaccca actgatcttc agcatctttt   6480

actttcacca gcgtttctgg gtgagcaaaa acaggaaggc aaaatgccgc aaaaaaggga   6540

ataagggcga cacggaaatg ttgaatactc atactcttcc tttttcaata ttattgaagc   6600

atttatcagg gttattgtct catgagcgga tacatatttg aatgtattta gaaaaataaa   6660

caaatagggg ttccgcgcac atttccccga aagatgccac ctgaaattat aaacgttaat   6720

attttgttaa aattcgcgtt aaatttttgt taaatcagct cattttttaa ccaataggcc   6780

gaaatcggca aaatccctta taaatcaaaa gaatagaccg agatagggtt gagtgttgtt   6840

ccagtttgga acaagagtcc actattaaag aacgtggact ccaacgtcaa agggcgaaaa   6900

accgtctatc agggcgatgg cccactacgt gaaccatcac cctaatcaag ttttttgggg   6960

tcgaggtgcc gtaaagcact aaatcggaac cctaaaggga gcccccgatt tagagcttga   7020

cggggaaagc cggcgaacgt ggcgagaaag gaagggaaga aagcgaaagg agcgggcgct   7080

agggcgctgg caagtgtagc ggtcacgctg cgcgtaacca ccacacccgc cgcgcttaat   7140

gcgccgctac agggcgcgtc ccattcgcca ttcaggctgc gcaactgttg ggaagggcga   7200

tcggtgcggg cctcttcgct attacgccag ctggcgaaag ggggatgtgc tgcaaggcga   7260

ttaagttggg taacgccagg gttttcccag tcacgacgtt gtaaaacgac ggccagtgaa   7320

ttaggttaat taaggctgcg cgctcgctcg ctcactgagg ccgcccgggc aaagcccggg   7380

cgtcgggcga cctttggtcg cccggcctca gtgagcgagc gagcgcgcag agagggagtg   7440

gccaactcca tcactagggg ttccttgtag ttaatgatta acccgccatg ctacttatct   7500

acctgc                                                              7506


<210>  17
<211>  7506
<212>  DNA
<213>  Artificial

<220>
<223>   C-Cas9-Intein_EFS-AcrIIA4-2xmir122BS-BGH (AAV construct)

<400>  17
ggccgccatt atggaatgtg tgtcagttag ggtgtggaaa gtccccaggc tccccagcag     60

gcagaagtat gcaaagcatg catctcaatt agtcagcaac cagtcccggt ctcctcccat    120

gcatgtcaat attggccatt agccatatta ttcattggtt atatagcata aatcaatatt    180

ggctattggc cattgcatac gttgtatcta tatcataata tgtacattta tattggctca    240

tgtccaatat gaccgccatg ttggcattga ttattgacta gttattaata gtaatcaatt    300

acggggtcat tagttcatag cccatatatg gagttccgcg ttacataact tacggtaaat    360

ggcccgcctg gctgaccgcc caacgacccc cgcccattga cgtcaataat gacgtatgtt    420

cccatagtaa cgccaatagg gactttccat tgacgtcaat gggtggagta tttacggtaa    480

actgcccact tggcagtaca tcaagtgtat catatgccaa gtccgccccc tattgacgtc    540

aatgacggta aatggcccgc ctggcattat gcccagtaca tgaccttacg ggactttcct    600

acttggcagt acatctacgt attagtcatc gctattacca tggtgatgcg gttttggcag    660

tacaccaatg ggcgtggata gcggtttgac tcacggggat ttccaagtct ccaccccatt    720

gacgtcaatg ggagtttgtt ttggcaccaa aatcaacggg actttccaaa atgtcgtaat    780

aaccccgccc cgttgacgca aatgggcggt aggcgtgtac ggtgggaggt ctatataagc    840

agaggtcgtt tagtgaaccg tcagatcact agtagcttta ttgcggtagt ttatcacagt    900

taaattgcta acgcagtcag tgctcgactg atcacaggta agtatcaagg ttacaagaca    960

ggtttaagga ggccaataga aactgggctt gtcgagacag agaagattct tgcgtttctg   1020

ataggcacct attggtctta ctgacatcca ctttgccttt ctctccacag gggtaccgaa   1080

gccgctagcg ctaccggtcg ccaccatggc ggcggcgtgc ccggaactgc gtcagctggc   1140

gcagagcgat gtgtattggg atccgattgt gagcattgaa ccggatggcg tggaagaagt   1200

gtttgatctg accgtgccgg gcccgcataa ctttgtggcg aacgatatta ttgcgcataa   1260

ctctggccag ggggacagtc ttcacgagca catcgctaat cttgcaggta gcccagctat   1320

caaaaaggga atactgcaga ccgttaaggt cgtggatgaa ctcgtcaaag taatgggaag   1380

gcataagccc gagaatatcg ttatcgagat ggcccgagag aaccaaacta cccagaaggg   1440

acagaagaac agtagggaaa ggatgaagag gattgaagag ggtataaaag aactggggtc   1500

ccaaatcctt aaggaacacc cagttgaaaa cacccagctt cagaatgaga agctctacct   1560

gtactacctg cagaacggca gggacatgta cgtggatcag gaactggaca tcaatcggct   1620

ctccgactac gacgtggatc atatcgtgcc ccagtctttt ctcaaagatg attctattga   1680

taataaagtg ttgacaagat ccgataaaaa tagagggaag agtgataacg tcccctcaga   1740

agaagttgtc aagaaaatga aaaattattg gcggcagctg ctgaacgcca aactgatcac   1800

acaacggaag ttcgataatc tgactaaggc tgaacgaggt ggcctgtctg agttggataa   1860

agccggcttc atcaaaaggc agcttgttga gacacgccag atcaccaagc acgtggccca   1920

aattctcgat tcacgcatga acaccaagta cgatgaaaat gacaaactga ttcgagaggt   1980

gaaagttatt actctgaagt ctaagctggt ctcagatttc agaaaggact ttcagtttta   2040

taaggtgaga gagatcaaca attaccacca tgcgcatgat gcctacctga atgcagtggt   2100

aggcactgca cttatcaaaa aatatcccaa gcttgaatct gaatttgttt acggagacta   2160

taaagtgtac gatgttagga aaatgatcgc aaagtctgag caggaaatag gcaaggccac   2220

cgctaagtac ttcttttaca gcaatattat gaattttttc aagaccgaga ttacactggc   2280

caatggagag attcggaagc gaccacttat cgaaacaaac ggagaaacag gagaaatcgt   2340

gtgggacaag ggtagggatt tcgcgacagt ccggaaggtc ctgtccatgc cgcaggtgaa   2400

catcgttaaa aagaccgaag tacagaccgg aggcttctcc aaggaaagta tcctcccgaa   2460

aaggaacagc gacaagctga tcgcacgcaa aaaagattgg gaccccaaga aatacggcgg   2520

attcgattct cctacagtcg cttacagtgt actggttgtg gccaaagtgg agaaagggaa   2580

gtctaaaaaa ctcaaaagcg tcaaggaact gctgggcatc acaatcatgg agcgatcaag   2640

cttcgaaaaa aaccccatcg actttctcga ggcgaaagga tataaagagg tcaaaaaaga   2700

cctcatcatt aagcttccca agtactctct ctttgagctt gaaaacggcc ggaaacgaat   2760

gctcgctagt gcgggcgagc tgcagaaagg taacgagctg gcactgccct ctaaatacgt   2820

taatttcttg tatctggcca gccactatga aaagctcaaa gggtctcccg aagataatga   2880

gcagaagcag ctgttcgtgg aacaacacaa acactacctt gatgagatca tcgagcaaat   2940

aagcgaattc tccaaaagag tgatcctcgc cgacgctaac ctcgataagg tgctttctgc   3000

ttacaataag cacagggata agcccatcag ggagcaggca gaaaacatta tccacttgtt   3060

tactctgacc aacttgggcg cgcctgcagc cttcaagtac ttcgacacca ccatagacag   3120

aaagcggtac acctctacaa aggaggtcct ggacgccaca ctgattcatc agtcaattac   3180

ggggctctat gaaacaagaa tcgacctctc tcagctcggt ggagacagca gggctgaccc   3240

caagaagaag aggaaggtgt ctcgagctcg atgagtttgg acaaaccaca actagaatgc   3300

agtgaaaaaa atgctttatt tgtgaaattt gtgatgctat tgctttattt gtaaccatta   3360

taagctgcaa taaacaagtt aacaacaaca attgcattca ttttatgttt caggttcagg   3420

gggaggtgtg ggaggttttt taaagcaagt aaaacctcta caaatgtggt atctagagct   3480

ccggtgcccg tcagtgggca gagcgcacat cgcccacagt ccccgagaag ttggggggag   3540

gggtcggcaa ttgatccggt gcctagagaa ggtggcgcgg ggtaaactgg gaaagtgatg   3600

tcgtgtactg gctccgcctt tttcccgagg gtgggggaga accgtatata agtgcagtag   3660

tcgccgtgaa cgttcttttt cgcaacgggt ttgccgccag aacacaggga tccgccacca   3720

tgaacattaa cgacctgatt cgggaaataa agaacaagga ctacacggtc aagctgtcag   3780

gcaccgactc caactctata acacagctca ttataagggt taataatgat ggcaacgaat   3840

atgtcatctc tgaatccgag aatgaatcaa tcgtggagaa attcatcagt gcatttaaaa   3900

acggctggaa ccaggagtac gaagatgagg aagagttcta caatgatatg caaactatca   3960

cactgaaatc tgagctgaac tagctcgagc ggccgccact gtgctggata tctgcagaat   4020

tacaaacacc attgtcacac tccattatat acaaacacca ttgtcacact ccatagctta   4080

agtttaaacc gctgatcagc ctcgactgtg ccttctagtt gccagccatc tgttgtttgc   4140

ccctcccccg tgccttcctt gaccctggaa ggtgccactc ccactgtcct ttcctaataa   4200

aatgaggaaa ttgcatcgca ttgtctgagt aggtgtcatt ctattctggg gggtggggtg   4260

gggcaggaca gcaaggggga ggattgggaa gacaatagca ggcatgctgg ggatgcggtg   4320

ggctctatgg acgcgtgcgg ccgcaggtag ataagtagca tggcgggtta atcattaact   4380

acaaggaacc cctagtgatg gagttggcca ctccctctct gcgcgctcgc tcgctcactg   4440

aggccgggcg accaaaggtc gcccgacgcc cgggctttgc ccgggcggcc tcagtgagcg   4500

agcgagcgcg cagcctaatt aaggccttaa ttaaatctgg cgtaatcatg gtcatagctg   4560

tttcctgtgt gaaattgtta tccgctcaca attccacaca acatacgagc cggaagcata   4620

aagtgtaaag cctggggtgc ctaatgagtg agctaactca cattaattgc gttgcgctca   4680

ctgcccgctt tccagtcggg aaacctgtcg tgccagctgc attaatgaat cggccaacgc   4740

gcggggagag gcggtttgcg tattgggcgc tcttccgctt cctcgctcac tgactcgctg   4800

cgctcggtcg ttcggctgcg gcgagcggta tcagctcact caaaggcggt aatacggtta   4860

tccacagaat caggggataa cgcaggaaag aacatgtgag caaaaccgca gcaaaaggcc   4920

aggaaccgta aaaaggccgc gttgctggcg tttttccata ggctccgccc ccctgacgag   4980

catcacaaaa atcgacgctc aagtcagagg tggcgaaacc cgacaggact ataaagatac   5040

caggcgtttc cccctggaag ctccctcgtg cgctctcctg ttccgaccct gccgcttacc   5100

ggatacctgt ccgcctttct cccttcggga agcgtggcgc tttctcatag ctcacgctgt   5160

aggtatctca gttcggtgta ggtcgttcgc tccaagctgg gctgtgtgca cgaacccccc   5220

gttcagcccg accgctgcgc cttatccggt aactatcgtc ttgagtccaa cccggtaaga   5280

cacgacttat cgccactggc agcagccact ggtaacagga ttagcagagc gaggtatgta   5340

ggcggtgcta cagagttctt gaagtggtgg cctaactacg gctacactag aaggacagta   5400

tttggtatct gcgctctgct gaagccagtt accttcggaa aaagagttgg tagctcttga   5460

tccggcaaac aaaccaccgc tggtagcggt ggtttttttg tttgcaagca gcagattacg   5520

cgcagaaaaa aaggatctca agaagatcct ttgatctttt ctacggggtc tgacgctcag   5580

tggaacgaaa actcacgtta agggattttg gtcatgagat tatcaaaaag gatcttcacc   5640

tagatccttt taaattaaaa atgaagtttt aaatcaatct aaagtatata tgagtaaact   5700

tggtctgaca gttaccaatg cttaatcagt gaggcaccta tctcagcgat ctgtctattt   5760

cgttcatcca tagttgcctg actccccgtc gtgtagataa ctacgatacg ggagggctta   5820

ccatctggcc ccagtgctgc aatgataccg cgagacccac gctcaccggc tccagattta   5880

tcagcaataa accagccagc cggaagggcc gagcgcagaa gtggtcctgc aactttatcc   5940

gcctccatcc agtctattaa ttgttgccgg gaagctagag taagtagttc gccagttaat   6000

agtttgcgca acgttgttac cattactaca ggcatcgtgg tgtcacgctc gtcgtttggt   6060

atggcttcat tcagctccgg ttcccaacga tcaaggcgag ttacatgatc ccccatgttg   6120

tgcaaaaaag cggttagctc cttcggtcct ccgatcgttg tcagaagtaa gttggccgca   6180

gtgttatcac tcatggttat ggcagcactg cataattctc ttactgtcat gccatccgta   6240

agatgctttt ctgtgactgg tgagtactca accaagtcat tctgagaata gtgtatgcgg   6300

cgaccgagtt gctcttgccc ggcgtcaata cgggataata ccgcgccaca tagcagaact   6360

ttaaaagtgc tcatcattgg aaaacgttct tcggggcgaa aactctcaag gatcttacca   6420

ctattgagat ccagttcgat gtaacccact cgtgcaccca actgatcttc agcatctttt   6480

actttcacca gcgtttctgg gtgagcaaaa acaggaaggc aaaatgccgc aaaaaaggga   6540

ataagggcga cacggaaatg ttgaatactc atactcttcc tttttcaata ttattgaagc   6600

atttatcagg gttattgtct catgagcgga tacatatttg aatgtattta gaaaaataaa   6660

caaatagggg ttccgcgcac atttccccga aagatgccac ctgaaattat aaacgttaat   6720

attttgttaa aattcgcgtt aaatttttgt taaatcagct cattttttaa ccaataggcc   6780

gaaatcggca aaatccctta taaatcaaaa gaatagaccg agatagggtt gagtgttgtt   6840

ccagtttgga acaagagtcc actattaaag aacgtggact ccaacgtcaa agggcgaaaa   6900

accgtctatc agggcgatgg cccactacgt gaaccatcac cctaatcaag ttttttgggg   6960

tcgaggtgcc gtaaagcact aaatcggaac cctaaaggga gcccccgatt tagagcttga   7020

cggggaaagc cggcgaacgt ggcgagaaag gaagggaaga aagcgaaagg agcgggcgct   7080

agggcgctgg caagtgtagc ggtcacgctg cgcgtaacca ccacacccgc cgcgcttaat   7140

gcgccgctac agggcgcgtc ccattcgcca ttcaggctgc gcaactgttg ggaagggcga   7200

tcggtgcggg cctcttcgct attacgccag ctggcgaaag ggggatgtgc tgcaaggcga   7260

ttaagttggg taacgccagg gttttcccag tcacgacgtt gtaaaacgac ggccagtgaa   7320

ttaggttaat taaggctgcg cgctcgctcg ctcactgagg ccgcccgggc aaagcccggg   7380

cgtcgggcga cctttggtcg cccggcctca gtgagcgagc gagcgcgcag agagggagtg   7440

gccaactcca tcactagggg ttccttgtag ttaatgatta acccgccatg ctacttatct   7500

acctgc                                                              7506


<210>  18
<211>  7409
<212>  DNA
<213>  Artificial

<220>
<223>  C-Cas9-Intein_EFS-FLAG-NLS-AcrIIA4-2xmir122BS-miniPolyA (AAV  
       construct)

<400>  18
ggccgccatt atggaatgtg tgtcagttag ggtgtggaaa gtccccaggc tccccagcag     60

gcagaagtat gcaaagcatg catctcaatt agtcagcaac cagtcccggt ctcctcccat    120

gcatgtcaat attggccatt agccatatta ttcattggtt atatagcata aatcaatatt    180

ggctattggc cattgcatac gttgtatcta tatcataata tgtacattta tattggctca    240

tgtccaatat gaccgccatg ttggcattga ttattgacta gttattaata gtaatcaatt    300

acggggtcat tagttcatag cccatatatg gagttccgcg ttacataact tacggtaaat    360

ggcccgcctg gctgaccgcc caacgacccc cgcccattga cgtcaataat gacgtatgtt    420

cccatagtaa cgccaatagg gactttccat tgacgtcaat gggtggagta tttacggtaa    480

actgcccact tggcagtaca tcaagtgtat catatgccaa gtccgccccc tattgacgtc    540

aatgacggta aatggcccgc ctggcattat gcccagtaca tgaccttacg ggactttcct    600

acttggcagt acatctacgt attagtcatc gctattacca tggtgatgcg gttttggcag    660

tacaccaatg ggcgtggata gcggtttgac tcacggggat ttccaagtct ccaccccatt    720

gacgtcaatg ggagtttgtt ttggcaccaa aatcaacggg actttccaaa atgtcgtaat    780

aaccccgccc cgttgacgca aatgggcggt aggcgtgtac ggtgggaggt ctatataagc    840

agaggtcgtt tagtgaaccg tcagatcact agtagcttta ttgcggtagt ttatcacagt    900

taaattgcta acgcagtcag tgctcgactg atcacaggta agtatcaagg ttacaagaca    960

ggtttaagga ggccaataga aactgggctt gtcgagacag agaagattct tgcgtttctg   1020

ataggcacct attggtctta ctgacatcca ctttgccttt ctctccacag gggtaccgaa   1080

gccgctagcg ctaccggtcg ccaccatggc ggcggcgtgc ccggaactgc gtcagctggc   1140

gcagagcgat gtgtattggg atccgattgt gagcattgaa ccggatggcg tggaagaagt   1200

gtttgatctg accgtgccgg gcccgcataa ctttgtggcg aacgatatta ttgcgcataa   1260

ctctggccag ggggacagtc ttcacgagca catcgctaat cttgcaggta gcccagctat   1320

caaaaaggga atactgcaga ccgttaaggt cgtggatgaa ctcgtcaaag taatgggaag   1380

gcataagccc gagaatatcg ttatcgagat ggcccgagag aaccaaacta cccagaaggg   1440

acagaagaac agtagggaaa ggatgaagag gattgaagag ggtataaaag aactggggtc   1500

ccaaatcctt aaggaacacc cagttgaaaa cacccagctt cagaatgaga agctctacct   1560

gtactacctg cagaacggca gggacatgta cgtggatcag gaactggaca tcaatcggct   1620

ctccgactac gacgtggatc atatcgtgcc ccagtctttt ctcaaagatg attctattga   1680

taataaagtg ttgacaagat ccgataaaaa tagagggaag agtgataacg tcccctcaga   1740

agaagttgtc aagaaaatga aaaattattg gcggcagctg ctgaacgcca aactgatcac   1800

acaacggaag ttcgataatc tgactaaggc tgaacgaggt ggcctgtctg agttggataa   1860

agccggcttc atcaaaaggc agcttgttga gacacgccag atcaccaagc acgtggccca   1920

aattctcgat tcacgcatga acaccaagta cgatgaaaat gacaaactga ttcgagaggt   1980

gaaagttatt actctgaagt ctaagctggt ctcagatttc agaaaggact ttcagtttta   2040

taaggtgaga gagatcaaca attaccacca tgcgcatgat gcctacctga atgcagtggt   2100

aggcactgca cttatcaaaa aatatcccaa gcttgaatct gaatttgttt acggagacta   2160

taaagtgtac gatgttagga aaatgatcgc aaagtctgag caggaaatag gcaaggccac   2220

cgctaagtac ttcttttaca gcaatattat gaattttttc aagaccgaga ttacactggc   2280

caatggagag attcggaagc gaccacttat cgaaacaaac ggagaaacag gagaaatcgt   2340

gtgggacaag ggtagggatt tcgcgacagt ccggaaggtc ctgtccatgc cgcaggtgaa   2400

catcgttaaa aagaccgaag tacagaccgg aggcttctcc aaggaaagta tcctcccgaa   2460

aaggaacagc gacaagctga tcgcacgcaa aaaagattgg gaccccaaga aatacggcgg   2520

attcgattct cctacagtcg cttacagtgt actggttgtg gccaaagtgg agaaagggaa   2580

gtctaaaaaa ctcaaaagcg tcaaggaact gctgggcatc acaatcatgg agcgatcaag   2640

cttcgaaaaa aaccccatcg actttctcga ggcgaaagga tataaagagg tcaaaaaaga   2700

cctcatcatt aagcttccca agtactctct ctttgagctt gaaaacggcc ggaaacgaat   2760

gctcgctagt gcgggcgagc tgcagaaagg taacgagctg gcactgccct ctaaatacgt   2820

taatttcttg tatctggcca gccactatga aaagctcaaa gggtctcccg aagataatga   2880

gcagaagcag ctgttcgtgg aacaacacaa acactacctt gatgagatca tcgagcaaat   2940

aagcgaattc tccaaaagag tgatcctcgc cgacgctaac ctcgataagg tgctttctgc   3000

ttacaataag cacagggata agcccatcag ggagcaggca gaaaacatta tccacttgtt   3060

tactctgacc aacttgggcg cgcctgcagc cttcaagtac ttcgacacca ccatagacag   3120

aaagcggtac acctctacaa aggaggtcct ggacgccaca ctgattcatc agtcaattac   3180

ggggctctat gaaacaagaa tcgacctctc tcagctcggt ggagacagca gggctgaccc   3240

caagaagaag aggaaggtgt ctcgagctcg atgagtttgg acaaaccaca actagaatgc   3300

agtgaaaaaa atgctttatt tgtgaaattt gtgatgctat tgctttattt gtaaccatta   3360

taagctgcaa taaacaagtt aacaacaaca attgcattca ttttatgttt caggttcagg   3420

gggaggtgtg ggaggttttt taaagcaagt aaaacctcta caaatgtggt atctagagct   3480

ccggtgcccg tcagtgggca gagcgcacat cgcccacagt ccccgagaag ttggggggag   3540

gggtcggcaa ttgatccggt gcctagagaa ggtggcgcgg ggtaaactgg gaaagtgatg   3600

tcgtgtactg gctccgcctt tttcccgagg gtgggggaga accgtatata agtgcagtag   3660

tcgccgtgaa cgttcttttt cgcaacgggt ttgccgccag aacacaggga tccgccacca   3720

tggactataa ggacgatgac gataaaccca agaagaagcg aaaagtcgga ggttccatga   3780

acattaacga cctgattcgg gaaataaaga acaaggacta cacggtcaag ctgtcaggca   3840

ccgactccaa ctctataaca cagctcatta taagggttaa taatgatggc aacgaatatg   3900

tcatctctga atccgagaat gaatcaatcg tggagaaatt catcagtgca tttaaaaacg   3960

gctggaacca ggagtacgaa gatgaggaag agttctacaa tgatatgcaa actatcacac   4020

tgaaatctga gctgaactag ctcgagcggc cgccactgtg ctggatatct gcagaattca   4080

aacaccattg tcacactcca ttatatcaaa caccattgtc acactccatt aattagagac   4140

gagctcgtct ctagcttaag tttaaaccgc tgatcagcct cgagctagca ataaaggatc   4200

gtttattttc attggaagcg tgtgttggtt tttacgcgtg cggccgcagg tagataagta   4260

gcatggcggg ttaatcatta actacaagga acccctagtg atggagttgg ccactccctc   4320

tctgcgcgct cgctcgctca ctgaggccgg gcgaccaaag gtcgcccgac gcccgggctt   4380

tgcccgggcg gcctcagtga gcgagcgagc gcgcagccta attaaggcct taattaaatc   4440

tggcgtaatc atggtcatag ctgtttcctg tgtgaaattg ttatccgctc acaattccac   4500

acaacatacg agccggaagc ataaagtgta aagcctgggg tgcctaatga gtgagctaac   4560

tcacattaat tgcgttgcgc tcactgcccg ctttccagtc gggaaacctg tcgtgccagc   4620

tgcattaatg aatcggccaa cgcgcgggga gaggcggttt gcgtattggg cgctcttccg   4680

cttcctcgct cactgactcg ctgcgctcgg tcgttcggct gcggcgagcg gtatcagctc   4740

actcaaaggc ggtaatacgg ttatccacag aatcagggga taacgcagga aagaacatgt   4800

gagcaaaacc gcagcaaaag gccaggaacc gtaaaaaggc cgcgttgctg gcgtttttcc   4860

ataggctccg cccccctgac gagcatcaca aaaatcgacg ctcaagtcag aggtggcgaa   4920

acccgacagg actataaaga taccaggcgt ttccccctgg aagctccctc gtgcgctctc   4980

ctgttccgac cctgccgctt accggatacc tgtccgcctt tctcccttcg ggaagcgtgg   5040

cgctttctca tagctcacgc tgtaggtatc tcagttcggt gtaggtcgtt cgctccaagc   5100

tgggctgtgt gcacgaaccc cccgttcagc ccgaccgctg cgccttatcc ggtaactatc   5160

gtcttgagtc caacccggta agacacgact tatcgccact ggcagcagcc actggtaaca   5220

ggattagcag agcgaggtat gtaggcggtg ctacagagtt cttgaagtgg tggcctaact   5280

acggctacac tagaaggaca gtatttggta tctgcgctct gctgaagcca gttaccttcg   5340

gaaaaagagt tggtagctct tgatccggca aacaaaccac cgctggtagc ggtggttttt   5400

ttgtttgcaa gcagcagatt acgcgcagaa aaaaaggatc tcaagaagat cctttgatct   5460

tttctacggg gtctgacgct cagtggaacg aaaactcacg ttaagggatt ttggtcatga   5520

gattatcaaa aaggatcttc acctagatcc ttttaaatta aaaatgaagt tttaaatcaa   5580

tctaaagtat atatgagtaa acttggtctg acagttacca atgcttaatc agtgaggcac   5640

ctatctcagc gatctgtcta tttcgttcat ccatagttgc ctgactcccc gtcgtgtaga   5700

taactacgat acgggagggc ttaccatctg gccccagtgc tgcaatgata ccgcgagacc   5760

cacgctcacc ggctccagat ttatcagcaa taaaccagcc agccggaagg gccgagcgca   5820

gaagtggtcc tgcaacttta tccgcctcca tccagtctat taattgttgc cgggaagcta   5880

gagtaagtag ttcgccagtt aatagtttgc gcaacgttgt taccattact acaggcatcg   5940

tggtgtcacg ctcgtcgttt ggtatggctt cattcagctc cggttcccaa cgatcaaggc   6000

gagttacatg atcccccatg ttgtgcaaaa aagcggttag ctccttcggt cctccgatcg   6060

ttgtcagaag taagttggcc gcagtgttat cactcatggt tatggcagca ctgcataatt   6120

ctcttactgt catgccatcc gtaagatgct tttctgtgac tggtgagtac tcaaccaagt   6180

cattctgaga atagtgtatg cggcgaccga gttgctcttg cccggcgtca atacgggata   6240

ataccgcgcc acatagcaga actttaaaag tgctcatcat tggaaaacgt tcttcggggc   6300

gaaaactctc aaggatctta ccactattga gatccagttc gatgtaaccc actcgtgcac   6360

ccaactgatc ttcagcatct tttactttca ccagcgtttc tgggtgagca aaaacaggaa   6420

ggcaaaatgc cgcaaaaaag ggaataaggg cgacacggaa atgttgaata ctcatactct   6480

tcctttttca atattattga agcatttatc agggttattg tctcatgagc ggatacatat   6540

ttgaatgtat ttagaaaaat aaacaaatag gggttccgcg cacatttccc cgaaagatgc   6600

cacctgaaat tataaacgtt aatattttgt taaaattcgc gttaaatttt tgttaaatca   6660

gctcattttt taaccaatag gccgaaatcg gcaaaatccc ttataaatca aaagaataga   6720

ccgagatagg gttgagtgtt gttccagttt ggaacaagag tccactatta aagaacgtgg   6780

actccaacgt caaagggcga aaaaccgtct atcagggcga tggcccacta cgtgaaccat   6840

caccctaatc aagttttttg gggtcgaggt gccgtaaagc actaaatcgg aaccctaaag   6900

ggagcccccg atttagagct tgacggggaa agccggcgaa cgtggcgaga aaggaaggga   6960

agaaagcgaa aggagcgggc gctagggcgc tggcaagtgt agcggtcacg ctgcgcgtaa   7020

ccaccacacc cgccgcgctt aatgcgccgc tacagggcgc gtcccattcg ccattcaggc   7080

tgcgcaactg ttgggaaggg cgatcggtgc gggcctcttc gctattacgc cagctggcga   7140

aagggggatg tgctgcaagg cgattaagtt gggtaacgcc agggttttcc cagtcacgac   7200

gttgtaaaac gacggccagt gaattaggtt aattaaggct gcgcgctcgc tcgctcactg   7260

aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg tcgcccggcc tcagtgagcg   7320

agcgagcgcg cagagaggga gtggccaact ccatcactag gggttccttg tagttaatga   7380

ttaacccgcc atgctactta tctacctgc                                     7409


<210>  19
<211>  7388
<212>  DNA
<213>  Artificial

<220>
<223>  C-Cas9-Intein_EFS-FLAG-NLS-AcrIIA4-scaffold-miniPolyA (AAV 
       construct)

<400>  19
ggccgccatt atggaatgtg tgtcagttag ggtgtggaaa gtccccaggc tccccagcag     60

gcagaagtat gcaaagcatg catctcaatt agtcagcaac cagtcccggt ctcctcccat    120

gcatgtcaat attggccatt agccatatta ttcattggtt atatagcata aatcaatatt    180

ggctattggc cattgcatac gttgtatcta tatcataata tgtacattta tattggctca    240

tgtccaatat gaccgccatg ttggcattga ttattgacta gttattaata gtaatcaatt    300

acggggtcat tagttcatag cccatatatg gagttccgcg ttacataact tacggtaaat    360

ggcccgcctg gctgaccgcc caacgacccc cgcccattga cgtcaataat gacgtatgtt    420

cccatagtaa cgccaatagg gactttccat tgacgtcaat gggtggagta tttacggtaa    480

actgcccact tggcagtaca tcaagtgtat catatgccaa gtccgccccc tattgacgtc    540

aatgacggta aatggcccgc ctggcattat gcccagtaca tgaccttacg ggactttcct    600

acttggcagt acatctacgt attagtcatc gctattacca tggtgatgcg gttttggcag    660

tacaccaatg ggcgtggata gcggtttgac tcacggggat ttccaagtct ccaccccatt    720

gacgtcaatg ggagtttgtt ttggcaccaa aatcaacggg actttccaaa atgtcgtaat    780

aaccccgccc cgttgacgca aatgggcggt aggcgtgtac ggtgggaggt ctatataagc    840

agaggtcgtt tagtgaaccg tcagatcact agtagcttta ttgcggtagt ttatcacagt    900

taaattgcta acgcagtcag tgctcgactg atcacaggta agtatcaagg ttacaagaca    960

ggtttaagga ggccaataga aactgggctt gtcgagacag agaagattct tgcgtttctg   1020

ataggcacct attggtctta ctgacatcca ctttgccttt ctctccacag gggtaccgaa   1080

gccgctagcg ctaccggtcg ccaccatggc ggcggcgtgc ccggaactgc gtcagctggc   1140

gcagagcgat gtgtattggg atccgattgt gagcattgaa ccggatggcg tggaagaagt   1200

gtttgatctg accgtgccgg gcccgcataa ctttgtggcg aacgatatta ttgcgcataa   1260

ctctggccag ggggacagtc ttcacgagca catcgctaat cttgcaggta gcccagctat   1320

caaaaaggga atactgcaga ccgttaaggt cgtggatgaa ctcgtcaaag taatgggaag   1380

gcataagccc gagaatatcg ttatcgagat ggcccgagag aaccaaacta cccagaaggg   1440

acagaagaac agtagggaaa ggatgaagag gattgaagag ggtataaaag aactggggtc   1500

ccaaatcctt aaggaacacc cagttgaaaa cacccagctt cagaatgaga agctctacct   1560

gtactacctg cagaacggca gggacatgta cgtggatcag gaactggaca tcaatcggct   1620

ctccgactac gacgtggatc atatcgtgcc ccagtctttt ctcaaagatg attctattga   1680

taataaagtg ttgacaagat ccgataaaaa tagagggaag agtgataacg tcccctcaga   1740

agaagttgtc aagaaaatga aaaattattg gcggcagctg ctgaacgcca aactgatcac   1800

acaacggaag ttcgataatc tgactaaggc tgaacgaggt ggcctgtctg agttggataa   1860

agccggcttc atcaaaaggc agcttgttga gacacgccag atcaccaagc acgtggccca   1920

aattctcgat tcacgcatga acaccaagta cgatgaaaat gacaaactga ttcgagaggt   1980

gaaagttatt actctgaagt ctaagctggt ctcagatttc agaaaggact ttcagtttta   2040

taaggtgaga gagatcaaca attaccacca tgcgcatgat gcctacctga atgcagtggt   2100

aggcactgca cttatcaaaa aatatcccaa gcttgaatct gaatttgttt acggagacta   2160

taaagtgtac gatgttagga aaatgatcgc aaagtctgag caggaaatag gcaaggccac   2220

cgctaagtac ttcttttaca gcaatattat gaattttttc aagaccgaga ttacactggc   2280

caatggagag attcggaagc gaccacttat cgaaacaaac ggagaaacag gagaaatcgt   2340

gtgggacaag ggtagggatt tcgcgacagt ccggaaggtc ctgtccatgc cgcaggtgaa   2400

catcgttaaa aagaccgaag tacagaccgg aggcttctcc aaggaaagta tcctcccgaa   2460

aaggaacagc gacaagctga tcgcacgcaa aaaagattgg gaccccaaga aatacggcgg   2520

attcgattct cctacagtcg cttacagtgt actggttgtg gccaaagtgg agaaagggaa   2580

gtctaaaaaa ctcaaaagcg tcaaggaact gctgggcatc acaatcatgg agcgatcaag   2640

cttcgaaaaa aaccccatcg actttctcga ggcgaaagga tataaagagg tcaaaaaaga   2700

cctcatcatt aagcttccca agtactctct ctttgagctt gaaaacggcc ggaaacgaat   2760

gctcgctagt gcgggcgagc tgcagaaagg taacgagctg gcactgccct ctaaatacgt   2820

taatttcttg tatctggcca gccactatga aaagctcaaa gggtctcccg aagataatga   2880

gcagaagcag ctgttcgtgg aacaacacaa acactacctt gatgagatca tcgagcaaat   2940

aagcgaattc tccaaaagag tgatcctcgc cgacgctaac ctcgataagg tgctttctgc   3000

ttacaataag cacagggata agcccatcag ggagcaggca gaaaacatta tccacttgtt   3060

tactctgacc aacttgggcg cgcctgcagc cttcaagtac ttcgacacca ccatagacag   3120

aaagcggtac acctctacaa aggaggtcct ggacgccaca ctgattcatc agtcaattac   3180

ggggctctat gaaacaagaa tcgacctctc tcagctcggt ggagacagca gggctgaccc   3240

caagaagaag aggaaggtgt ctcgagctcg atgagtttgg acaaaccaca actagaatgc   3300

agtgaaaaaa atgctttatt tgtgaaattt gtgatgctat tgctttattt gtaaccatta   3360

taagctgcaa taaacaagtt aacaacaaca attgcattca ttttatgttt caggttcagg   3420

gggaggtgtg ggaggttttt taaagcaagt aaaacctcta caaatgtggt atctagagct   3480

ccggtgcccg tcagtgggca gagcgcacat cgcccacagt ccccgagaag ttggggggag   3540

gggtcggcaa ttgatccggt gcctagagaa ggtggcgcgg ggtaaactgg gaaagtgatg   3600

tcgtgtactg gctccgcctt tttcccgagg gtgggggaga accgtatata agtgcagtag   3660

tcgccgtgaa cgttcttttt cgcaacgggt ttgccgccag aacacaggga tccgccacca   3720

tggactataa ggacgatgac gataaaccca agaagaagcg aaaagtcgga ggttccatga   3780

acattaacga cctgattcgg gaaataaaga acaaggacta cacggtcaag ctgtcaggca   3840

ccgactccaa ctctataaca cagctcatta taagggttaa taatgatggc aacgaatatg   3900

tcatctctga atccgagaat gaatcaatcg tggagaaatt catcagtgca tttaaaaacg   3960

gctggaacca ggagtacgaa gatgaggaag agttctacaa tgatatgcaa actatcacac   4020

tgaaatctga gctgaactag ctcgagcggc cgccactgtg ctggatatct gcagaattag   4080

agacgccgtt gatgttgaag tttatatacc gttgatgttg aagtcgtctc tagcttaagt   4140

ttaaaccgct gatcagcctc gagctagcaa taaaggatcg tttattttca ttggaagcgt   4200

gtgttggttt ttacgcgtgc ggccgcaggt agataagtag catggcgggt taatcattaa   4260

ctacaaggaa cccctagtga tggagttggc cactccctct ctgcgcgctc gctcgctcac   4320

tgaggccggg cgaccaaagg tcgcccgacg cccgggcttt gcccgggcgg cctcagtgag   4380

cgagcgagcg cgcagcctaa ttaaggcctt aattaaatct ggcgtaatca tggtcatagc   4440

tgtttcctgt gtgaaattgt tatccgctca caattccaca caacatacga gccggaagca   4500

taaagtgtaa agcctggggt gcctaatgag tgagctaact cacattaatt gcgttgcgct   4560

cactgcccgc tttccagtcg ggaaacctgt cgtgccagct gcattaatga atcggccaac   4620

gcgcggggag aggcggtttg cgtattgggc gctcttccgc ttcctcgctc actgactcgc   4680

tgcgctcggt cgttcggctg cggcgagcgg tatcagctca ctcaaaggcg gtaatacggt   4740

tatccacaga atcaggggat aacgcaggaa agaacatgtg agcaaaaccg cagcaaaagg   4800

ccaggaaccg taaaaaggcc gcgttgctgg cgtttttcca taggctccgc ccccctgacg   4860

agcatcacaa aaatcgacgc tcaagtcaga ggtggcgaaa cccgacagga ctataaagat   4920

accaggcgtt tccccctgga agctccctcg tgcgctctcc tgttccgacc ctgccgctta   4980

ccggatacct gtccgccttt ctcccttcgg gaagcgtggc gctttctcat agctcacgct   5040

gtaggtatct cagttcggtg taggtcgttc gctccaagct gggctgtgtg cacgaacccc   5100

ccgttcagcc cgaccgctgc gccttatccg gtaactatcg tcttgagtcc aacccggtaa   5160

gacacgactt atcgccactg gcagcagcca ctggtaacag gattagcaga gcgaggtatg   5220

taggcggtgc tacagagttc ttgaagtggt ggcctaacta cggctacact agaaggacag   5280

tatttggtat ctgcgctctg ctgaagccag ttaccttcgg aaaaagagtt ggtagctctt   5340

gatccggcaa acaaaccacc gctggtagcg gtggtttttt tgtttgcaag cagcagatta   5400

cgcgcagaaa aaaaggatct caagaagatc ctttgatctt ttctacgggg tctgacgctc   5460

agtggaacga aaactcacgt taagggattt tggtcatgag attatcaaaa aggatcttca   5520

cctagatcct tttaaattaa aaatgaagtt ttaaatcaat ctaaagtata tatgagtaaa   5580

cttggtctga cagttaccaa tgcttaatca gtgaggcacc tatctcagcg atctgtctat   5640

ttcgttcatc catagttgcc tgactccccg tcgtgtagat aactacgata cgggagggct   5700

taccatctgg ccccagtgct gcaatgatac cgcgagaccc acgctcaccg gctccagatt   5760

tatcagcaat aaaccagcca gccggaaggg ccgagcgcag aagtggtcct gcaactttat   5820

ccgcctccat ccagtctatt aattgttgcc gggaagctag agtaagtagt tcgccagtta   5880

atagtttgcg caacgttgtt accattacta caggcatcgt ggtgtcacgc tcgtcgtttg   5940

gtatggcttc attcagctcc ggttcccaac gatcaaggcg agttacatga tcccccatgt   6000

tgtgcaaaaa agcggttagc tccttcggtc ctccgatcgt tgtcagaagt aagttggccg   6060

cagtgttatc actcatggtt atggcagcac tgcataattc tcttactgtc atgccatccg   6120

taagatgctt ttctgtgact ggtgagtact caaccaagtc attctgagaa tagtgtatgc   6180

ggcgaccgag ttgctcttgc ccggcgtcaa tacgggataa taccgcgcca catagcagaa   6240

ctttaaaagt gctcatcatt ggaaaacgtt cttcggggcg aaaactctca aggatcttac   6300

cactattgag atccagttcg atgtaaccca ctcgtgcacc caactgatct tcagcatctt   6360

ttactttcac cagcgtttct gggtgagcaa aaacaggaag gcaaaatgcc gcaaaaaagg   6420

gaataagggc gacacggaaa tgttgaatac tcatactctt cctttttcaa tattattgaa   6480

gcatttatca gggttattgt ctcatgagcg gatacatatt tgaatgtatt tagaaaaata   6540

aacaaatagg ggttccgcgc acatttcccc gaaagatgcc acctgaaatt ataaacgtta   6600

atattttgtt aaaattcgcg ttaaattttt gttaaatcag ctcatttttt aaccaatagg   6660

ccgaaatcgg caaaatccct tataaatcaa aagaatagac cgagataggg ttgagtgttg   6720

ttccagtttg gaacaagagt ccactattaa agaacgtgga ctccaacgtc aaagggcgaa   6780

aaaccgtcta tcagggcgat ggcccactac gtgaaccatc accctaatca agttttttgg   6840

ggtcgaggtg ccgtaaagca ctaaatcgga accctaaagg gagcccccga tttagagctt   6900

gacggggaaa gccggcgaac gtggcgagaa aggaagggaa gaaagcgaaa ggagcgggcg   6960

ctagggcgct ggcaagtgta gcggtcacgc tgcgcgtaac caccacaccc gccgcgctta   7020

atgcgccgct acagggcgcg tcccattcgc cattcaggct gcgcaactgt tgggaagggc   7080

gatcggtgcg ggcctcttcg ctattacgcc agctggcgaa agggggatgt gctgcaaggc   7140

gattaagttg ggtaacgcca gggttttccc agtcacgacg ttgtaaaacg acggccagtg   7200

aattaggtta attaaggctg cgcgctcgct cgctcactga ggccgcccgg gcaaagcccg   7260

ggcgtcgggc gacctttggt cgcccggcct cagtgagcga gcgagcgcgc agagagggag   7320

tggccaactc catcactagg ggttccttgt agttaatgat taacccgcca tgctacttat   7380

ctacctgc                                                            7388


<210>  20
<211>  87
<212>  PRT
<213>  Listeria monocytogenes

<400>  20

Met Asn Ile Asn Asp Leu Ile Arg Glu Ile Lys Asn Lys Asp Tyr Thr 
1               5                   10                  15      


Val Lys Leu Ser Gly Thr Asp Ser Asn Ser Ile Thr Gln Leu Ile Ile 
            20                  25                  30          


Arg Val Asn Asn Asp Gly Asn Glu Tyr Val Ile Ser Glu Ser Glu Asn 
        35                  40                  45              


Glu Ser Ile Val Glu Lys Phe Ile Ser Ala Phe Lys Asn Gly Trp Asn 
    50                  55                  60                  


Gln Glu Tyr Glu Asp Glu Glu Glu Phe Tyr Asn Asp Met Gln Thr Ile 
65                  70                  75                  80  


Thr Leu Lys Ser Glu Leu Asn 
                85          


<210>  21
<211>  261
<212>  DNA
<213>  Listeria monocytogenes

<400>  21
atgaacatta acgacctgat tcgggaaata aagaacaagg actacacggt caagctgtca     60

ggcaccgact ccaactctat aacacagctc attataaggg ttaataatga tggcaacgaa    120

tatgtcatct ctgaatccga gaatgaatca atcgtggaga aattcatcag tgcatttaaa    180

aacggctgga accaggagta cgaagatgag gaagagttct acaatgatat gcaaactatc    240

acactgaaat ctgagctgaa c                                              261


<210>  22
<211>  712
<212>  PRT
<213>  Artificial

<220>
<223>  Cas9 S. pyogenes N-terminal fragment (N-Cas9)

<400>  22

Asp Lys Lys Tyr Ser Ile Gly Leu Asp Ile Gly Thr Asn Ser Val Gly 
1               5                   10                  15      


Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe Lys 
            20                  25                  30          


Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile Gly 
        35                  40                  45              


Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu Lys 
    50                  55                  60                  


Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys Tyr 
65                  70                  75                  80  


Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser Phe 
                85                  90                  95      


Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys His 
            100                 105                 110         


Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr His 
        115                 120                 125             


Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp Ser 
    130                 135                 140                 


Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His Met 
145                 150                 155                 160 


Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro Asp 
                165                 170                 175     


Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr Asn 
            180                 185                 190         


Gln Leu Phe Glu Glu Asn Pro Ile Asn Ala Ser Gly Val Asp Ala Lys 
        195                 200                 205             


Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn Leu 
    210                 215                 220                 


Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn Leu 
225                 230                 235                 240 


Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe Asp 
                245                 250                 255     


Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp Asp 
            260                 265                 270         


Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp Leu 
        275                 280                 285             


Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp Ile 
    290                 295                 300                 


Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser Met 
305                 310                 315                 320 


Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys Ala 
                325                 330                 335     


Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe Asp 
            340                 345                 350         


Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser Gln 
        355                 360                 365             


Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp Gly 
    370                 375                 380                 


Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg Lys 
385                 390                 395                 400 


Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu Gly 
                405                 410                 415     


Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe Leu 
            420                 425                 430         


Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile Pro 
        435                 440                 445             


Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp Met 
    450                 455                 460                 


Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu Val 
465                 470                 475                 480 


Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr Asn 
                485                 490                 495     


Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser Leu 
            500                 505                 510         


Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys Tyr 
        515                 520                 525             


Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln Lys 
    530                 535                 540                 


Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr Val 
545                 550                 555                 560 


Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp Ser 
                565                 570                 575     


Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly Thr 
            580                 585                 590         


Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp Asn 
        595                 600                 605             


Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr Leu 
    610                 615                 620                 


Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala His 
625                 630                 635                 640 


Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr Thr 
                645                 650                 655     


Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp Lys 
            660                 665                 670         


Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe Ala 
        675                 680                 685             


Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe Lys 
    690                 695                 700                 


Glu Asp Ile Gln Lys Ala Gln Val 
705                 710         


<210>  23
<211>  2136
<212>  DNA
<213>  Artificial

<220>
<223>  N-Cas9 encoding sequence

<400>  23
gacaagaagt actccattgg gctcgatatc ggcacaaaca gcgtcggctg ggccgtcatt     60

acggacgagt acaaggtgcc gagcaaaaaa ttcaaagttc tgggcaatac cgatcgccac    120

agcataaaga agaacctcat tggcgccctc ctgttcgact ccggggaaac ggccgaagcc    180

acgcggctca aaagaacagc acggcgcaga tatacccgca gaaagaatcg gatctgctac    240

ctgcaggaga tctttagtaa tgagatggct aaggtggatg actctttctt ccataggctg    300

gaggagtcct ttttggtgga ggaggataaa aagcacgagc gccacccaat ctttggcaat    360

atcgtggacg aggtggcgta ccatgaaaag tacccaacca tatatcatct gaggaagaag    420

cttgtagaca gtactgataa ggctgacttg cggttgatct atctcgcgct ggcgcatatg    480

atcaaatttc ggggacactt cctcatcgag ggggacctga acccagacaa cagcgatgtc    540

gacaaactct ttatccaact ggttcagact tacaatcagc ttttcgaaga gaacccgatc    600

aacgcatccg gagttgacgc caaagcaatc ctgagcgcta ggctgtccaa atcccggcgg    660

ctcgaaaacc tcatcgcaca gctccctggg gagaagaaga acggcctgtt tggtaatctt    720

atcgccctgt cactcgggct gacccccaac tttaaatcta acttcgacct ggccgaagat    780

gccaagcttc aactgagcaa agacacctac gatgatgatc tcgacaatct gctggcccag    840

atcggcgacc agtacgcaga cctttttttg gcggcaaaga acctgtcaga cgccattctg    900

ctgagtgata ttctgcgagt gaacacggag atcaccaaag ctccgctgag cgctagtatg    960

atcaagcgct atgatgagca ccaccaagac ttgactttgc tgaaggccct tgtcagacag   1020

caactgcctg agaagtacaa ggaaattttc ttcgatcagt ctaaaaatgg ctacgccgga   1080

tacattgacg gcggagcaag ccaggaggaa ttttacaaat ttattaagcc catcttggaa   1140

aaaatggacg gcaccgagga gctgctggta aagcttaaca gagaagatct gttgcgcaaa   1200

cagcgcactt tcgacaatgg aagcatcccc caccagattc acctgggcga actgcacgct   1260

atcctcaggc ggcaagagga tttctacccc tttttgaaag ataacaggga aaagattgag   1320

aaaatcctca catttcggat accctactat gtaggccccc tcgcccgggg aaattccaga   1380

ttcgcgtgga tgactcgcaa atcagaagag accatcactc cctggaactt cgaggaagtc   1440

gtggataagg gggcctctgc ccagtccttc atcgaaagga tgactaactt tgataaaaat   1500

ctgcctaacg aaaaggtgct tcctaaacac tctctgctgt acgagtactt cacagtttat   1560

aacgagctca ccaaggtcaa atacgtcaca gaagggatga gaaagccagc attcctgtct   1620

ggagagcaga agaaagctat cgtggacctc ctcttcaaga cgaaccggaa agttaccgtg   1680

aaacagctca aagaagacta tttcaaaaag attgaatgtt tcgactctgt tgaaatcagc   1740

ggagtggagg atcgcttcaa cgcatccctg ggaacgtatc acgatctcct gaaaatcatt   1800

aaagacaagg acttcctgga caatgaggag aacgaggaca ttcttgagga cattgtcctc   1860

acccttacgt tgtttgaaga tagggagatg attgaagaac gcttgaaaac ttacgctcat   1920

ctcttcgacg acaaagtcat gaaacagctc aagaggcgcc gatatacagg atgggggcgg   1980

ctgtcaagaa aactgatcaa tgggatccga gacaagcaga gtggaaagac aatcctggat   2040

tttcttaagt ccgatggatt tgccaaccgg aacttcatgc agttgatcca tgatgactct   2100

ctcaccttta aggaggacat ccagaaagca caagtt                             2136


<210>  24
<211>  102
<212>  PRT
<213>  Artificial

<220>
<223>  N-Intein

<400>  24

Cys Leu Ala Gly Asp Thr Leu Ile Thr Leu Ala Asp Gly Arg Arg Val 
1               5                   10                  15      


Pro Ile Arg Glu Leu Val Ser Gln Gln Asn Phe Ser Val Trp Ala Leu 
            20                  25                  30          


Asn Pro Gln Thr Tyr Arg Leu Glu Arg Ala Arg Val Ser Arg Ala Phe 
        35                  40                  45              


Cys Thr Gly Ile Lys Pro Val Tyr Arg Leu Thr Thr Arg Leu Gly Arg 
    50                  55                  60                  


Ser Ile Arg Ala Thr Ala Asn His Arg Phe Leu Thr Pro Gln Gly Trp 
65                  70                  75                  80  


Lys Arg Val Asp Glu Leu Gln Pro Gly Asp Tyr Leu Ala Leu Pro Arg 
                85                  90                  95      


Arg Ile Pro Thr Ala Ser 
            100         


<210>  25
<211>  306
<212>  DNA
<213>  Artificial

<220>
<223>  N-Intein encoding

<400>  25
tgtctggctg gcgatactct cattaccctg gccgatggac gacgagtgcc tattagagaa     60

ctggtgtcac agcagaattt ttccgtgtgg gctctgaatc ctcagactta ccgcctggag    120

agggctagag tgagtagagc tttctgtacc ggcatcaaac ctgtgtaccg cctcaccact    180

agactgggga gatccattag ggccactgcc aaccaccgat ttctcacacc tcagggctgg    240

aaacgagtcg atgaactcca gcctggagat tacctggctc tgcctaggag aatccctact    300

gcctcc                                                               306


<210>  26
<211>  7
<212>  PRT
<213>  Artificial

<220>
<223>  SV40-NLS

<400>  26

Pro Lys Lys Lys Arg Lys Val 
1               5           


<210>  27
<211>  21
<212>  DNA
<213>  Artificial

<220>
<223>  SV40-NLS encoding

<400>  27
ccaaagaaga agcggaaggt c                                               21


<210>  28
<211>  831
<212>  PRT
<213>  Artificial

<220>
<223>  SV40NLS-SpCas9 N-fragment-Intein

<400>  28

Met Ala Pro Lys Lys Lys Arg Lys Val Gly Ile His Gly Val Pro Ala 
1               5                   10                  15      


Ala Asp Lys Lys Tyr Ser Ile Gly Leu Asp Ile Gly Thr Asn Ser Val 
            20                  25                  30          


Gly Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe 
        35                  40                  45              


Lys Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile 
    50                  55                  60                  


Gly Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu 
65                  70                  75                  80  


Lys Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys 
                85                  90                  95      


Tyr Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser 
            100                 105                 110         


Phe Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys 
        115                 120                 125             


His Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr 
    130                 135                 140                 


His Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp 
145                 150                 155                 160 


Ser Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His 
                165                 170                 175     


Met Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro 
            180                 185                 190         


Asp Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr 
        195                 200                 205             


Asn Gln Leu Phe Glu Glu Asn Pro Ile Asn Ala Ser Gly Val Asp Ala 
    210                 215                 220                 


Lys Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn 
225                 230                 235                 240 


Leu Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn 
                245                 250                 255     


Leu Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe 
            260                 265                 270         


Asp Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp 
        275                 280                 285             


Asp Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp 
    290                 295                 300                 


Leu Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp 
305                 310                 315                 320 


Ile Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser 
                325                 330                 335     


Met Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys 
            340                 345                 350         


Ala Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe 
        355                 360                 365             


Asp Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser 
    370                 375                 380                 


Gln Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp 
385                 390                 395                 400 


Gly Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg 
                405                 410                 415     


Lys Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu 
            420                 425                 430         


Gly Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe 
        435                 440                 445             


Leu Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile 
    450                 455                 460                 


Pro Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp 
465                 470                 475                 480 


Met Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu 
                485                 490                 495     


Val Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr 
            500                 505                 510         


Asn Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser 
        515                 520                 525             


Leu Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys 
    530                 535                 540                 


Tyr Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln 
545                 550                 555                 560 


Lys Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr 
                565                 570                 575     


Val Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp 
            580                 585                 590         


Ser Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly 
        595                 600                 605             


Thr Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp 
    610                 615                 620                 


Asn Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr 
625                 630                 635                 640 


Leu Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala 
                645                 650                 655     


His Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr 
            660                 665                 670         


Thr Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp 
        675                 680                 685             


Lys Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe 
    690                 695                 700                 


Ala Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe 
705                 710                 715                 720 


Lys Glu Asp Ile Gln Lys Ala Gln Val Cys Leu Ala Gly Asp Thr Leu 
                725                 730                 735     


Ile Thr Leu Ala Asp Gly Arg Arg Val Pro Ile Arg Glu Leu Val Ser 
            740                 745                 750         


Gln Gln Asn Phe Ser Val Trp Ala Leu Asn Pro Gln Thr Tyr Arg Leu 
        755                 760                 765             


Glu Arg Ala Arg Val Ser Arg Ala Phe Cys Thr Gly Ile Lys Pro Val 
    770                 775                 780                 


Tyr Arg Leu Thr Thr Arg Leu Gly Arg Ser Ile Arg Ala Thr Ala Asn 
785                 790                 795                 800 


His Arg Phe Leu Thr Pro Gln Gly Trp Lys Arg Val Asp Glu Leu Gln 
                805                 810                 815     


Pro Gly Asp Tyr Leu Ala Leu Pro Arg Arg Ile Pro Thr Ala Ser 
            820                 825                 830     


<210>  29
<211>  2493
<212>  DNA
<213>  Artificial

<220>
<223>  SV40NLS-SpCas9 N-fragment-Intein encoding

<400>  29
atggccccaa agaagaagcg gaaggtcggt atccacggag tcccagcagc cgacaagaag     60

tactccattg ggctcgatat cggcacaaac agcgtcggct gggccgtcat tacggacgag    120

tacaaggtgc cgagcaaaaa attcaaagtt ctgggcaata ccgatcgcca cagcataaag    180

aagaacctca ttggcgccct cctgttcgac tccggggaaa cggccgaagc cacgcggctc    240

aaaagaacag cacggcgcag atatacccgc agaaagaatc ggatctgcta cctgcaggag    300

atctttagta atgagatggc taaggtggat gactctttct tccataggct ggaggagtcc    360

tttttggtgg aggaggataa aaagcacgag cgccacccaa tctttggcaa tatcgtggac    420

gaggtggcgt accatgaaaa gtacccaacc atatatcatc tgaggaagaa gcttgtagac    480

agtactgata aggctgactt gcggttgatc tatctcgcgc tggcgcatat gatcaaattt    540

cggggacact tcctcatcga gggggacctg aacccagaca acagcgatgt cgacaaactc    600

tttatccaac tggttcagac ttacaatcag cttttcgaag agaacccgat caacgcatcc    660

ggagttgacg ccaaagcaat cctgagcgct aggctgtcca aatcccggcg gctcgaaaac    720

ctcatcgcac agctccctgg ggagaagaag aacggcctgt ttggtaatct tatcgccctg    780

tcactcgggc tgacccccaa ctttaaatct aacttcgacc tggccgaaga tgccaagctt    840

caactgagca aagacaccta cgatgatgat ctcgacaatc tgctggccca gatcggcgac    900

cagtacgcag accttttttt ggcggcaaag aacctgtcag acgccattct gctgagtgat    960

attctgcgag tgaacacgga gatcaccaaa gctccgctga gcgctagtat gatcaagcgc   1020

tatgatgagc accaccaaga cttgactttg ctgaaggccc ttgtcagaca gcaactgcct   1080

gagaagtaca aggaaatttt cttcgatcag tctaaaaatg gctacgccgg atacattgac   1140

ggcggagcaa gccaggagga attttacaaa tttattaagc ccatcttgga aaaaatggac   1200

ggcaccgagg agctgctggt aaagcttaac agagaagatc tgttgcgcaa acagcgcact   1260

ttcgacaatg gaagcatccc ccaccagatt cacctgggcg aactgcacgc tatcctcagg   1320

cggcaagagg atttctaccc ctttttgaaa gataacaggg aaaagattga gaaaatcctc   1380

acatttcgga taccctacta tgtaggcccc ctcgcccggg gaaattccag attcgcgtgg   1440

atgactcgca aatcagaaga gaccatcact ccctggaact tcgaggaagt cgtggataag   1500

ggggcctctg cccagtcctt catcgaaagg atgactaact ttgataaaaa tctgcctaac   1560

gaaaaggtgc ttcctaaaca ctctctgctg tacgagtact tcacagttta taacgagctc   1620

accaaggtca aatacgtcac agaagggatg agaaagccag cattcctgtc tggagagcag   1680

aagaaagcta tcgtggacct cctcttcaag acgaaccgga aagttaccgt gaaacagctc   1740

aaagaagact atttcaaaaa gattgaatgt ttcgactctg ttgaaatcag cggagtggag   1800

gatcgcttca acgcatccct gggaacgtat cacgatctcc tgaaaatcat taaagacaag   1860

gacttcctgg acaatgagga gaacgaggac attcttgagg acattgtcct cacccttacg   1920

ttgtttgaag atagggagat gattgaagaa cgcttgaaaa cttacgctca tctcttcgac   1980

gacaaagtca tgaaacagct caagaggcgc cgatatacag gatgggggcg gctgtcaaga   2040

aaactgatca atgggatccg agacaagcag agtggaaaga caatcctgga ttttcttaag   2100

tccgatggat ttgccaaccg gaacttcatg cagttgatcc atgatgactc tctcaccttt   2160

aaggaggaca tccagaaagc acaagtttgt ctggctggcg atactctcat taccctggcc   2220

gatggacgac gagtgcctat tagagaactg gtgtcacagc agaatttttc cgtgtgggct   2280

ctgaatcctc agacttaccg cctggagagg gctagagtga gtagagcttt ctgtaccggc   2340

atcaaacctg tgtaccgcct caccactaga ctggggagat ccattagggc cactgccaac   2400

caccgatttc tcacacctca gggctggaaa cgagtcgatg aactccagcc tggagattac   2460

ctggctctgc ctaggagaat ccctactgcc tcc                                2493


<210>  30
<211>  655
<212>  PRT
<213>  Artificial

<220>
<223>  C-Cas9

<400>  30

Ser Gly Gln Gly Asp Ser Leu His Glu His Ile Ala Asn Leu Ala Gly 
1               5                   10                  15      


Ser Pro Ala Ile Lys Lys Gly Ile Leu Gln Thr Val Lys Val Val Asp 
            20                  25                  30          


Glu Leu Val Lys Val Met Gly Arg His Lys Pro Glu Asn Ile Val Ile 
        35                  40                  45              


Glu Met Ala Arg Glu Asn Gln Thr Thr Gln Lys Gly Gln Lys Asn Ser 
    50                  55                  60                  


Arg Glu Arg Met Lys Arg Ile Glu Glu Gly Ile Lys Glu Leu Gly Ser 
65                  70                  75                  80  


Gln Ile Leu Lys Glu His Pro Val Glu Asn Thr Gln Leu Gln Asn Glu 
                85                  90                  95      


Lys Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly Arg Asp Met Tyr Val Asp 
            100                 105                 110         


Gln Glu Leu Asp Ile Asn Arg Leu Ser Asp Tyr Asp Val Asp His Ile 
        115                 120                 125             


Val Pro Gln Ser Phe Leu Lys Asp Asp Ser Ile Asp Asn Lys Val Leu 
    130                 135                 140                 


Thr Arg Ser Asp Lys Asn Arg Gly Lys Ser Asp Asn Val Pro Ser Glu 
145                 150                 155                 160 


Glu Val Val Lys Lys Met Lys Asn Tyr Trp Arg Gln Leu Leu Asn Ala 
                165                 170                 175     


Lys Leu Ile Thr Gln Arg Lys Phe Asp Asn Leu Thr Lys Ala Glu Arg 
            180                 185                 190         


Gly Gly Leu Ser Glu Leu Asp Lys Ala Gly Phe Ile Lys Arg Gln Leu 
        195                 200                 205             


Val Glu Thr Arg Gln Ile Thr Lys His Val Ala Gln Ile Leu Asp Ser 
    210                 215                 220                 


Arg Met Asn Thr Lys Tyr Asp Glu Asn Asp Lys Leu Ile Arg Glu Val 
225                 230                 235                 240 


Lys Val Ile Thr Leu Lys Ser Lys Leu Val Ser Asp Phe Arg Lys Asp 
                245                 250                 255     


Phe Gln Phe Tyr Lys Val Arg Glu Ile Asn Asn Tyr His His Ala His 
            260                 265                 270         


Asp Ala Tyr Leu Asn Ala Val Val Gly Thr Ala Leu Ile Lys Lys Tyr 
        275                 280                 285             


Pro Lys Leu Glu Ser Glu Phe Val Tyr Gly Asp Tyr Lys Val Tyr Asp 
    290                 295                 300                 


Val Arg Lys Met Ile Ala Lys Ser Glu Gln Glu Ile Gly Lys Ala Thr 
305                 310                 315                 320 


Ala Lys Tyr Phe Phe Tyr Ser Asn Ile Met Asn Phe Phe Lys Thr Glu 
                325                 330                 335     


Ile Thr Leu Ala Asn Gly Glu Ile Arg Lys Arg Pro Leu Ile Glu Thr 
            340                 345                 350         


Asn Gly Glu Thr Gly Glu Ile Val Trp Asp Lys Gly Arg Asp Phe Ala 
        355                 360                 365             


Thr Val Arg Lys Val Leu Ser Met Pro Gln Val Asn Ile Val Lys Lys 
    370                 375                 380                 


Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser Ile Leu Pro Lys 
385                 390                 395                 400 


Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp Trp Asp Pro Lys 
                405                 410                 415     


Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr Ser Val Leu Val 
            420                 425                 430         


Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu Lys Ser Val Lys 
        435                 440                 445             


Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser Phe Glu Lys Asn 
    450                 455                 460                 


Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu Val Lys Lys Asp 
465                 470                 475                 480 


Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu Leu Glu Asn Gly 
                485                 490                 495     


Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln Lys Gly Asn Glu 
            500                 505                 510         


Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr Leu Ala Ser His 
        515                 520                 525             


Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu Gln Lys Gln Leu 
    530                 535                 540                 


Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile Ile Glu Gln Ile 
545                 550                 555                 560 


Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala Asn Leu Asp Lys 
                565                 570                 575     


Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro Ile Arg Glu Gln 
            580                 585                 590         


Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn Leu Gly Ala Pro 
        595                 600                 605             


Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg Lys Arg Tyr Thr 
    610                 615                 620                 


Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His Gln Ser Ile Thr 
625                 630                 635                 640 


Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu Gly Gly Asp 
                645                 650                 655 


<210>  31
<211>  1965
<212>  DNA
<213>  Artificial

<220>
<223>  C-Cas9 encoding

<400>  31
tctggccagg gggacagtct tcacgagcac atcgctaatc ttgcaggtag cccagctatc     60

aaaaagggaa tactgcagac cgttaaggtc gtggatgaac tcgtcaaagt aatgggaagg    120

cataagcccg agaatatcgt tatcgagatg gcccgagaga accaaactac ccagaaggga    180

cagaagaaca gtagggaaag gatgaagagg attgaagagg gtataaaaga actggggtcc    240

caaatcctta aggaacaccc agttgaaaac acccagcttc agaatgagaa gctctacctg    300

tactacctgc agaacggcag ggacatgtac gtggatcagg aactggacat caatcggctc    360

tccgactacg acgtggatca tatcgtgccc cagtcttttc tcaaagatga ttctattgat    420

aataaagtgt tgacaagatc cgataaaaat agagggaaga gtgataacgt cccctcagaa    480

gaagttgtca agaaaatgaa aaattattgg cggcagctgc tgaacgccaa actgatcaca    540

caacggaagt tcgataatct gactaaggct gaacgaggtg gcctgtctga gttggataaa    600

gccggcttca tcaaaaggca gcttgttgag acacgccaga tcaccaagca cgtggcccaa    660

attctcgatt cacgcatgaa caccaagtac gatgaaaatg acaaactgat tcgagaggtg    720

aaagttatta ctctgaagtc taagctggtc tcagatttca gaaaggactt tcagttttat    780

aaggtgagag agatcaacaa ttaccaccat gcgcatgatg cctacctgaa tgcagtggta    840

ggcactgcac ttatcaaaaa atatcccaag cttgaatctg aatttgttta cggagactat    900

aaagtgtacg atgttaggaa aatgatcgca aagtctgagc aggaaatagg caaggccacc    960

gctaagtact tcttttacag caatattatg aattttttca agaccgagat tacactggcc   1020

aatggagaga ttcggaagcg accacttatc gaaacaaacg gagaaacagg agaaatcgtg   1080

tgggacaagg gtagggattt cgcgacagtc cggaaggtcc tgtccatgcc gcaggtgaac   1140

atcgttaaaa agaccgaagt acagaccgga ggcttctcca aggaaagtat cctcccgaaa   1200

aggaacagcg acaagctgat cgcacgcaaa aaagattggg accccaagaa atacggcgga   1260

ttcgattctc ctacagtcgc ttacagtgta ctggttgtgg ccaaagtgga gaaagggaag   1320

tctaaaaaac tcaaaagcgt caaggaactg ctgggcatca caatcatgga gcgatcaagc   1380

ttcgaaaaaa accccatcga ctttctcgag gcgaaaggat ataaagaggt caaaaaagac   1440

ctcatcatta agcttcccaa gtactctctc tttgagcttg aaaacggccg gaaacgaatg   1500

ctcgctagtg cgggcgagct gcagaaaggt aacgagctgg cactgccctc taaatacgtt   1560

aatttcttgt atctggccag ccactatgaa aagctcaaag ggtctcccga agataatgag   1620

cagaagcagc tgttcgtgga acaacacaaa cactaccttg atgagatcat cgagcaaata   1680

agcgaattct ccaaaagagt gatcctcgcc gacgctaacc tcgataaggt gctttctgct   1740

tacaataagc acagggataa gcccatcagg gagcaggcag aaaacattat ccacttgttt   1800

actctgacca acttgggcgc gcctgcagcc ttcaagtact tcgacaccac catagacaga   1860

aagcggtaca cctctacaaa ggaggtcctg gacgccacac tgattcatca gtcaattacg   1920

gggctctatg aaacaagaat cgacctctct cagctcggtg gagac                   1965


<210>  32
<211>  51
<212>  PRT
<213>  Artificial

<220>
<223>  C-Intein

<400>  32

Ala Ala Ala Cys Pro Glu Leu Arg Gln Leu Ala Gln Ser Asp Val Tyr 
1               5                   10                  15      


Trp Asp Pro Ile Val Ser Ile Glu Pro Asp Gly Val Glu Glu Val Phe 
            20                  25                  30          


Asp Leu Thr Val Pro Gly Pro His Asn Phe Val Ala Asn Asp Ile Ile 
        35                  40                  45              


Ala His Asn 
    50      


<210>  33
<211>  153
<212>  DNA
<213>  Artificial

<220>
<223>  C-Intein encoding

<400>  33
gcggcggcgt gcccggaact gcgtcagctg gcgcagagcg atgtgtattg ggatccgatt     60

gtgagcattg aaccggatgg cgtggaagaa gtgtttgatc tgaccgtgcc gggcccgcat    120

aactttgtgg cgaacgatat tattgcgcat aac                                 153


<210>  34
<211>  722
<212>  PRT
<213>  Artificial

<220>
<223>  Intein-SpCas9 C-fragment-SV40-NLS

<400>  34

Met Ala Ala Ala Cys Pro Glu Leu Arg Gln Leu Ala Gln Ser Asp Val 
1               5                   10                  15      


Tyr Trp Asp Pro Ile Val Ser Ile Glu Pro Asp Gly Val Glu Glu Val 
            20                  25                  30          


Phe Asp Leu Thr Val Pro Gly Pro His Asn Phe Val Ala Asn Asp Ile 
        35                  40                  45              


Ile Ala His Asn Ser Gly Gln Gly Asp Ser Leu His Glu His Ile Ala 
    50                  55                  60                  


Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly Ile Leu Gln Thr Val 
65                  70                  75                  80  


Lys Val Val Asp Glu Leu Val Lys Val Met Gly Arg His Lys Pro Glu 
                85                  90                  95      


Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln Thr Thr Gln Lys Gly 
            100                 105                 110         


Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile Glu Glu Gly Ile Lys 
        115                 120                 125             


Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro Val Glu Asn Thr Gln 
    130                 135                 140                 


Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly Arg Asp 
145                 150                 155                 160 


Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg Leu Ser Asp Tyr Asp 
                165                 170                 175     


Val Asp His Ile Val Pro Gln Ser Phe Leu Lys Asp Asp Ser Ile Asp 
            180                 185                 190         


Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg Gly Lys Ser Asp Asn 
        195                 200                 205             


Val Pro Ser Glu Glu Val Val Lys Lys Met Lys Asn Tyr Trp Arg Gln 
    210                 215                 220                 


Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys Phe Asp Asn Leu Thr 
225                 230                 235                 240 


Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp Lys Ala Gly Phe Ile 
                245                 250                 255     


Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr Lys His Val Ala Gln 
            260                 265                 270         


Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp Glu Asn Asp Lys Leu 
        275                 280                 285             


Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser Lys Leu Val Ser Asp 
    290                 295                 300                 


Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg Glu Ile Asn Asn Tyr 
305                 310                 315                 320 


His His Ala His Asp Ala Tyr Leu Asn Ala Val Val Gly Thr Ala Leu 
                325                 330                 335     


Ile Lys Lys Tyr Pro Lys Leu Glu Ser Glu Phe Val Tyr Gly Asp Tyr 
            340                 345                 350         


Lys Val Tyr Asp Val Arg Lys Met Ile Ala Lys Ser Glu Gln Glu Ile 
        355                 360                 365             


Gly Lys Ala Thr Ala Lys Tyr Phe Phe Tyr Ser Asn Ile Met Asn Phe 
    370                 375                 380                 


Phe Lys Thr Glu Ile Thr Leu Ala Asn Gly Glu Ile Arg Lys Arg Pro 
385                 390                 395                 400 


Leu Ile Glu Thr Asn Gly Glu Thr Gly Glu Ile Val Trp Asp Lys Gly 
                405                 410                 415     


Arg Asp Phe Ala Thr Val Arg Lys Val Leu Ser Met Pro Gln Val Asn 
            420                 425                 430         


Ile Val Lys Lys Thr Glu Val Gln Thr Gly Gly Phe Ser Lys Glu Ser 
        435                 440                 445             


Ile Leu Pro Lys Arg Asn Ser Asp Lys Leu Ile Ala Arg Lys Lys Asp 
    450                 455                 460                 


Trp Asp Pro Lys Lys Tyr Gly Gly Phe Asp Ser Pro Thr Val Ala Tyr 
465                 470                 475                 480 


Ser Val Leu Val Val Ala Lys Val Glu Lys Gly Lys Ser Lys Lys Leu 
                485                 490                 495     


Lys Ser Val Lys Glu Leu Leu Gly Ile Thr Ile Met Glu Arg Ser Ser 
            500                 505                 510         


Phe Glu Lys Asn Pro Ile Asp Phe Leu Glu Ala Lys Gly Tyr Lys Glu 
        515                 520                 525             


Val Lys Lys Asp Leu Ile Ile Lys Leu Pro Lys Tyr Ser Leu Phe Glu 
    530                 535                 540                 


Leu Glu Asn Gly Arg Lys Arg Met Leu Ala Ser Ala Gly Glu Leu Gln 
545                 550                 555                 560 


Lys Gly Asn Glu Leu Ala Leu Pro Ser Lys Tyr Val Asn Phe Leu Tyr 
                565                 570                 575     


Leu Ala Ser His Tyr Glu Lys Leu Lys Gly Ser Pro Glu Asp Asn Glu 
            580                 585                 590         


Gln Lys Gln Leu Phe Val Glu Gln His Lys His Tyr Leu Asp Glu Ile 
        595                 600                 605             


Ile Glu Gln Ile Ser Glu Phe Ser Lys Arg Val Ile Leu Ala Asp Ala 
    610                 615                 620                 


Asn Leu Asp Lys Val Leu Ser Ala Tyr Asn Lys His Arg Asp Lys Pro 
625                 630                 635                 640 


Ile Arg Glu Gln Ala Glu Asn Ile Ile His Leu Phe Thr Leu Thr Asn 
                645                 650                 655     


Leu Gly Ala Pro Ala Ala Phe Lys Tyr Phe Asp Thr Thr Ile Asp Arg 
            660                 665                 670         


Lys Arg Tyr Thr Ser Thr Lys Glu Val Leu Asp Ala Thr Leu Ile His 
        675                 680                 685             


Gln Ser Ile Thr Gly Leu Tyr Glu Thr Arg Ile Asp Leu Ser Gln Leu 
    690                 695                 700                 


Gly Gly Asp Ser Arg Ala Asp Pro Lys Lys Lys Arg Lys Val Ser Arg 
705                 710                 715                 720 


Ala Arg 
        


<210>  35
<211>  2166
<212>  DNA
<213>  Artificial

<220>
<223>  Intein-SpCas9 C-fragment-SV40-NLS encoding

<400>  35
atggcggcgg cgtgcccgga actgcgtcag ctggcgcaga gcgatgtgta ttgggatccg     60

attgtgagca ttgaaccgga tggcgtggaa gaagtgtttg atctgaccgt gccgggcccg    120

cataactttg tggcgaacga tattattgcg cataactctg gccaggggga cagtcttcac    180

gagcacatcg ctaatcttgc aggtagccca gctatcaaaa agggaatact gcagaccgtt    240

aaggtcgtgg atgaactcgt caaagtaatg ggaaggcata agcccgagaa tatcgttatc    300

gagatggccc gagagaacca aactacccag aagggacaga agaacagtag ggaaaggatg    360

aagaggattg aagagggtat aaaagaactg gggtcccaaa tccttaagga acacccagtt    420

gaaaacaccc agcttcagaa tgagaagctc tacctgtact acctgcagaa cggcagggac    480

atgtacgtgg atcaggaact ggacatcaat cggctctccg actacgacgt ggatcatatc    540

gtgccccagt cttttctcaa agatgattct attgataata aagtgttgac aagatccgat    600

aaaaatagag ggaagagtga taacgtcccc tcagaagaag ttgtcaagaa aatgaaaaat    660

tattggcggc agctgctgaa cgccaaactg atcacacaac ggaagttcga taatctgact    720

aaggctgaac gaggtggcct gtctgagttg gataaagccg gcttcatcaa aaggcagctt    780

gttgagacac gccagatcac caagcacgtg gcccaaattc tcgattcacg catgaacacc    840

aagtacgatg aaaatgacaa actgattcga gaggtgaaag ttattactct gaagtctaag    900

ctggtctcag atttcagaaa ggactttcag ttttataagg tgagagagat caacaattac    960

caccatgcgc atgatgccta cctgaatgca gtggtaggca ctgcacttat caaaaaatat   1020

cccaagcttg aatctgaatt tgtttacgga gactataaag tgtacgatgt taggaaaatg   1080

atcgcaaagt ctgagcagga aataggcaag gccaccgcta agtacttctt ttacagcaat   1140

attatgaatt ttttcaagac cgagattaca ctggccaatg gagagattcg gaagcgacca   1200

cttatcgaaa caaacggaga aacaggagaa atcgtgtggg acaagggtag ggatttcgcg   1260

acagtccgga aggtcctgtc catgccgcag gtgaacatcg ttaaaaagac cgaagtacag   1320

accggaggct tctccaagga aagtatcctc ccgaaaagga acagcgacaa gctgatcgca   1380

cgcaaaaaag attgggaccc caagaaatac ggcggattcg attctcctac agtcgcttac   1440

agtgtactgg ttgtggccaa agtggagaaa gggaagtcta aaaaactcaa aagcgtcaag   1500

gaactgctgg gcatcacaat catggagcga tcaagcttcg aaaaaaaccc catcgacttt   1560

ctcgaggcga aaggatataa agaggtcaaa aaagacctca tcattaagct tcccaagtac   1620

tctctctttg agcttgaaaa cggccggaaa cgaatgctcg ctagtgcggg cgagctgcag   1680

aaaggtaacg agctggcact gccctctaaa tacgttaatt tcttgtatct ggccagccac   1740

tatgaaaagc tcaaagggtc tcccgaagat aatgagcaga agcagctgtt cgtggaacaa   1800

cacaaacact accttgatga gatcatcgag caaataagcg aattctccaa aagagtgatc   1860

ctcgccgacg ctaacctcga taaggtgctt tctgcttaca ataagcacag ggataagccc   1920

atcagggagc aggcagaaaa cattatccac ttgtttactc tgaccaactt gggcgcgcct   1980

gcagccttca agtacttcga caccaccata gacagaaagc ggtacacctc tacaaaggag   2040

gtcctggacg ccacactgat tcatcagtca attacggggc tctatgaaac aagaatcgac   2100

ctctctcagc tcggtggaga cagcagggct gaccccaaga agaagaggaa ggtgtctcga   2160

gctcga                                                              2166


<210>  36
<211>  1367
<212>  PRT
<213>  Artificial

<220>
<223>  Cas9

<400>  36

Asp Lys Lys Tyr Ser Ile Gly Leu Asp Ile Gly Thr Asn Ser Val Gly 
1               5                   10                  15      


Trp Ala Val Ile Thr Asp Glu Tyr Lys Val Pro Ser Lys Lys Phe Lys 
            20                  25                  30          


Val Leu Gly Asn Thr Asp Arg His Ser Ile Lys Lys Asn Leu Ile Gly 
        35                  40                  45              


Ala Leu Leu Phe Asp Ser Gly Glu Thr Ala Glu Ala Thr Arg Leu Lys 
    50                  55                  60                  


Arg Thr Ala Arg Arg Arg Tyr Thr Arg Arg Lys Asn Arg Ile Cys Tyr 
65                  70                  75                  80  


Leu Gln Glu Ile Phe Ser Asn Glu Met Ala Lys Val Asp Asp Ser Phe 
                85                  90                  95      


Phe His Arg Leu Glu Glu Ser Phe Leu Val Glu Glu Asp Lys Lys His 
            100                 105                 110         


Glu Arg His Pro Ile Phe Gly Asn Ile Val Asp Glu Val Ala Tyr His 
        115                 120                 125             


Glu Lys Tyr Pro Thr Ile Tyr His Leu Arg Lys Lys Leu Val Asp Ser 
    130                 135                 140                 


Thr Asp Lys Ala Asp Leu Arg Leu Ile Tyr Leu Ala Leu Ala His Met 
145                 150                 155                 160 


Ile Lys Phe Arg Gly His Phe Leu Ile Glu Gly Asp Leu Asn Pro Asp 
                165                 170                 175     


Asn Ser Asp Val Asp Lys Leu Phe Ile Gln Leu Val Gln Thr Tyr Asn 
            180                 185                 190         


Gln Leu Phe Glu Glu Asn Pro Ile Asn Ala Ser Gly Val Asp Ala Lys 
        195                 200                 205             


Ala Ile Leu Ser Ala Arg Leu Ser Lys Ser Arg Arg Leu Glu Asn Leu 
    210                 215                 220                 


Ile Ala Gln Leu Pro Gly Glu Lys Lys Asn Gly Leu Phe Gly Asn Leu 
225                 230                 235                 240 


Ile Ala Leu Ser Leu Gly Leu Thr Pro Asn Phe Lys Ser Asn Phe Asp 
                245                 250                 255     


Leu Ala Glu Asp Ala Lys Leu Gln Leu Ser Lys Asp Thr Tyr Asp Asp 
            260                 265                 270         


Asp Leu Asp Asn Leu Leu Ala Gln Ile Gly Asp Gln Tyr Ala Asp Leu 
        275                 280                 285             


Phe Leu Ala Ala Lys Asn Leu Ser Asp Ala Ile Leu Leu Ser Asp Ile 
    290                 295                 300                 


Leu Arg Val Asn Thr Glu Ile Thr Lys Ala Pro Leu Ser Ala Ser Met 
305                 310                 315                 320 


Ile Lys Arg Tyr Asp Glu His His Gln Asp Leu Thr Leu Leu Lys Ala 
                325                 330                 335     


Leu Val Arg Gln Gln Leu Pro Glu Lys Tyr Lys Glu Ile Phe Phe Asp 
            340                 345                 350         


Gln Ser Lys Asn Gly Tyr Ala Gly Tyr Ile Asp Gly Gly Ala Ser Gln 
        355                 360                 365             


Glu Glu Phe Tyr Lys Phe Ile Lys Pro Ile Leu Glu Lys Met Asp Gly 
    370                 375                 380                 


Thr Glu Glu Leu Leu Val Lys Leu Asn Arg Glu Asp Leu Leu Arg Lys 
385                 390                 395                 400 


Gln Arg Thr Phe Asp Asn Gly Ser Ile Pro His Gln Ile His Leu Gly 
                405                 410                 415     


Glu Leu His Ala Ile Leu Arg Arg Gln Glu Asp Phe Tyr Pro Phe Leu 
            420                 425                 430         


Lys Asp Asn Arg Glu Lys Ile Glu Lys Ile Leu Thr Phe Arg Ile Pro 
        435                 440                 445             


Tyr Tyr Val Gly Pro Leu Ala Arg Gly Asn Ser Arg Phe Ala Trp Met 
    450                 455                 460                 


Thr Arg Lys Ser Glu Glu Thr Ile Thr Pro Trp Asn Phe Glu Glu Val 
465                 470                 475                 480 


Val Asp Lys Gly Ala Ser Ala Gln Ser Phe Ile Glu Arg Met Thr Asn 
                485                 490                 495     


Phe Asp Lys Asn Leu Pro Asn Glu Lys Val Leu Pro Lys His Ser Leu 
            500                 505                 510         


Leu Tyr Glu Tyr Phe Thr Val Tyr Asn Glu Leu Thr Lys Val Lys Tyr 
        515                 520                 525             


Val Thr Glu Gly Met Arg Lys Pro Ala Phe Leu Ser Gly Glu Gln Lys 
    530                 535                 540                 


Lys Ala Ile Val Asp Leu Leu Phe Lys Thr Asn Arg Lys Val Thr Val 
545                 550                 555                 560 


Lys Gln Leu Lys Glu Asp Tyr Phe Lys Lys Ile Glu Cys Phe Asp Ser 
                565                 570                 575     


Val Glu Ile Ser Gly Val Glu Asp Arg Phe Asn Ala Ser Leu Gly Thr 
            580                 585                 590         


Tyr His Asp Leu Leu Lys Ile Ile Lys Asp Lys Asp Phe Leu Asp Asn 
        595                 600                 605             


Glu Glu Asn Glu Asp Ile Leu Glu Asp Ile Val Leu Thr Leu Thr Leu 
    610                 615                 620                 


Phe Glu Asp Arg Glu Met Ile Glu Glu Arg Leu Lys Thr Tyr Ala His 
625                 630                 635                 640 


Leu Phe Asp Asp Lys Val Met Lys Gln Leu Lys Arg Arg Arg Tyr Thr 
                645                 650                 655     


Gly Trp Gly Arg Leu Ser Arg Lys Leu Ile Asn Gly Ile Arg Asp Lys 
            660                 665                 670         


Gln Ser Gly Lys Thr Ile Leu Asp Phe Leu Lys Ser Asp Gly Phe Ala 
        675                 680                 685             


Asn Arg Asn Phe Met Gln Leu Ile His Asp Asp Ser Leu Thr Phe Lys 
    690                 695                 700                 


Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser Leu His 
705                 710                 715                 720 


Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys Gly Ile 
                725                 730                 735     


Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met Gly Arg 
            740                 745                 750         


His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn Gln Thr 
        755                 760                 765             


Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg Ile Glu 
    770                 775                 780                 


Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His Pro Val 
785                 790                 795                 800 


Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr Leu Gln 
                805                 810                 815     


Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn Arg Leu 
            820                 825                 830         


Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln Ser Phe Leu Lys Asp 
        835                 840                 845             


Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn Arg Gly 
    850                 855                 860                 


Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met Lys Asn 
865                 870                 875                 880 


Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg Lys Phe 
                885                 890                 895     


Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu Asp Lys 
            900                 905                 910         


Ala Gly Phe Ile Lys Arg Gln Leu Val Glu Thr Arg Gln Ile Thr Lys 
        915                 920                 925             


His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr Asp Glu 
    930                 935                 940                 


Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys Ser Lys 
945                 950                 955                 960 


Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val Arg Glu 
                965                 970                 975     


Ile Asn Asn Tyr His His Ala His Asp Ala Tyr Leu Asn Ala Val Val 
            980                 985                 990         


Gly Thr Ala Leu Ile Lys Lys Tyr  Pro Lys Leu Glu Ser  Glu Phe Val 
        995                 1000                 1005             


Tyr Gly  Asp Tyr Lys Val Tyr  Asp Val Arg Lys Met  Ile Ala Lys 
    1010                 1015                 1020             


Ser Glu  Gln Glu Ile Gly Lys  Ala Thr Ala Lys Tyr  Phe Phe Tyr 
    1025                 1030                 1035             


Ser Asn  Ile Met Asn Phe Phe  Lys Thr Glu Ile Thr  Leu Ala Asn 
    1040                 1045                 1050             


Gly Glu  Ile Arg Lys Arg Pro  Leu Ile Glu Thr Asn  Gly Glu Thr 
    1055                 1060                 1065             


Gly Glu  Ile Val Trp Asp Lys  Gly Arg Asp Phe Ala  Thr Val Arg 
    1070                 1075                 1080             


Lys Val  Leu Ser Met Pro Gln  Val Asn Ile Val Lys  Lys Thr Glu 
    1085                 1090                 1095             


Val Gln  Thr Gly Gly Phe Ser  Lys Glu Ser Ile Leu  Pro Lys Arg 
    1100                 1105                 1110             


Asn Ser  Asp Lys Leu Ile Ala  Arg Lys Lys Asp Trp  Asp Pro Lys 
    1115                 1120                 1125             


Lys Tyr  Gly Gly Phe Asp Ser  Pro Thr Val Ala Tyr  Ser Val Leu 
    1130                 1135                 1140             


Val Val  Ala Lys Val Glu Lys  Gly Lys Ser Lys Lys  Leu Lys Ser 
    1145                 1150                 1155             


Val Lys  Glu Leu Leu Gly Ile  Thr Ile Met Glu Arg  Ser Ser Phe 
    1160                 1165                 1170             


Glu Lys  Asn Pro Ile Asp Phe  Leu Glu Ala Lys Gly  Tyr Lys Glu 
    1175                 1180                 1185             


Val Lys  Lys Asp Leu Ile Ile  Lys Leu Pro Lys Tyr  Ser Leu Phe 
    1190                 1195                 1200             


Glu Leu  Glu Asn Gly Arg Lys  Arg Met Leu Ala Ser  Ala Gly Glu 
    1205                 1210                 1215             


Leu Gln  Lys Gly Asn Glu Leu  Ala Leu Pro Ser Lys  Tyr Val Asn 
    1220                 1225                 1230             


Phe Leu  Tyr Leu Ala Ser His  Tyr Glu Lys Leu Lys  Gly Ser Pro 
    1235                 1240                 1245             


Glu Asp  Asn Glu Gln Lys Gln  Leu Phe Val Glu Gln  His Lys His 
    1250                 1255                 1260             


Tyr Leu  Asp Glu Ile Ile Glu  Gln Ile Ser Glu Phe  Ser Lys Arg 
    1265                 1270                 1275             


Val Ile  Leu Ala Asp Ala Asn  Leu Asp Lys Val Leu  Ser Ala Tyr 
    1280                 1285                 1290             


Asn Lys  His Arg Asp Lys Pro  Ile Arg Glu Gln Ala  Glu Asn Ile 
    1295                 1300                 1305             


Ile His  Leu Phe Thr Leu Thr  Asn Leu Gly Ala Pro  Ala Ala Phe 
    1310                 1315                 1320             


Lys Tyr  Phe Asp Thr Thr Ile  Asp Arg Lys Arg Tyr  Thr Ser Thr 
    1325                 1330                 1335             


Lys Glu  Val Leu Asp Ala Thr  Leu Ile His Gln Ser  Ile Thr Gly 
    1340                 1345                 1350             


Leu Tyr  Glu Thr Arg Ile Asp  Leu Ser Gln Leu Gly  Gly Asp 
    1355                 1360                 1365         


<210>  37
<211>  4101
<212>  DNA
<213>  Artificial

<220>
<223>  Cas encoding

<400>  37
gacaagaagt acagcatcgg cctggacatc ggcaccaact ctgtgggctg ggccgtgatc     60

accgacgagt acaaggtgcc cagcaagaaa ttcaaggtgc tgggcaacac cgaccggcac    120

agcatcaaga agaacctgat cggagccctg ctgttcgaca gcggcgaaac agccgaggcc    180

acccggctga agagaaccgc cagaagaaga tacaccagac ggaagaaccg gatctgctat    240

ctgcaagaga tcttcagcaa cgagatggcc aaggtggacg acagcttctt ccacagactg    300

gaagagtcct tcctggtgga agaggataag aagcacgagc ggcaccccat cttcggcaac    360

atcgtggacg aggtggccta ccacgagaag taccccacca tctaccacct gagaaagaaa    420

ctggtggaca gcaccgacaa ggccgacctg cggctgatct atctggccct ggcccacatg    480

atcaagttcc ggggccactt cctgatcgag ggcgacctga accccgacaa cagcgacgtg    540

gacaagctgt tcatccagct ggtgcagacc tacaaccagc tgttcgagga aaaccccatc    600

aacgccagcg gcgtggacgc caaggccatc ctgtctgcca gactgagcaa gagcagacgg    660

ctggaaaatc tgatcgccca gctgcccggc gagaagaaga atggcctgtt cggaaacctg    720

attgccctga gcctgggcct gacccccaac ttcaagagca acttcgacct ggccgaggat    780

gccaaactgc agctgagcaa ggacacctac gacgacgacc tggacaacct gctggcccag    840

atcggcgacc agtacgccga cctgtttctg gccgccaaga acctgtccga cgccatcctg    900

ctgagcgaca tcctgagagt gaacaccgag atcaccaagg cccccctgag cgcctctatg    960

atcaagagat acgacgagca ccaccaggac ctgaccctgc tgaaagctct cgtgcggcag   1020

cagctgcctg agaagtacaa agagattttc ttcgaccaga gcaagaacgg ctacgccggc   1080

tacattgacg gcggagccag ccaggaagag ttctacaagt tcatcaagcc catcctggaa   1140

aagatggacg gcaccgagga actgctcgtg aagctgaaca gagaggacct gctgcggaag   1200

cagcggacct tcgacaacgg cagcatcccc caccagatcc acctgggaga gctgcacgcc   1260

attctgcggc ggcaggaaga tttttaccca ttcctgaagg acaaccggga aaagatcgag   1320

aagatcctga ccttccgcat cccctactac gtgggccctc tggccagggg aaacagcaga   1380

ttcgcctgga tgaccagaaa gagcgaggaa accatcaccc cctggaactt cgaggaagtg   1440

gtggacaagg gcgcttccgc ccagagcttc atcgagcgga tgaccaactt cgataagaac   1500

ctgcccaacg agaaggtgct gcccaagcac agcctgctgt acgagtactt caccgtgtat   1560

aacgagctga ccaaagtgaa atacgtgacc gagggaatga gaaagcccgc cttcctgagc   1620

ggcgagcaga aaaaggccat cgtggacctg ctgttcaaga ccaaccggaa agtgaccgtg   1680

aagcagctga aagaggacta cttcaagaaa atcgagtgct tcgactccgt ggaaatctcc   1740

ggcgtggaag atcggttcaa cgcctccctg ggcacatacc acgatctgct gaaaattatc   1800

aaggacaagg acttcctgga caatgaggaa aacgaggaca ttctggaaga tatcgtgctg   1860

accctgacac tgtttgagga cagagagatg atcgaggaac ggctgaaaac ctatgcccac   1920

ctgttcgacg acaaagtgat gaagcagctg aagcggcgga gatacaccgg ctggggcagg   1980

ctgagccgga agctgatcaa cggcatccgg gacaagcagt ccggcaagac aatcctggat   2040

ttcctgaagt ccgacggctt cgccaacaga aacttcatgc agctgatcca cgacgacagc   2100

ctgaccttta aagaggacat ccagaaagcc caggtgtccg gccagggcga tagcctgcac   2160

gagcacattg ccaatctggc cggcagcccc gccattaaga agggcatcct gcagacagtg   2220

aaggtggtgg acgagctcgt gaaagtgatg ggccggcaca agcccgagaa catcgtgatc   2280

gaaatggcca gagagaacca gaccacccag aagggacaga agaacagccg cgagagaatg   2340

aagcggatcg aagagggcat caaagagctg ggcagccaga tcctgaaaga acaccccgtg   2400

gaaaacaccc agctgcagaa cgagaagctg tacctgtact acctgcagaa tgggcgggat   2460

atgtacgtgg accaggaact ggacatcaac cggctgtccg actacgatgt ggaccatatc   2520

gtgcctcaga gctttctgaa ggacgactcc atcgacaaca aggtgctgac cagaagcgac   2580

aagaaccggg gcaagagcga caacgtgccc tccgaagagg tcgtgaagaa gatgaagaac   2640

tactggcggc agctgctgaa cgccaagctg attacccaga gaaagttcga caatctgacc   2700

aaggccgaga gaggcggcct gagcgaactg gataaggccg gcttcatcaa gagacagctg   2760

gtggaaaccc ggcagatcac aaagcacgtg gcacagatcc tggactcccg gatgaacact   2820

aagtacgacg agaatgacaa gctgatccgg gaagtgaaag tgatcaccct gaagtccaag   2880

ctggtgtccg atttccggaa ggatttccag ttttacaaag tgcgcgagat caacaactac   2940

caccacgccc acgacgccta cctgaacgcc gtcgtgggaa ccgccctgat caaaaagtac   3000

cctaagctgg aaagcgagtt cgtgtacggc gactacaagg tgtacgacgt gcggaagatg   3060

atcgccaaga gcgagcagga aatcggcaag gctaccgcca agtacttctt ctacagcaac   3120

atcatgaact ttttcaagac cgagattacc ctggccaacg gcgagatccg gaagcggcct   3180

ctgatcgaga caaacggcga aaccggggag atcgtgtggg ataagggccg ggattttgcc   3240

accgtgcgga aagtgctgag catgccccaa gtgaatatcg tgaaaaagac cgaggtgcag   3300

acaggcggct tcagcaaaga gtctatcctg cccaagagga acagcgataa gctgatcgcc   3360

agaaagaagg actgggaccc taagaagtac ggcggcttcg acagccccac cgtggcctat   3420

tctgtgctgg tggtggccaa agtggaaaag ggcaagtcca agaaactgaa gagtgtgaaa   3480

gagctgctgg ggatcaccat catggaaaga agcagcttcg agaagaatcc catcgacttt   3540

ctggaagcca agggctacaa agaagtgaaa aaggacctga tcatcaagct gcctaagtac   3600

tccctgttcg agctggaaaa cggccggaag agaatgctgg cctctgccgg cgaactgcag   3660

aagggaaacg aactggccct gccctccaaa tatgtgaact tcctgtacct ggccagccac   3720

tatgagaagc tgaagggctc ccccgaggat aatgagcaga aacagctgtt tgtggaacag   3780

cacaagcact acctggacga gatcatcgag cagatcagcg agttctccaa gagagtgatc   3840

ctggccgacg ctaatctgga caaagtgctg tccgcctaca acaagcaccg ggataagccc   3900

atcagagagc aggccgagaa tatcatccac ctgtttaccc tgaccaatct gggagcccct   3960

gccgccttca agtactttga caccaccatc gaccggaaga ggtacaccag caccaaagag   4020

gtgctggacg ccaccctgat ccaccagagc atcaccggcc tgtacgagac acggatcgac   4080

ctgtctcagc tgggaggcga c                                             4101


<210>  38
<211>  1425
<212>  PRT
<213>  Artificial

<220>
<223>  3xFLAG-NLS-SpCas9-NLS

<400>  38

Met Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp 
1               5                   10                  15      


Tyr Lys Asp Asp Asp Asp Lys Met Ala Pro Lys Lys Lys Arg Lys Val 
            20                  25                  30          


Gly Ile His Gly Val Pro Ala Ala Asp Lys Lys Tyr Ser Ile Gly Leu 
        35                  40                  45              


Asp Ile Gly Thr Asn Ser Val Gly Trp Ala Val Ile Thr Asp Glu Tyr 
    50                  55                  60                  


Lys Val Pro Ser Lys Lys Phe Lys Val Leu Gly Asn Thr Asp Arg His 
65                  70                  75                  80  


Ser Ile Lys Lys Asn Leu Ile Gly Ala Leu Leu Phe Asp Ser Gly Glu 
                85                  90                  95      


Thr Ala Glu Ala Thr Arg Leu Lys Arg Thr Ala Arg Arg Arg Tyr Thr 
            100                 105                 110         


Arg Arg Lys Asn Arg Ile Cys Tyr Leu Gln Glu Ile Phe Ser Asn Glu 
        115                 120                 125             


Met Ala Lys Val Asp Asp Ser Phe Phe His Arg Leu Glu Glu Ser Phe 
    130                 135                 140                 


Leu Val Glu Glu Asp Lys Lys His Glu Arg His Pro Ile Phe Gly Asn 
145                 150                 155                 160 


Ile Val Asp Glu Val Ala Tyr His Glu Lys Tyr Pro Thr Ile Tyr His 
                165                 170                 175     


Leu Arg Lys Lys Leu Val Asp Ser Thr Asp Lys Ala Asp Leu Arg Leu 
            180                 185                 190         


Ile Tyr Leu Ala Leu Ala His Met Ile Lys Phe Arg Gly His Phe Leu 
        195                 200                 205             


Ile Glu Gly Asp Leu Asn Pro Asp Asn Ser Asp Val Asp Lys Leu Phe 
    210                 215                 220                 


Ile Gln Leu Val Gln Thr Tyr Asn Gln Leu Phe Glu Glu Asn Pro Ile 
225                 230                 235                 240 


Asn Ala Ser Gly Val Asp Ala Lys Ala Ile Leu Ser Ala Arg Leu Ser 
                245                 250                 255     


Lys Ser Arg Arg Leu Glu Asn Leu Ile Ala Gln Leu Pro Gly Glu Lys 
            260                 265                 270         


Lys Asn Gly Leu Phe Gly Asn Leu Ile Ala Leu Ser Leu Gly Leu Thr 
        275                 280                 285             


Pro Asn Phe Lys Ser Asn Phe Asp Leu Ala Glu Asp Ala Lys Leu Gln 
    290                 295                 300                 


Leu Ser Lys Asp Thr Tyr Asp Asp Asp Leu Asp Asn Leu Leu Ala Gln 
305                 310                 315                 320 


Ile Gly Asp Gln Tyr Ala Asp Leu Phe Leu Ala Ala Lys Asn Leu Ser 
                325                 330                 335     


Asp Ala Ile Leu Leu Ser Asp Ile Leu Arg Val Asn Thr Glu Ile Thr 
            340                 345                 350         


Lys Ala Pro Leu Ser Ala Ser Met Ile Lys Arg Tyr Asp Glu His His 
        355                 360                 365             


Gln Asp Leu Thr Leu Leu Lys Ala Leu Val Arg Gln Gln Leu Pro Glu 
    370                 375                 380                 


Lys Tyr Lys Glu Ile Phe Phe Asp Gln Ser Lys Asn Gly Tyr Ala Gly 
385                 390                 395                 400 


Tyr Ile Asp Gly Gly Ala Ser Gln Glu Glu Phe Tyr Lys Phe Ile Lys 
                405                 410                 415     


Pro Ile Leu Glu Lys Met Asp Gly Thr Glu Glu Leu Leu Val Lys Leu 
            420                 425                 430         


Asn Arg Glu Asp Leu Leu Arg Lys Gln Arg Thr Phe Asp Asn Gly Ser 
        435                 440                 445             


Ile Pro His Gln Ile His Leu Gly Glu Leu His Ala Ile Leu Arg Arg 
    450                 455                 460                 


Gln Glu Asp Phe Tyr Pro Phe Leu Lys Asp Asn Arg Glu Lys Ile Glu 
465                 470                 475                 480 


Lys Ile Leu Thr Phe Arg Ile Pro Tyr Tyr Val Gly Pro Leu Ala Arg 
                485                 490                 495     


Gly Asn Ser Arg Phe Ala Trp Met Thr Arg Lys Ser Glu Glu Thr Ile 
            500                 505                 510         


Thr Pro Trp Asn Phe Glu Glu Val Val Asp Lys Gly Ala Ser Ala Gln 
        515                 520                 525             


Ser Phe Ile Glu Arg Met Thr Asn Phe Asp Lys Asn Leu Pro Asn Glu 
    530                 535                 540                 


Lys Val Leu Pro Lys His Ser Leu Leu Tyr Glu Tyr Phe Thr Val Tyr 
545                 550                 555                 560 


Asn Glu Leu Thr Lys Val Lys Tyr Val Thr Glu Gly Met Arg Lys Pro 
                565                 570                 575     


Ala Phe Leu Ser Gly Glu Gln Lys Lys Ala Ile Val Asp Leu Leu Phe 
            580                 585                 590         


Lys Thr Asn Arg Lys Val Thr Val Lys Gln Leu Lys Glu Asp Tyr Phe 
        595                 600                 605             


Lys Lys Ile Glu Cys Phe Asp Ser Val Glu Ile Ser Gly Val Glu Asp 
    610                 615                 620                 


Arg Phe Asn Ala Ser Leu Gly Thr Tyr His Asp Leu Leu Lys Ile Ile 
625                 630                 635                 640 


Lys Asp Lys Asp Phe Leu Asp Asn Glu Glu Asn Glu Asp Ile Leu Glu 
                645                 650                 655     


Asp Ile Val Leu Thr Leu Thr Leu Phe Glu Asp Arg Glu Met Ile Glu 
            660                 665                 670         


Glu Arg Leu Lys Thr Tyr Ala His Leu Phe Asp Asp Lys Val Met Lys 
        675                 680                 685             


Gln Leu Lys Arg Arg Arg Tyr Thr Gly Trp Gly Arg Leu Ser Arg Lys 
    690                 695                 700                 


Leu Ile Asn Gly Ile Arg Asp Lys Gln Ser Gly Lys Thr Ile Leu Asp 
705                 710                 715                 720 


Phe Leu Lys Ser Asp Gly Phe Ala Asn Arg Asn Phe Met Gln Leu Ile 
                725                 730                 735     


His Asp Asp Ser Leu Thr Phe Lys Glu Asp Ile Gln Lys Ala Gln Val 
            740                 745                 750         


Ser Gly Gln Gly Asp Ser Leu His Glu His Ile Ala Asn Leu Ala Gly 
        755                 760                 765             


Ser Pro Ala Ile Lys Lys Gly Ile Leu Gln Thr Val Lys Val Val Asp 
    770                 775                 780                 


Glu Leu Val Lys Val Met Gly Arg His Lys Pro Glu Asn Ile Val Ile 
785                 790                 795                 800 


Glu Met Ala Arg Glu Asn Gln Thr Thr Gln Lys Gly Gln Lys Asn Ser 
                805                 810                 815     


Arg Glu Arg Met Lys Arg Ile Glu Glu Gly Ile Lys Glu Leu Gly Ser 
            820                 825                 830         


Gln Ile Leu Lys Glu His Pro Val Glu Asn Thr Gln Leu Gln Asn Glu 
        835                 840                 845             


Lys Leu Tyr Leu Tyr Tyr Leu Gln Asn Gly Arg Asp Met Tyr Val Asp 
    850                 855                 860                 


Gln Glu Leu Asp Ile Asn Arg Leu Ser Asp Tyr Asp Val Asp His Ile 
865                 870                 875                 880 


Val Pro Gln Ser Phe Leu Lys Asp Asp Ser Ile Asp Asn Lys Val Leu 
                885                 890                 895     


Thr Arg Ser Asp Lys Asn Arg Gly Lys Ser Asp Asn Val Pro Ser Glu 
            900                 905                 910         


Glu Val Val Lys Lys Met Lys Asn Tyr Trp Arg Gln Leu Leu Asn Ala 
        915                 920                 925             


Lys Leu Ile Thr Gln Arg Lys Phe Asp Asn Leu Thr Lys Ala Glu Arg 
    930                 935                 940                 


Gly Gly Leu Ser Glu Leu Asp Lys Ala Gly Phe Ile Lys Arg Gln Leu 
945                 950                 955                 960 


Val Glu Thr Arg Gln Ile Thr Lys His Val Ala Gln Ile Leu Asp Ser 
                965                 970                 975     


Arg Met Asn Thr Lys Tyr Asp Glu Asn Asp Lys Leu Ile Arg Glu Val 
            980                 985                 990         


Lys Val Ile Thr Leu Lys Ser Lys  Leu Val Ser Asp Phe  Arg Lys Asp 
        995                 1000                 1005             


Phe Gln  Phe Tyr Lys Val Arg  Glu Ile Asn Asn Tyr  His His Ala 
    1010                 1015                 1020             


His Asp  Ala Tyr Leu Asn Ala  Val Val Gly Thr Ala  Leu Ile Lys 
    1025                 1030                 1035             


Lys Tyr  Pro Lys Leu Glu Ser  Glu Phe Val Tyr Gly  Asp Tyr Lys 
    1040                 1045                 1050             


Val Tyr  Asp Val Arg Lys Met  Ile Ala Lys Ser Glu  Gln Glu Ile 
    1055                 1060                 1065             


Gly Lys  Ala Thr Ala Lys Tyr  Phe Phe Tyr Ser Asn  Ile Met Asn 
    1070                 1075                 1080             


Phe Phe  Lys Thr Glu Ile Thr  Leu Ala Asn Gly Glu  Ile Arg Lys 
    1085                 1090                 1095             


Arg Pro  Leu Ile Glu Thr Asn  Gly Glu Thr Gly Glu  Ile Val Trp 
    1100                 1105                 1110             


Asp Lys  Gly Arg Asp Phe Ala  Thr Val Arg Lys Val  Leu Ser Met 
    1115                 1120                 1125             


Pro Gln  Val Asn Ile Val Lys  Lys Thr Glu Val Gln  Thr Gly Gly 
    1130                 1135                 1140             


Phe Ser  Lys Glu Ser Ile Leu  Pro Lys Arg Asn Ser  Asp Lys Leu 
    1145                 1150                 1155             


Ile Ala  Arg Lys Lys Asp Trp  Asp Pro Lys Lys Tyr  Gly Gly Phe 
    1160                 1165                 1170             


Asp Ser  Pro Thr Val Ala Tyr  Ser Val Leu Val Val  Ala Lys Val 
    1175                 1180                 1185             


Glu Lys  Gly Lys Ser Lys Lys  Leu Lys Ser Val Lys  Glu Leu Leu 
    1190                 1195                 1200             


Gly Ile  Thr Ile Met Glu Arg  Ser Ser Phe Glu Lys  Asn Pro Ile 
    1205                 1210                 1215             


Asp Phe  Leu Glu Ala Lys Gly  Tyr Lys Glu Val Lys  Lys Asp Leu 
    1220                 1225                 1230             


Ile Ile  Lys Leu Pro Lys Tyr  Ser Leu Phe Glu Leu  Glu Asn Gly 
    1235                 1240                 1245             


Arg Lys  Arg Met Leu Ala Ser  Ala Gly Glu Leu Gln  Lys Gly Asn 
    1250                 1255                 1260             


Glu Leu  Ala Leu Pro Ser Lys  Tyr Val Asn Phe Leu  Tyr Leu Ala 
    1265                 1270                 1275             


Ser His  Tyr Glu Lys Leu Lys  Gly Ser Pro Glu Asp  Asn Glu Gln 
    1280                 1285                 1290             


Lys Gln  Leu Phe Val Glu Gln  His Lys His Tyr Leu  Asp Glu Ile 
    1295                 1300                 1305             


Ile Glu  Gln Ile Ser Glu Phe  Ser Lys Arg Val Ile  Leu Ala Asp 
    1310                 1315                 1320             


Ala Asn  Leu Asp Lys Val Leu  Ser Ala Tyr Asn Lys  His Arg Asp 
    1325                 1330                 1335             


Lys Pro  Ile Arg Glu Gln Ala  Glu Asn Ile Ile His  Leu Phe Thr 
    1340                 1345                 1350             


Leu Thr  Asn Leu Gly Ala Pro  Ala Ala Phe Lys Tyr  Phe Asp Thr 
    1355                 1360                 1365             


Thr Ile  Asp Arg Lys Arg Tyr  Thr Ser Thr Lys Glu  Val Leu Asp 
    1370                 1375                 1380             


Ala Thr  Leu Ile His Gln Ser  Ile Thr Gly Leu Tyr  Glu Thr Arg 
    1385                 1390                 1395             


Ile Asp  Leu Ser Gln Leu Gly  Gly Asp Lys Arg Pro  Ala Ala Thr 
    1400                 1405                 1410             


Lys Lys  Ala Gly Gln Ala Lys  Lys Lys Lys Glu Phe  
    1415                 1420                 1425 


<210>  39
<211>  4275
<212>  DNA
<213>  Artificial

<220>
<223>  3xFLAG-NLS-SpCas9-NLS encoding

<400>  39
atggactata aggaccacga cggagactac aaggatcatg atattgatta caaagacgat     60

gacgataaga tggccccaaa gaagaagcgg aaggtcggta tccacggagt cccagcagcc    120

gacaagaagt acagcatcgg cctggacatc ggcaccaact ctgtgggctg ggccgtgatc    180

accgacgagt acaaggtgcc cagcaagaaa ttcaaggtgc tgggcaacac cgaccggcac    240

agcatcaaga agaacctgat cggagccctg ctgttcgaca gcggcgaaac agccgaggcc    300

acccggctga agagaaccgc cagaagaaga tacaccagac ggaagaaccg gatctgctat    360

ctgcaagaga tcttcagcaa cgagatggcc aaggtggacg acagcttctt ccacagactg    420

gaagagtcct tcctggtgga agaggataag aagcacgagc ggcaccccat cttcggcaac    480

atcgtggacg aggtggccta ccacgagaag taccccacca tctaccacct gagaaagaaa    540

ctggtggaca gcaccgacaa ggccgacctg cggctgatct atctggccct ggcccacatg    600

atcaagttcc ggggccactt cctgatcgag ggcgacctga accccgacaa cagcgacgtg    660

gacaagctgt tcatccagct ggtgcagacc tacaaccagc tgttcgagga aaaccccatc    720

aacgccagcg gcgtggacgc caaggccatc ctgtctgcca gactgagcaa gagcagacgg    780

ctggaaaatc tgatcgccca gctgcccggc gagaagaaga atggcctgtt cggaaacctg    840

attgccctga gcctgggcct gacccccaac ttcaagagca acttcgacct ggccgaggat    900

gccaaactgc agctgagcaa ggacacctac gacgacgacc tggacaacct gctggcccag    960

atcggcgacc agtacgccga cctgtttctg gccgccaaga acctgtccga cgccatcctg   1020

ctgagcgaca tcctgagagt gaacaccgag atcaccaagg cccccctgag cgcctctatg   1080

atcaagagat acgacgagca ccaccaggac ctgaccctgc tgaaagctct cgtgcggcag   1140

cagctgcctg agaagtacaa agagattttc ttcgaccaga gcaagaacgg ctacgccggc   1200

tacattgacg gcggagccag ccaggaagag ttctacaagt tcatcaagcc catcctggaa   1260

aagatggacg gcaccgagga actgctcgtg aagctgaaca gagaggacct gctgcggaag   1320

cagcggacct tcgacaacgg cagcatcccc caccagatcc acctgggaga gctgcacgcc   1380

attctgcggc ggcaggaaga tttttaccca ttcctgaagg acaaccggga aaagatcgag   1440

aagatcctga ccttccgcat cccctactac gtgggccctc tggccagggg aaacagcaga   1500

ttcgcctgga tgaccagaaa gagcgaggaa accatcaccc cctggaactt cgaggaagtg   1560

gtggacaagg gcgcttccgc ccagagcttc atcgagcgga tgaccaactt cgataagaac   1620

ctgcccaacg agaaggtgct gcccaagcac agcctgctgt acgagtactt caccgtgtat   1680

aacgagctga ccaaagtgaa atacgtgacc gagggaatga gaaagcccgc cttcctgagc   1740

ggcgagcaga aaaaggccat cgtggacctg ctgttcaaga ccaaccggaa agtgaccgtg   1800

aagcagctga aagaggacta cttcaagaaa atcgagtgct tcgactccgt ggaaatctcc   1860

ggcgtggaag atcggttcaa cgcctccctg ggcacatacc acgatctgct gaaaattatc   1920

aaggacaagg acttcctgga caatgaggaa aacgaggaca ttctggaaga tatcgtgctg   1980

accctgacac tgtttgagga cagagagatg atcgaggaac ggctgaaaac ctatgcccac   2040

ctgttcgacg acaaagtgat gaagcagctg aagcggcgga gatacaccgg ctggggcagg   2100

ctgagccgga agctgatcaa cggcatccgg gacaagcagt ccggcaagac aatcctggat   2160

ttcctgaagt ccgacggctt cgccaacaga aacttcatgc agctgatcca cgacgacagc   2220

ctgaccttta aagaggacat ccagaaagcc caggtgtccg gccagggcga tagcctgcac   2280

gagcacattg ccaatctggc cggcagcccc gccattaaga agggcatcct gcagacagtg   2340

aaggtggtgg acgagctcgt gaaagtgatg ggccggcaca agcccgagaa catcgtgatc   2400

gaaatggcca gagagaacca gaccacccag aagggacaga agaacagccg cgagagaatg   2460

aagcggatcg aagagggcat caaagagctg ggcagccaga tcctgaaaga acaccccgtg   2520

gaaaacaccc agctgcagaa cgagaagctg tacctgtact acctgcagaa tgggcgggat   2580

atgtacgtgg accaggaact ggacatcaac cggctgtccg actacgatgt ggaccatatc   2640

gtgcctcaga gctttctgaa ggacgactcc atcgacaaca aggtgctgac cagaagcgac   2700

aagaaccggg gcaagagcga caacgtgccc tccgaagagg tcgtgaagaa gatgaagaac   2760

tactggcggc agctgctgaa cgccaagctg attacccaga gaaagttcga caatctgacc   2820

aaggccgaga gaggcggcct gagcgaactg gataaggccg gcttcatcaa gagacagctg   2880

gtggaaaccc ggcagatcac aaagcacgtg gcacagatcc tggactcccg gatgaacact   2940

aagtacgacg agaatgacaa gctgatccgg gaagtgaaag tgatcaccct gaagtccaag   3000

ctggtgtccg atttccggaa ggatttccag ttttacaaag tgcgcgagat caacaactac   3060

caccacgccc acgacgccta cctgaacgcc gtcgtgggaa ccgccctgat caaaaagtac   3120

cctaagctgg aaagcgagtt cgtgtacggc gactacaagg tgtacgacgt gcggaagatg   3180

atcgccaaga gcgagcagga aatcggcaag gctaccgcca agtacttctt ctacagcaac   3240

atcatgaact ttttcaagac cgagattacc ctggccaacg gcgagatccg gaagcggcct   3300

ctgatcgaga caaacggcga aaccggggag atcgtgtggg ataagggccg ggattttgcc   3360

accgtgcgga aagtgctgag catgccccaa gtgaatatcg tgaaaaagac cgaggtgcag   3420

acaggcggct tcagcaaaga gtctatcctg cccaagagga acagcgataa gctgatcgcc   3480

agaaagaagg actgggaccc taagaagtac ggcggcttcg acagccccac cgtggcctat   3540

tctgtgctgg tggtggccaa agtggaaaag ggcaagtcca agaaactgaa gagtgtgaaa   3600

gagctgctgg ggatcaccat catggaaaga agcagcttcg agaagaatcc catcgacttt   3660

ctggaagcca agggctacaa agaagtgaaa aaggacctga tcatcaagct gcctaagtac   3720

tccctgttcg agctggaaaa cggccggaag agaatgctgg cctctgccgg cgaactgcag   3780

aagggaaacg aactggccct gccctccaaa tatgtgaact tcctgtacct ggccagccac   3840

tatgagaagc tgaagggctc ccccgaggat aatgagcaga aacagctgtt tgtggaacag   3900

cacaagcact acctggacga gatcatcgag cagatcagcg agttctccaa gagagtgatc   3960

ctggccgacg ctaatctgga caaagtgctg tccgcctaca acaagcaccg ggataagccc   4020

atcagagagc aggccgagaa tatcatccac ctgtttaccc tgaccaatct gggagcccct   4080

gccgccttca agtactttga caccaccatc gaccggaaga ggtacaccag caccaaagag   4140

gtgctggacg ccaccctgat ccaccagagc atcaccggcc tgtacgagac acggatcgac   4200

ctgtctcagc tgggaggcga caaaaggccg gcggccacga aaaaggccgg ccaggcaaaa   4260

aagaaaaagg aattc                                                    4275


<210>  40
<211>  22
<212>  DNA
<213>  Artificial

<220>
<223>  target sequence for miR122 (human)

<400>  40
caaacaccat tgtcacactc ca                                              22


<210>  41
<211>  22
<212>  DNA
<213>  Artificial

<220>
<223>  miR1 target sequence

<400>  41
atacatactt ctttacattc ca                                              22


<210>  42
<211>  21
<212>  DNA
<213>  Artificial

<220>
<223>  miR142-5p target sequence

<400>  42
agtagtgctt tctactttat g                                               21


<210>  43
<211>  23
<212>  DNA
<213>  Artificial

<220>
<223>  miR142-3p target sequence

<400>  43
tccataaagt aggaaacact aca                                             23


<210>  44
<211>  71
<212>  RNA
<213>  Homo sapiens

<400>  44
ugggaaacau acuucuuuau augcccauau ggaccugcua agcuauggaa uguaaagaag     60

uauguaucuc a                                                          71


<210>  45
<211>  86
<212>  RNA
<213>  Homo sapiens

<400>  45
ugcuucccga ggccacaugc uucuuuauau ccccauaugg auuacuuugc uauggaaugu     60

aaggaagugu gugguuucgg caagug                                          86


<210>  46
<211>  71
<212>  RNA
<213>  Homo sapiens

<400>  46
ugacgggcga gcuuuuggcc cggguuauac cugaugcuca cguauaagac gagcaaaaag     60

cuuguugguc a                                                          71


<210>  47
<211>  85
<212>  RNA
<213>  Homo sapiens

<400>  47
ccuuagcaga gcuguggagu gugacaaugg uguuuguguc uaaacuauca aacgccauua     60

ucacacuaaa uagcuacugc uaggc                                           85


<210>  48
<211>  87
<212>  RNA
<213>  Homo sapiens

<400>  48
gacagugcag ucacccauaa aguagaaagc acuacuaaca gcacuggagg guguaguguu     60

uccuacuuua uggaugagug uacugug                                         87


<210>  49
<211>  61
<212>  DNA
<213>  Artificial

<220>
<223>  upper sequence in Fig. 1B

<400>  49
aattagagac gccgttgatg ttgaagttta tataccgttg atgttgaagt cgtctctagc     60

t                                                                     61


<210>  50
<211>  61
<212>  DNA
<213>  Artificial

<220>
<223>  lower sequence in Fig. 1B

<400>  50
aattacaaac accattgtca cactccatta tatacaaaca ccattgtcac actccatagc     60

t                                                                     61


