                         SEQUENCE LISTING

<110>  CRISPR THERAPEUTICS AG et al.
 
<120>  COMPOSITIONS AND METHODS FOR EDITING BETA-GLOBIN FOR TREATMENT OF
        HEMAGLOBINOPATHIES

<130>  CRTN-115BPC

<140>  PCT/US2020/038203
<141>  2020-06-17

<150>  US 62/862,539
<151>  2019-06-17

<160>  122   

<170>  PatentIn version 3.5

<210>  1
<211>  114
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, sgRNA1


<220>
<221>  misc_feature
<222>  (1)..(30)
<223>  n is any nucleotide; n is present at least 17 and up to 30 times

<220>
<221>  misc_feature
<222>  (107)..(114)
<223>  u is present at least 1 time and up to 8 times

<400>  1
nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn guuuuagagc uagaaauagc aaguuaaaau       60

aaggcuaguc cguuaucaac uugaaaaagu ggcaccgagu cggugcuuuu uuuu            114


<210>  2
<211>  119
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, SpCas9 sgRNA


<220>
<221>  modified_base
<222>  (1)..(6)
<223>  every c and u is a 2' O-methyl phosphorothioate nucleotide

<220>
<221>  misc_feature
<222>  (2)..(2)
<223>  n is a phosphorothioate nucleotide

<220>
<221>  misc_feature
<222>  (4)..(4)
<223>  n is a phosphorothioate nucleotide

<220>
<221>  misc_feature
<222>  (6)..(6)
<223>  n is a phosphorothioate nucleotide

<220>
<221>  misc_feature
<222>  (7)..(36)
<223>  n is any nucleotide and repeats 17 times and up to 30 times

<220>
<221>  modified_base
<222>  (113)..(118)
<223>  every u is a 2' O-methyl phosphorothioate nucleotide

<220>
<221>  misc_feature
<222>  (114)..(114)
<223>  n is a phosphorothioate nucleotide

<220>
<221>  misc_feature
<222>  (116)..(116)
<223>  n is a phosphorothioate nucleotide

<220>
<221>  misc_feature
<222>  (118)..(118)
<223>  n is a phosphorothioate nucleotide

<400>  2
cnununnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnguuu uagagcuaga aauagcaagu       60

uaaaauaagg cuaguccguu aucaacuuga aaaaguggca ccgagucggu gcunununu       119


<210>  3
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, AAVS1 target sequence A

<400>  3
ggggccacta gggacaggat                                                   20


<210>  4
<211>  20
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, AAVS1 sgRNA spacer A

<400>  4
ggggccacua gggacaggau                                                   20


<210>  5
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, AAVS1 target sequence B

<400>  5
gccagtagcc agccccgtcc                                                   20


<210>  6
<211>  20
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, AAVS1 sgRNA spacer B

<400>  6
gccaguagcc agccccgucc                                                   20


<210>  7
<211>  18
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, BFP target sequence

<400>  7
tgaagcactg cacgccat                                                     18


<210>  8
<211>  18
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, BFP sgRNA spacer

<400>  8
ugaagcacug cacgccau                                                     18


<210>  9
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, GFP target sequence A

<400>  9
gctgaagcac tgcacgccgt                                                   20


<210>  10
<211>  20
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, GFP sgRNA spacer A

<400>  10
gcugaagcac ugcacgccgu                                                   20


<210>  11
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, GFP target sequence B

<400>  11
ctcgtgacca ccctgaccta                                                   20


<210>  12
<211>  20
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, GFP sgRNA spacer B

<400>  12
cucgugacca cccugaccua                                                   20


<210>  13
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, GSD1a target sequence

<400>  13
tctttggaca gcgtccatac                                                   20


<210>  14
<211>  20
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, GSD1a Ch32 gRNA spacer

<400>  14
ucuuuggaca gcguccauac                                                   20


<210>  15
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, HBB target sequence

<400>  15
cttgccccac agggcagtaa                                                   20


<210>  16
<211>  20
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, HBB RO2 sgRNA spacer

<400>  16
cuugccccac agggcaguaa                                                   20


<210>  17
<211>  106
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, HBB sgRNA


<220>
<221>  modified_base
<222>  (1)..(6)
<223>  every c and u is a 2' O-methyl phosphorothioate nucleotide

<220>
<221>  misc_feature
<222>  (2)..(2)
<223>  n is a phosphorothioate nucleotide

<220>
<221>  misc_feature
<222>  (4)..(4)
<223>  n is a phosphorothioate nucleotide

<220>
<221>  misc_feature
<222>  (6)..(6)
<223>  n is a phosphorothioate nucleotide

<220>
<221>  modified_base
<222>  (100)..(104)
<223>  every u is a 2' O-methyl phosphorothioate nucleotide

<220>
<221>  misc_feature
<222>  (101)..(101)
<223>  n is a phosphorothioate nucleotide

<220>
<221>  misc_feature
<222>  (103)..(103)
<223>  n is a phosphorothioate nucleotide

<220>
<221>  misc_feature
<222>  (105)..(105)
<223>  n is a phosphorothioate nucleotide

<400>  17
cnunungccc cacagggcag uaaguuuuag agcuagaaau agcaaguuaa aauaaggcua       60

guccguuauc aacuugaaaa aguggcaccg agucggugcu nununu                     106


<210>  18
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, CFTR target sequence

<400>  18
tctgtatcta tattcatcat                                                   20


<210>  19
<211>  20
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, CFTR sgRNA spacer

<400>  19
ucuguaucua uauucaucau                                                   20


<210>  20
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: gRNA-related, HBB Target Sequence

<400>  20
cttgccccac agggcagtaa cgg                                               23


<210>  21
<211>  127
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, ssODN1 (Ht-CR282)

<400>  21
gccacctacg gcaagctgac cctgaagttc atctgcacca ccggcaagct gcccgtgccc       60

tggcccaccc tcgtgaccac cctgacgtac ggcgtgcagt gcttcagccg ctaccccgac      120

cacatga                                                                127


<210>  22
<211>  127
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, ssODN2 (Hn-CR283)

<400>  22
tcatgtggtc ggggtagcgg ctgaagcact gcacgccgta cgtcagggtg gtcacgaggg       60

tgggccaggg cacgggcagc ttgccggtgg tgcagatgaa cttcagggtc agcttgccgt      120

aggtggc                                                                127


<210>  23
<211>  127
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, ssODN3 (Hn-39-88)

<400>  23
cgctcctgga cgtagccttc gggcatggcg gacttgaaga agtcgtgctg cttcatgtgg       60

tcggggtagc ggctgaagca ctgcacgccg tacgtcaggg tggtcacgag ggtgggccag      120

ggcacgg                                                                127


<210>  24
<211>  152
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, ssODN4 (Ht-91-61)

<400>  24
gccacctacg gcaagctgac cctgaagttc atctgcacca ccggcaagct gcccgtgccc       60

tggcccaccc tcgtgaccac cctgacgtac ggcgtgcagt gcttcagccg ctaccccgac      120

cacatgaagc agcacgactt cttcaagtcc gc                                    152


<210>  25
<211>  152
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, ssODN (Hn-91-61)

<400>  25
gcggacttga agaagtcgtg ctgcttcatg tggtcggggt agcggctgaa gcactgcacg       60

ccgtacgtca gggtggtcac gagggtgggc cagggcacgg gcagcttgcc ggtggtgcag      120

atgaacttca gggtcagctt gccgtaggtg gc                                    152


<210>  26
<211>  127
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, ssODN (Hn-91-36)

<400>  26
tcatgtggtc ggggtagcgg ctgaagcact gcacgccgta cgtcagggtg gtcacgaggg       60

tgggccaggg cacgggcagc ttgccggtgg tgcagatgaa cttcagggtc agcttgccgt      120

aggtggc                                                                127


<210>  27
<211>  152
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, ssODN (Ht-91-61)

<400>  27
gccacctacg gcaagctgac cctgaagttc atctgcacca ccggcaagct gcccgtgccc       60

tggcccaccc tcgtgaccac cctgacgtac ggcgtgcagt gcttcagccg ctaccccgac      120

cacatgaagc agcacgactt cttcaagtcc gc                                    152


<210>  28
<211>  127
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, ssODN (Ht-39-88)

<400>  28
cgctcctgga cgtagccttc gggcatggcg gacttgaaga agtcgtgctg cttcatgtgg       60

tcggggtagc ggctgaagca ctgcacgccg tacgtcaggg tggtcacgag ggtgggccag      120

ggcacgg                                                                127


<210>  29
<211>  127
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, ssODN 1067

<400>  29
gccacctacg gcaagctgac cctgaagttc atctgcacca ccggcaagct gcccgtgccc       60

tggcccaccc tcgtgaccac cctgagccac ggggtgcagt gcttcagccg ctaccccgac      120

cacatga                                                                127


<210>  30
<211>  127
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, ssODN 1068

<400>  30
tcatgtggtc ggggtagcgg ctgaagcact gcaccccgtg gctcagggtg gtcacgaggg       60

tgggccaggg cacgggcagc ttgccggtgg tgcagatgaa cttcagggtc agcttgccgt      120

aggtggc                                                                127


<210>  31
<211>  127
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, ssODN 1069

<400>  31
tcatctgcac caccggcaag ctgcccgtgc cctggcccac cctcgtgacc accctgagcc       60

acggggtgca gtgcttcagc cgctaccccg accacatgaa gcagcacgac ttcttcaagt      120

ccgccat                                                                127


<210>  32
<211>  127
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, ssODN 1070

<400>  32
atggcggact tgaagaagtc gtgctgcttc atgtggtcgg ggtagcggct gaagcactgc       60

accccgtggc tcagggtggt cacgagggtg ggccagggca cgggcagctt gccggtggtg      120

cagatga                                                                127


<210>  33
<211>  127
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, ssODN 1061

<400>  33
ctcctggacg tagccttcgg gcatggcgga cttgaagaag tcgtgctgct tcatgtggtc       60

ggggtagcgg ctgaagcact gcaccccgtg gctcagggtg gtcacgaggg tgggccaggg      120

cacgggc                                                                127


<210>  34
<211>  127
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, ssODN 1062

<400>  34
gcccgtgccc tggcccaccc tcgtgaccac cctgagccac ggggtgcagt gcttcagccg       60

ctaccccgac cacatgaagc agcacgactt cttcaagtcc gccatgcccg aaggctacgt      120

ccaggag                                                                127


<210>  35
<211>  127
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, ssODN 1063

<400>  35
gacttgaaga agtcgtgctg cttcatgtgg tcggggtagc ggctgaagca ctgcaccccg       60

tggctcaggg tggtcacgag ggtgggccag ggcacgggca gcttgccggt ggtgcagatg      120

aacttca                                                                127


<210>  36
<211>  127
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, ssODN 1064

<400>  36
tgaagttcat ctgcaccacc ggcaagctgc ccgtgccctg gcccaccctc gtgaccaccc       60

tgagccacgg ggtgcagtgc ttcagccgct accccgacca catgaagcag cacgacttct      120

tcaagtc                                                                127


<210>  37
<211>  50
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, 50-0 dsDNA

<400>  37
cccagaaact tgttctgttt ttccatagga ttctctttgg acagtgccct                  50


<210>  38
<211>  150
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, 150-0 dsDNA

<400>  38
agggcactgt ccaaagagaa tcctatggaa aaacagaaca agtttctggg gttactgaat       60

gaatgctttt gcccaaagcc tacaccttca agaagagtgt agcctgagaa ggatttcaca      120

tgttgcctct agaagggaga actgggtggc                                       150


<210>  39
<211>  142
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, 93-50 ssODN

<400>  39
tcttgaaggt gtaggctttg ggcaaaagca ttcattcagt aaccccagaa acttgttctg       60

tttttccata ggattctctt tggacagtgc ccttactggt gggtcctgga tactgactac      120

tacagcaaca cttccgtgcc ct                                               142


<210>  40
<211>  125
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, 25-100 ssODN

<400>  40
taggattctc tttggacagt gcccttactg gtgggtcctg gatactgact actacagcaa       60

cacttccgtg cccctgataa agcagttccc tgtaacctgt gagactggac caggtaagcg      120

tccca                                                                  125


<210>  41
<211>  125
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, H3-95-30 ssODN

<400>  41
taagcacagt ggaagaattt cattctgttc tcagttttcc tggattatgc ctggcaccat       60

taaagaaaat atcataagct ttggtgtttg ctatgatgaa tatagataca gaagcgtcat      120

caaag                                                                  125


<210>  42
<211>  125
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, N1-95-30 ssODN

<400>  42
aattaagcac agtggaagaa tttcattctg ttctcagttt tcctggatta tgcctggcac       60

cattaaagaa aatatcatct ttggtgtttg ctagcatgat gaatatagat acagaagcgt      120

catca                                                                  125


<210>  43
<211>  1000
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA , AAVS1 locus LHA (used for BFP donor)

<400>  43
ccccagctct tctctgttca gccctaagaa tcctggctcc agcccctcct actctagccc       60

ccaaccccct agccactaag gcaattgggg tgcaggaatg ggggcagggt accagcctca      120

ccaagtggtt gataaaccca cgtggggtac cctaagaact tgggaacagc cacagcaggg      180

gggcgatgct tggggacctg cctggagaag gatgcaggac gagaaacaca gccccaggtg      240

gagaaactgg ccgggaatca agagtcaccc agagacagtg accaaccatc cctgttttcc      300

taggactgag ggtttcagtg ctaaaactag gctgtcctgg gcaaacagca taagctggtc      360

accccacacc cagacctgac ccaaacccag ctcccctgct tcttggccac gtaacctgag      420

aagggaatcc ctcctctctg aaccccagcc caccccaatg ctccaggcct cctgggatac      480

cccgaagagt gagtttgcca agcagtcacc ccacagttgg aggagaatcc acccaaaagg      540

cagcctggta gacagggctg gggtggcctc tcgtggggtc caggccaagt aggtggcctg      600

gggcctctgg gggatgcagg ggaaggggga tgcaggggaa cggggatgca ggggaacggg      660

gctcagtctg aagagcagag ccaggaaccc ctgtagggaa ggggcaggag agccaggggc      720

atgagatggt ggacgaggaa gggggacagg gaagcctgag cgcctctcct gggcttgcca      780

aggactcaaa cccagaagcc cagagcaggg ccttagggaa gcgggaccct gctctgggcg      840

gaggaatatg tcccagatag cactggggac tctttaagga aagaaggatg gagaaagaga      900

aagggagtag aggcggccac gacctggtga acacctagga cgcaccattc tcacaaaggg      960

agttttccac acggacaccc ccctcctcac cacagccctg                           1000


<210>  44
<211>  717
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, BFP locus donor

<400>  44
atggtgagca agggcgagga gctgttcacc ggggtggtgc ccatcctggt cgagctggac       60

ggcgacgtaa acggccacaa gttcagcgtg tccggcgagg gcgagggcga tgccacctac      120

ggcaagctga ccctgaagtt catctgcacc accggcaagc tgcccgtgcc ctggcccacc      180

ctcgtgacca ccctgaccca tggcgtgcag tgcttcagcc gctaccccga ccacatgaag      240

cagcacgact tcttcaagtc cgccatgccc gaaggctacg tccaggagcg caccatcttc      300

ttcaaggacg acggcaacta caagacccgc gccgaggtga agttcgaggg cgacaccctg      360

gtgaaccgca tcgagctgaa gggcatcgac ttcaaggagg acggcaacat cctggggcac      420

aagctggagt acaactacaa cagccacaac gtctatatca tggccgacaa gcagaagaac      480

ggcatcaagg tgaacttcaa gatccgccac aacatcgagg acggcagcgt gcagctcgcc      540

gaccactacc agcagaacac ccccatcggc gacggccccg tgctgctgcc cgacaaccac      600

tacctgagca cccagtccaa gctgagcaaa gaccccaacg agaagcgcga tcacatggtc      660

ctgctggagt tcgtgaccgc cgccgggatc actctcggca tggacgagct gtacaag         717


<210>  45
<211>  1000
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, AAVS1 locus RHA (used for BFP donor)

<400>  45
actgtggggt ggaggggaca gataaaagta cccagaacca gagccacatt aaccggccct       60

gggaatataa ggtggtccca gctcggggac acaggatccc tggaggcagc aaacatgctg      120

tcctgaagtg gacatagggg cccgggttgg aggaagaaga ctagctgagc tctcggaccc      180

ctggaagatg ccatgacagg gggctggaag agctagcaca gactagagag gtaagggggg      240

taggggagct gcccaaatga aaggagtgag aggtgacccg aatccacagg agaacggggt      300

gtccaggcaa agaaagcaag aggatggaga ggtggctaaa gccagggaga cggggtactt      360

tggggttgtc cagaaaaacg gtgatgatgc aggcctacaa gaaggggagg cgggacgcaa      420

gggagacatc cgtcggagaa ggccatccta agaaacgaga gatggcacag gccccagaag      480

gagaaggaaa agggaaccca gcgagtgaag acggcatggg gttgggtgag ggaggagaga      540

tgcccggaga ggacccagac acggggagga tccgctcaga ggacatcacg tggtgcagcg      600

ccgagaagga agtgctccgg aaagagcatc cttgggcagc aacacagcag agagcaaggg      660

gaagagggag tggaggaaga cggaacctga aggaggcggc agggaaggat ctgggccagc      720

cgtagaggtg acccaggcca caagctgcag acagaaagcg gcacaggccc aggggagaga      780

atgcaggtca gagaaagcag gacctgcctg ggaaggggaa acagtgggcc agaggcggcg      840

cagaagccag tagagctcaa agtggtccgg actcaggaga gagacggcag cgttagaggg      900

cagagttccg gcggcacagc aagggcactc gggggcgaga ggagggcagc gcaaagtgac      960

aatggccagg gccaggcaga tagaccagac tgagctatgg                           1000


<210>  46
<211>  1000
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, AAVS1 locus LHA (used for GFP donor)

<400>  46
ccccagctct tctctgttca gccctaagaa tcctggctcc agcccctcct actctagccc       60

ccaaccccct agccactaag gcaattgggg tgcaggaatg ggggcagggt accagcctca      120

ccaagtggtt gataaaccca cgtggggtac cctaagaact tgggaacagc cacagcaggg      180

gggcgatgct tggggacctg cctggagaag gatgcaggac gagaaacaca gccccaggtg      240

gagaaactgg ccgggaatca agagtcaccc agagacagtg accaaccatc cctgttttcc      300

taggactgag ggtttcagtg ctaaaactag gctgtcctgg gcaaacagca taagctggtc      360

accccacacc cagacctgac ccaaacccag ctcccctgct tcttggccac gtaacctgag      420

aagggaatcc ctcctctctg aaccccagcc caccccaatg ctccaggcct cctgggatac      480

cccgaagagt gagtttgcca agcagtcacc ccacagttgg aggagaatcc acccaaaagg      540

cagcctggta gacagggctg gggtggcctc tcgtggggtc caggccaagt aggtggcctg      600

gggcctctgg gggatgcagg ggaaggggga tgcaggggaa cggggatgca ggggaacggg      660

gctcagtctg aagagcagag ccaggaaccc ctgtagggaa ggggcaggag agccaggggc      720

atgagatggt ggacgaggaa gggggacagg gaagcctgag cgcctctcct gggcttgcca      780

aggactcaaa cccagaagcc cagagcaggg ccttagggaa gcgggaccct gctctgggcg      840

gaggaatatg tcccagatag cactggggac tctttaagga aagaaggatg gagaaagaga      900

aagggagtag aggcggccac gacctggtga acacctagga cgcaccattc tcacaaaggg      960

agttttccac acggacaccc ccctcctcac cacagccctg                           1000


<210>  47
<211>  720
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, GFP donor to AAVS1 locus

<400>  47
atggtgagca agggcgagga gctgttcacc ggggtggtgc ccatcctggt cgagctggac       60

ggcgacgtaa acggccacaa gttcagcgtg tccggcgagg gcgagggcga tgccacctac      120

ggcaagctga ccctgaagtt catctgcacc accggcaagc tgcccgtgcc ctggcccacc      180

ctcgtgacca ccctgaccta cggcgtgcag tgcttcagcc gctaccccga ccacatgaag      240

cagcacgact tcttcaagtc cgccatgccc gaaggctacg tccaggagcg caccatcttc      300

ttcaaggacg acggcaacta caagacccgc gccgaggtga agttcgaggg cgacaccctg      360

gtgaaccgca tcgagctgaa gggcatcgac ttcaaggagg acggcaacat cctggggcac      420

aagctggagt acaactacaa cagccacaac gtctatatca tggccgacaa gcagaagaac      480

ggcatcaagg tgaacttcaa gatccgccac aacatcgagg acggcagcgt gcagctcgcc      540

gaccactacc agcagaacac ccccatcggc gacggccccg tgctgctgcc cgacaaccac      600

tacctgagca cccagtccgc cctgagcaaa gaccccaacg agaagcgcga tcacatggtc      660

ctgctggagt tcgtgaccgc cgccgggatc actctcggca tggacgagct gtacaagtaa      720


<210>  48
<211>  1000
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, AAVS1 locus RHA (used for GFP donor)

<400>  48
actgtggggt ggaggggaca gataaaagta cccagaacca gagccacatt aaccggccct       60

gggaatataa ggtggtccca gctcggggac acaggatccc tggaggcagc aaacatgctg      120

tcctgaagtg gacatagggg cccgggttgg aggaagaaga ctagctgagc tctcggaccc      180

ctggaagatg ccatgacagg gggctggaag agctagcaca gactagagag gtaagggggg      240

taggggagct gcccaaatga aaggagtgag aggtgacccg aatccacagg agaacggggt      300

gtccaggcaa agaaagcaag aggatggaga ggtggctaaa gccagggaga cggggtactt      360

tggggttgtc cagaaaaacg gtgatgatgc aggcctacaa gaaggggagg cgggacgcaa      420

gggagacatc cgtcggagaa ggccatccta agaaacgaga gatggcacag gccccagaag      480

gagaaggaaa agggaaccca gcgagtgaag acggcatggg gttgggtgag ggaggagaga      540

tgcccggaga ggacccagac acggggagga tccgctcaga ggacatcacg tggtgcagcg      600

ccgagaagga agtgctccgg aaagagcatc cttgggcagc aacacagcag agagcaaggg      660

gaagagggag tggaggaaga cggaacctga aggaggcggc agggaaggat ctgggccagc      720

cgtagaggtg acccaggcca caagctgcag acagaaagcg gcacaggccc aggggagaga      780

atgcaggtca gagaaagcag gacctgcctg ggaaggggaa acagtgggcc agaggcggcg      840

cagaagccag tagagctcaa agtggtccgg actcaggaga gagacggcag cgttagaggg      900

cagagttccg gcggcacagc aagggcactc gggggcgaga ggagggcagc gcaaagtgac      960

aatggccagg gccaggcaga tagaccagac tgagctatgg                           1000


<210>  49
<211>  2189
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, HBB locus LHA (used for E7 to E7V AAV.304)

<400>  49
cttgctttga caattttggt ctttcagaat actataaata taacctatat tataatttca       60

taaagtctgt gcattttctt tgacccagga tatttgcaaa agacatattc aaacttccgc      120

agaacacttt atttcacata tacatgcctc ttatatcagg gatgtgaaac agggtcttga      180

aaactgtcta aatctaaaac aatgctaatg caggtttaaa tttaataaaa taaaatccaa      240

aatctaacag ccaagtcaaa tctgcatgtt ttaacattta aaatatttta aagacgtctt      300

ttcccaggat tcaacatgtg aaatcttttc tcagggatac acgtgtgcct agatcctcat      360

tgctttagtt ttttacagag gaatgaatat aaaaagaaaa tacttaaatt ttatccctct      420

tacctctata atcatacata ggcataattt tttaacctag gctccagata gccatagaag      480

aaccaaacac tttctgcgtg tgtgagaata atcagagtga gattttttca caagtacctg      540

atgagggttg agacaggtag aaaaagtgag agatctctat ttatttagca ataatagaga      600

aagcatttaa gagaataaag caatggaaat aagaaatttg taaatttcct tctgataact      660

agaaatagag gatccagttt cttttggtta acctaaattt tatttcattt tattgtttta      720

ttttatttta ttttatttta ttttgtgtaa tcgtagtttc agagtgttag agctgaaagg      780

aagaagtagg agaaacatgc aaagtaaaag tataacactt tccttactaa accgacatgg      840

gtttccaggt aggggcagga ttcaggatga ctgacagggc ccttagggaa cactgagacc      900

ctacgctgac ctcataaatg cttgctacct ttgctgtttt aattacatct tttaatagca      960

ggaagcagaa ctctgcactt caaaagtttt tcctcacctg aggagttaat ttagtacaag     1020

gggaaaaagt acagggggat gggagaaagg cgatcacgtt gggaagctat agagaaagaa     1080

gagtaaattt tagtaaagga ggtttaaaca aacaaaatat aaagagaaat aggaacttga     1140

atcaaggaaa tgattttaaa acgcagtatt cttagtggac tagaggaaaa aaataatctg     1200

agccaagtag aagacctttt cccctcctac ccctactttc taagtcacag aggctttttg     1260

ttcccccaga cactcttgca gattagtcca ggcagaaaca gttagatgtc cccagttaac     1320

ctcctatttg acaccactga ttaccccatt gatagtcaca ctttgggttg taagtgactt     1380

tttatttatt tgtatttttg actgcattaa gaggtctcta gttttttatc tcttgtttcc     1440

caaaacctaa taagtaacta atgcacagag cacattgatt tgtatttatt ctatttttag     1500

acataattta ttagcatgca tgagcaaatt aagaaaaaca acaacaaatg aatgcatata     1560

tatgtatatg tatgtgtgta tatatacaca catatatata tatatttttt cttttcttac     1620

cagaaggttt taatccaaat aaggagaaga tatgcttaga accgaggtag agttttcatc     1680

cattctgtcc tgtaagtatt ttgcatattc tggagacgca ggaagagatc catctacata     1740

tcccaaagct gaattatggt agacaaaact cttccacttt tagtgcatca acttcttatt     1800

tgtgtaataa gaaaattggg aaaacgatct tcaatatgct taccaagctg tgattccaaa     1860

tattacgtaa atacacttgc aaaggaggat gtttttagta gcaatttgta ctgatggtat     1920

ggggccaaga gatatatctt agagggaggg ctgagggttt gaagtccaac tcctaagcca     1980

gtgccagaag agccaaggac aggtacggct gtcatcactt agacctcacc ctgtggagcc     2040

acaccctagg gttggccaat ctactcccag gagcagggag ggcaggagcc agggctgggc     2100

ataaaagtca gggcagagcc atctattgct tacatttgct tctgacacaa ctgtgttcac     2160

tagcaacctc aaacagacac catggtgca                                       2189


<210>  50
<211>  46
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, E7 to E7V AAV.304

<400>  50
tctgactcct gtcgagaagt ctgcagtcac tgctctatgg gggaaa                      46


<210>  51
<211>  2200
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, HBB locus RHA (used for E7 to E7V AAV.304)

<400>  51
gtgaacgtgg atgaagttgg tggtgaggcc ctgggcaggt tggtatcaag gttacaagac       60

aggtttaagg agaccaatag aaactgggca tgtggagaca gagaagactc ttgggtttct      120

gataggcact gactctctct gcctattggt ctattttccc acccttaggc tgctggtggt      180

ctacccttgg acccagaggt tctttgagtc ctttggggat ctgtccactc ctgatgctgt      240

tatgggcaac cctaaggtga aggctcatgg caagaaagtg ctcggtgcct ttagtgatgg      300

cctggctcac ctggacaacc tcaagggcac ctttgccaca ctgagtgagc tgcactgtga      360

caagctgcac gtggatcctg agaacttcag ggtgagtcta tgggacgctt gatgttttct      420

ttccccttct tttctatggt taagttcatg tcataggaag gggataagta acagggtaca      480

gtttagaatg ggaaacagac gaatgattgc atcagtgtgg aagtctcagg atcgttttag      540

tttcttttat ttgctgttca taacaattgt tttcttttgt ttaattcttg ctttcttttt      600

ttttcttctc cgcaattttt actattatac ttaatgcctt aacattgtgt ataacaaaag      660

gaaatatctc tgagatacat taagtaactt aaaaaaaaac tttacacagt ctgcctagta      720

cattactatt tggaatatat gtgtgcttat ttgcatattc ataatctccc tactttattt      780

tcttttattt ttaattgata cataatcatt atacatattt atgggttaaa gtgtaatgtt      840

ttaatatgtg tacacatatt gaccaaatca gggtaatttt gcatttgtaa ttttaaaaaa      900

tgctttcttc ttttaatata cttttttgtt tatcttattt ctaatacttt ccctaatctc      960

tttctttcag ggcaataatg atacaatgta tcatgcctct ttgcaccatt ctaaagaata     1020

acagtgataa tttctgggtt aaggcaatag caatatctct gcatataaat atttctgcat     1080

ataaattgta actgatgtaa gaggtttcat attgctaata gcagctacaa tccagctacc     1140

attctgcttt tattttatgg ttgggataag gctggattat tctgagtcca agctaggccc     1200

ttttgctaat catgttcata cctcttatct tcctcccaca gctcctgggc aacgtgctgg     1260

tctgtgtgct ggcccatcac tttggcaaag aattcacccc accagtgcag gctgcctatc     1320

agaaagtggt ggctggtgtg gctaatgccc tggcccacaa gtatcactaa gctcgctttc     1380

ttgctgtcca atttctatta aaggttcctt tgttccctaa gtccaactac taaactgggg     1440

gatattatga agggccttga gcatctggat tctgcctaat aaaaaacatt tattttcatt     1500

gcaatgatgt atttaaatta tttctgaata ttttactaaa aagggaatgt gggaggtcag     1560

tgcatttaaa acataaagaa atgaagagct agttcaaacc ttgggaaaat acactatatc     1620

ttaaactcca tgaaagaagg tgaggctgca aacagctaat gcacattggc aacagcccct     1680

gatgcatatg ccttattcat ccctcagaaa aggattcaag tagaggcttg atttggaggt     1740

taaagttttg ctatgctgta ttttacatta cttattgttt tagctgtcct catgaatgtc     1800

ttttcactac ccatttgctt atcctgcatc tctcagcctt gactccactc agttctcttg     1860

cttagagata ccacctttcc cctgaagtgt tccttccatg ttttacggcg agatggtttc     1920

tcctcgcctg gccactcagc cttagttgtc tctgttgtct tatagaggtc tacttgaaga     1980

aggaaaaaca ggggtcatgg tttgactgtc ctgtgagccc ttcttccctg cctcccccac     2040

tcacagtgac ccggaatctg cagtgctagt ctcccggaac tatcactctt tcacagtctg     2100

ctttggaagg actgggctta gtatgaaaag ttaggactga gaagaatttg aaaggcggct     2160

ttttgtagct tgatattcac tactgtctta ttaccctgtc                           2200


<210>  52
<211>  2189
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, HBB locus LHA (used for E7 to E7V AAV.307)

<400>  52
cttgctttga caattttggt ctttcagaat actataaata taacctatat tataatttca       60

taaagtctgt gcattttctt tgacccagga tatttgcaaa agacatattc aaacttccgc      120

agaacacttt atttcacata tacatgcctc ttatatcagg gatgtgaaac agggtcttga      180

aaactgtcta aatctaaaac aatgctaatg caggtttaaa tttaataaaa taaaatccaa      240

aatctaacag ccaagtcaaa tctgcatgtt ttaacattta aaatatttta aagacgtctt      300

ttcccaggat tcaacatgtg aaatcttttc tcagggatac acgtgtgcct agatcctcat      360

tgctttagtt ttttacagag gaatgaatat aaaaagaaaa tacttaaatt ttatccctct      420

tacctctata atcatacata ggcataattt tttaacctag gctccagata gccatagaag      480

aaccaaacac tttctgcgtg tgtgagaata atcagagtga gattttttca caagtacctg      540

atgagggttg agacaggtag aaaaagtgag agatctctat ttatttagca ataatagaga      600

aagcatttaa gagaataaag caatggaaat aagaaatttg taaatttcct tctgataact      660

agaaatagag gatccagttt cttttggtta acctaaattt tatttcattt tattgtttta      720

ttttatttta ttttatttta ttttgtgtaa tcgtagtttc agagtgttag agctgaaagg      780

aagaagtagg agaaacatgc aaagtaaaag tataacactt tccttactaa accgacatgg      840

gtttccaggt aggggcagga ttcaggatga ctgacagggc ccttagggaa cactgagacc      900

ctacgctgac ctcataaatg cttgctacct ttgctgtttt aattacatct tttaatagca      960

ggaagcagaa ctctgcactt caaaagtttt tcctcacctg aggagttaat ttagtacaag     1020

gggaaaaagt acagggggat gggagaaagg cgatcacgtt gggaagctat agagaaagaa     1080

gagtaaattt tagtaaagga ggtttaaaca aacaaaatat aaagagaaat aggaacttga     1140

atcaaggaaa tgattttaaa acgcagtatt cttagtggac tagaggaaaa aaataatctg     1200

agccaagtag aagacctttt cccctcctac ccctactttc taagtcacag aggctttttg     1260

ttcccccaga cactcttgca gattagtcca ggcagaaaca gttagatgtc cccagttaac     1320

ctcctatttg acaccactga ttaccccatt gatagtcaca ctttgggttg taagtgactt     1380

tttatttatt tgtatttttg actgcattaa gaggtctcta gttttttatc tcttgtttcc     1440

caaaacctaa taagtaacta atgcacagag cacattgatt tgtatttatt ctatttttag     1500

acataattta ttagcatgca tgagcaaatt aagaaaaaca acaacaaatg aatgcatata     1560

tatgtatatg tatgtgtgta tatatacaca catatatata tatatttttt cttttcttac     1620

cagaaggttt taatccaaat aaggagaaga tatgcttaga accgaggtag agttttcatc     1680

cattctgtcc tgtaagtatt ttgcatattc tggagacgca ggaagagatc catctacata     1740

tcccaaagct gaattatggt agacaaaact cttccacttt tagtgcatca acttcttatt     1800

tgtgtaataa gaaaattggg aaaacgatct tcaatatgct taccaagctg tgattccaaa     1860

tattacgtaa atacacttgc aaaggaggat gtttttagta gcaatttgta ctgatggtat     1920

ggggccaaga gatatatctt agagggaggg ctgagggttt gaagtccaac tcctaagcca     1980

gtgccagaag agccaaggac aggtacggct gtcatcactt agacctcacc ctgtggagcc     2040

acaccctagg gttggccaat ctactcccag gagcagggag ggcaggagcc agggctgggc     2100

ataaaagtca gggcagagcc atctattgct tacatttgct tctgacacaa ctgtgttcac     2160

tagcaacctc aaacagacac catggtgca                                       2189


<210>  53
<211>  46
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, E7 to E7V AAV.307

<400>  53
tctgactcct gtcgaaaaat ccgctgtcac cgccctctgg ggcaag                      46


<210>  54
<211>  2200
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, HBB locus RHA (used for E7 to E7V AAV.307)

<400>  54
gtgaacgtgg atgaagttgg tggtgaggcc ctgggcaggt tggtatcaag gttacaagac       60

aggtttaagg agaccaatag aaactgggca tgtggagaca gagaagactc ttgggtttct      120

gataggcact gactctctct gcctattggt ctattttccc acccttaggc tgctggtggt      180

ctacccttgg acccagaggt tctttgagtc ctttggggat ctgtccactc ctgatgctgt      240

tatgggcaac cctaaggtga aggctcatgg caagaaagtg ctcggtgcct ttagtgatgg      300

cctggctcac ctggacaacc tcaagggcac ctttgccaca ctgagtgagc tgcactgtga      360

caagctgcac gtggatcctg agaacttcag ggtgagtcta tgggacgctt gatgttttct      420

ttccccttct tttctatggt taagttcatg tcataggaag gggataagta acagggtaca      480

gtttagaatg ggaaacagac gaatgattgc atcagtgtgg aagtctcagg atcgttttag      540

tttcttttat ttgctgttca taacaattgt tttcttttgt ttaattcttg ctttcttttt      600

ttttcttctc cgcaattttt actattatac ttaatgcctt aacattgtgt ataacaaaag      660

gaaatatctc tgagatacat taagtaactt aaaaaaaaac tttacacagt ctgcctagta      720

cattactatt tggaatatat gtgtgcttat ttgcatattc ataatctccc tactttattt      780

tcttttattt ttaattgata cataatcatt atacatattt atgggttaaa gtgtaatgtt      840

ttaatatgtg tacacatatt gaccaaatca gggtaatttt gcatttgtaa ttttaaaaaa      900

tgctttcttc ttttaatata cttttttgtt tatcttattt ctaatacttt ccctaatctc      960

tttctttcag ggcaataatg atacaatgta tcatgcctct ttgcaccatt ctaaagaata     1020

acagtgataa tttctgggtt aaggcaatag caatatctct gcatataaat atttctgcat     1080

ataaattgta actgatgtaa gaggtttcat attgctaata gcagctacaa tccagctacc     1140

attctgcttt tattttatgg ttgggataag gctggattat tctgagtcca agctaggccc     1200

ttttgctaat catgttcata cctcttatct tcctcccaca gctcctgggc aacgtgctgg     1260

tctgtgtgct ggcccatcac tttggcaaag aattcacccc accagtgcag gctgcctatc     1320

agaaagtggt ggctggtgtg gctaatgccc tggcccacaa gtatcactaa gctcgctttc     1380

ttgctgtcca atttctatta aaggttcctt tgttccctaa gtccaactac taaactgggg     1440

gatattatga agggccttga gcatctggat tctgcctaat aaaaaacatt tattttcatt     1500

gcaatgatgt atttaaatta tttctgaata ttttactaaa aagggaatgt gggaggtcag     1560

tgcatttaaa acataaagaa atgaagagct agttcaaacc ttgggaaaat acactatatc     1620

ttaaactcca tgaaagaagg tgaggctgca aacagctaat gcacattggc aacagcccct     1680

gatgcatatg ccttattcat ccctcagaaa aggattcaag tagaggcttg atttggaggt     1740

taaagttttg ctatgctgta ttttacatta cttattgttt tagctgtcct catgaatgtc     1800

ttttcactac ccatttgctt atcctgcatc tctcagcctt gactccactc agttctcttg     1860

cttagagata ccacctttcc cctgaagtgt tccttccatg ttttacggcg agatggtttc     1920

tcctcgcctg gccactcagc cttagttgtc tctgttgtct tatagaggtc tacttgaaga     1980

aggaaaaaca ggggtcatgg tttgactgtc ctgtgagccc ttcttccctg cctcccccac     2040

tcacagtgac ccggaatctg cagtgctagt ctcccggaac tatcactctt tcacagtctg     2100

ctttggaagg actgggctta gtatgaaaag ttaggactga gaagaatttg aaaggcggct     2160

ttttgtagct tgatattcac tactgtctta ttaccctgtc                           2200


<210>  55
<211>  803
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, HBB locus LHA (used for GFP AAV)

<400>  55
gactgcatta agaggtctct agttttttac ctcttgtttc ccaaaaccta ataagtaact       60

aatgcacaga gcacattgat ttgtatttat tctattttta gacataattt attagcatgc      120

atgagcaaat taagaaaaac aacaacaaat gaatgcatat atatgtatat gtatgtgtgt      180

acatatacac atatatatat attttttttc ttttcttacc agaaggtttt aatccaaata      240

aggagaagat atgcttagaa ctgaggtaga gttttcatcc attctgtcct gtaagtattt      300

tgcatattct ggagacgcag gaagagatcc atctacatat cccaaagctg aattatggta      360

gacaaaactc ttccactttt agtgcatcaa tttcttattt gtgtaataag aaaattggga      420

aaacgatctt caatatgctt accaagctgt gattccaaat attacgtaaa tacacttgca      480

aaggaggatg tttttagtag caatttgtac tgatggtatg gggccaagag atatatctta      540

gagggagggc tgagggtttg aagtccaact cctaagccag tgccagaaga gccaaggaca      600

ggtacggctg tcatcactta gacctcaccc tgtggagcca caccctaggg ttggccaatc      660

tactcccagg agcagggagg gcaggagcca gggctgggca taaaagtcag ggcagagcca      720

tctattgctt acatttgctt ctgacacaac tgtgttcact agcaacctca aacagacacc      780

atggtgcatc tgactcctga gga                                              803


<210>  56
<211>  720
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, GFP

<400>  56
atggtgagca agggcgagga gctgttcacc ggggtggtgc ccatcctggt cgagctggac       60

ggcgacgtaa acggccacaa gttcagcgtg tccggcgagg gcgagggcga tgccacctac      120

ggcaagctga ccctgaagtt catctgcacc accggcaagc tgcccgtgcc ctggcccacc      180

ctcgtgacca ccctgaccta cggcgtgcag tgcttcagcc gctaccccga ccacatgaag      240

cagcacgact tcttcaagtc cgccatgccc gaaggctacg tccaggagcg caccatcttc      300

ttcaaggacg acggcaacta caagacccgc gccgaggtga agttcgaggg cgacaccctg      360

gtgaaccgca tcgagctgaa gggcatcgac ttcaaggagg acggcaacat cctggggcac      420

aagctggagt acaactacaa cagccacaac gtctatatca tggccgacaa gcagaagaac      480

ggcatcaagg tgaacttcaa gatccgccac aacatcgagg acggcagcgt gcagctcgcc      540

gaccactacc agcagaacac ccccatcggc gacggccccg tgctgctgcc cgacaaccac      600

tacctgagca cccagtccgc cctgagcaaa gaccccaacg agaagcgcga tcacatggtc      660

ctgctggagt tcgtgaccgc cgccgggatc actctcggca tggacgagct gtacaagtaa      720


<210>  57
<211>  920
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, HBB locus RHA (used for GFP AAV)

<400>  57
ctgccctgtg gggcaaggtg aacgtggatg aagttggtgg tgaggccctg ggcaggttgg       60

tatcaaggtt acaagacagg tttaaggaga ccaatagaaa ctgggcatgt ggagacagag      120

aagactcttg ggtttctgat aggcactgac tctctctgcc tattggtcta ttttcccacc      180

cttaggctgc tggtggtcta cccttggacc cagaggttct ttgagtcctt tggggatctg      240

tccactcctg atgctgttat gggcaaccct aaggtgaagg ctcatggcaa gaaagtgctc      300

ggtgccttta gtgatggcct ggctcacctg gacaacctca agggcacctt tgccacactg      360

agtgagctgc actgtgacaa gctgcacgtg gatcctgaga acttcagggt gagtctatgg      420

gacgcttgat gttttctttc cccttctttt ctatggttaa gttcatgtca taggaagggg      480

ataagtaaca gggtacagtt tagaatggga aacagacgaa tgattgcatc agtgtggaag      540

tctcaggatc gttttagttt cttttatttg ctgttcataa caattgtttt cttttgttta      600

attcttgctt tctttttttt tcttctccgc aatttttact attatactta atgccttaac      660

attgtgtata acaaaaggaa atatctctga gatacattaa gtaacttaaa aaaaaacttt      720

acacagtctg cctagtacat tactatttgg aatatatgtg tgcttatttg catattcata      780

atctccctac tttattttct tttattttta attgatacat aatcattata catatttatg      840

ggttaaagtg taatgtttta atatgtgtac acatattgac caaatcaggg taattttgca      900

tttgtaattt taaaaaatgc                                                  920


<210>  58
<211>  451
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: MND promoter

<400>  58
ggccgccagt gtgatggata tctgcagaat tcgcccttat ggggatccga acagagagac       60

agcagaatat gggccaaaca ggatatctgt ggtaagcagt tcctgccccg gctcagggcc      120

aagaacagtt ggaacagcag aatatgggcc aaacaggata tctgtggtaa gcagttcctg      180

ccccggctca gggccaagaa cagatggtcc ccagatgcgg tcccgccctc agcagtttct      240

agagaaccat cagatgtttc cagggtgccc caaggacctg aaatgaccct gtgccttatt      300

tgaactaacc aatcagttcg cttctcgctt ctgttcgcgc gcttctgctc cccgagctct      360

atataagcag agctcgttta gtgaaccgtc agatcgcctg gagacgccat ccacgctgtt      420

ttgacctcca tagaagacac cgactctaga g                                     451


<210>  59
<211>  1178
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: EF1 promoter

<400>  59
ggctccggtg cccgtcagtg ggcagagcgc acatcgccca cagtccccga gaagttgggg       60

ggaggggtcg gcaattgaac cggtgcctag agaaggtggc gcggggtaaa ctgggaaagt      120

gatgtcgtgt actggctccg cctttttccc gagggtgggg gagaaccgta tataagtgca      180

gtagtcgccg tgaacgttct ttttcgcaac gggtttgccg ccagaacaca ggtaagtgcc      240

gtgtgtggtt cccgcgggcc tggcctcttt acgggttatg gcccttgcgt gccttgaatt      300

acttccactg gctgcagtac gtgattcttg atcccgagct tcgggttgga agtgggtggg      360

agagttcgag gccttgcgct taaggagccc cttcgcctcg tgcttgagtt gaggcctggc      420

ctgggcgctg gggccgccgc gtgcgaatct ggtggcacct tcgcgcctgt ctcgctgctt      480

tcgataagtc tctagccatt taaaattttt gatgacctgc tgcgacgctt tttttctggc      540

aagatagtct tgtaaatgcg ggccaagatc tgcacactgg tatttcggtt tttggggccg      600

cgggcggcga cggggcccgt gcgtcccagc gcacatgttc ggcgaggcgg ggcctgcgag      660

cgcggccacc gagaatcgga cgggggtagt ctcaagctgg ccggcctgct ctggtgcctg      720

gcctcgcgcc gccgtgtatc gccccgccct gggcggcaag gctggcccgg tcggcaccag      780

ttgcgtgagc ggaaagatgg ccgcttcccg gccctgctgc agggagctca aaatggagga      840

cgcggcgctc gggagagcgg gcgggtgagt cacccacaca aaggaaaagg gcctttccgt      900

cctcagccgt cgcttcatgt gactccacgg agtaccgggc gccgtccagg cacctcgatt      960

agttctcgag cttttggagt acgtcgtctt taggttgggg ggaggggttt tatgcgatgg     1020

agtttcccca cactgagtgg gtggagactg aagttaggcc agcttggcac ttgatgtaat     1080

tctccttgga atttgccctt tttgagtttg gatcttggtt cattctcaag cctcagacag     1140

tggttcaaag tttttttctt ccatttcagg tgtcgtga                             1178


<210>  60
<211>  402
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: SFFV promoter

<400>  60
gtaacgccat tttgcaaggc atggaaaaat accaaaccaa gaatagagaa gttcagatca       60

agggcgggta catgaaaata gctaacgttg ggccaaacag gatatctgcg gtgagcagtt      120

tcggccccgg cccggggcca agaacagatg gtcaccgcag tttcggcccc ggcccgaggc      180

caagaacaga tggtccccag atatggccca accctcagca gtttcttaag acccatcaga      240

tgtttccagg ctcccccaag gacctgaaat gaccctgcgc cttatttgaa ttaaccaatc      300

agcctgcttc tcgcttctgt tcgcgcgctt ctgcttcccg agctctataa aagagctcac      360

aacccctcac tcggcgcgcc agtcctccga cagactgagt cg                         402


<210>  61
<211>  57
<212>  DNA
<213>  Teschovirus sp.


<220>
<221>  misc_feature
<223>  2A peptide from porcine teschovirus

<400>  61
gccacgaact tctctctgtt aaagcaagca ggagacgtgg aagaaaaccc cggtcct          57


<210>  62
<211>  49
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Synthetic poly(A) signal

<400>  62
aataaaatcg ctatccatcg aagatggatg tgtgttggtt ttttgtgtg                   49


<210>  63
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: PAM, Canonical PAM


<220>
<221>  misc_feature
<222>  (1)..(21)
<223>  n is any nucleotide and repeats 19 times and up to 21 times

<220>
<221>  misc_feature
<222>  (22)..(22)
<223>  n is a, c, g, or t

<400>  63
nnnnnnnnnn nnnnnnnnnn nnrg                                              24


<210>  64
<211>  3
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: PAM, SpCas9 PAM


<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  n is a, c, g, or t

<400>  64
nrg                                                                      3


<210>  65
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: Nuclear localization signal (NLS), SV40 NLS 1

<400>  65

Pro Lys Lys Lys Arg Lys Val 
1               5           


<210>  66
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: NLS, SV40 NLS 2

<400>  66

Pro Lys Lys Lys Arg Arg Val 
1               5           


<210>  67
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: NLS, Nucleoplasmin NLS

<400>  67

Lys Arg Pro Ala Ala Thr Lys Lys Ala Gly Gln Ala Lys Lys Lys Lys 
1               5                   10                  15      


<210>  68
<211>  225
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: I53, i53 (DNA)

<400>  68
atgctgatct tcgtgaagac cctgaccggc aagaccatca ccctggaggt ggagcccagc       60

gacaccatcg agaacgtgaa ggccaagatc caggacaagg agggcatccc ccccgaccag      120

cagaggctgg ccttcgccgg caagagcctg gaggacggca ggaccctgag cgactacaac      180

atcctgaagg acagcaagct gcaccccctg ctgaggctga ggtga                      225


<210>  69
<211>  225
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: I53 mRNA, i53 (RNA)

<400>  69
augcugaucu ucgugaagac ccugaccggc aagaccauca cccuggaggu ggagcccagc       60

gacaccaucg agaacgugaa ggccaagauc caggacaagg agggcauccc ccccgaccag      120

cagaggcugg ccuucgccgg caagagccug gaggacggca ggacccugag cgacuacaac      180

auccugaagg acagcaagcu gcacccccug cugaggcuga gguga                      225


<210>  70
<211>  74
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: I53, i53 (aa)

<400>  70

Met Leu Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu 
1               5                   10                  15      


Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp 
            20                  25                  30          


Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ala Phe Ala Gly Lys 
        35                  40                  45              


Ser Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Leu Lys Asp 
    50                  55                  60                  


Ser Lys Leu His Pro Leu Leu Arg Leu Arg 
65                  70                  


<210>  71
<211>  222
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: DM mRNA, I53-DM (RNA)

<400>  71
auguugauuu ucgugaaaac ccuuaccggg aaaaccauca cccucgaggu ugaacccucg       60

gauacgauag aaaauguaaa ggccaagauc caggauaagg aaggaauucc uccugaucag      120

cagagacugg ccuuugcugg caaaucgcug gaagauggac guacuuuguc ugacuacaau      180

auucuaaagg acucuaaacu ucaucuagug uugagacuuc gu                         222


<210>  72
<211>  228
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: A10 (DNA)

<400>  72
atgcagattt acgtgaagac ctttgcccgg aagcccatca ccctcgaggt tgaaccctcg       60

gatacgatag aaaatgtaaa ggccaagatc caggataagg aaggaattcc tcctgatcag      120

cagcgactga tctttgctga aatgcggctg gaagatggac gtactttgtc tgactacaat      180

attaaaaacg actctactct ttttcttgtg ttgaaaaata gtgttact                   228


<210>  73
<211>  228
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: A10 (RNA)

<400>  73
augcagauuu acgugaagac cuuugcccgg aagcccauca cccucgaggu ugaacccucg       60

gauacgauag aaaauguaaa ggccaagauc caggauaagg aaggaauucc uccugaucag      120

cagcgacuga ucuuugcuga aaugcggcug gaagauggac guacuuuguc ugacuacaau      180

auuaaaaacg acucuacucu uuuucuugug uugaaaaaua guguuacu                   228


<210>  74
<211>  76
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: A10 (aa)

<400>  74

Met Gln Ile Tyr Val Lys Thr Phe Ala Arg Lys Pro Ile Thr Leu Glu 
1               5                   10                  15      


Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp 
            20                  25                  30          


Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Glu Met 
        35                  40                  45              


Arg Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Lys Asn Asp 
    50                  55                  60                  


Ser Thr Leu Phe Leu Val Leu Lys Asn Ser Val Thr 
65                  70                  75      


<210>  75
<211>  228
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: A11 (DNA)

<400>  75
atgctgattt tcgtgaccac cgatatgggg atgacaatct cactcgaggt tgaaccctcg       60

gatacgatag aaaatgtaaa ggccaagatc caggataagg aaggaattcc tcctgatcag      120

cagagactga tctttggtga caaggatctg gaagatggac gtactttgtc tgactacaat      180

attcaaaagg agtctagcct taatcttgtg ctgaaacttc gtggtggt                   228


<210>  76
<211>  228
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: A11 (RNA)

<400>  76
augcugauuu ucgugaccac cgauaugggg augacaaucu cacucgaggu ugaacccucg       60

gauacgauag aaaauguaaa ggccaagauc caggauaagg aaggaauucc uccugaucag      120

cagagacuga ucuuugguga caaggaucug gaagauggac guacuuuguc ugacuacaau      180

auucaaaagg agucuagccu uaaucuugug cugaaacuuc gugguggu                   228


<210>  77
<211>  76
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: A11 (aa)

<400>  77

Met Leu Ile Phe Val Thr Thr Asp Met Gly Met Thr Ile Ser Leu Glu 
1               5                   10                  15      


Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp 
            20                  25                  30          


Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Gly Asp Lys 
        35                  40                  45              


Asp Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu 
    50                  55                  60                  


Ser Ser Leu Asn Leu Val Leu Lys Leu Arg Gly Gly 
65                  70                  75      


<210>  78
<211>  228
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: C08 (DNA)

<400>  78
atgcagattt tcgtgaccac cgatatgtgg atgagaatct cactcgaggt tgaaccctcg       60

gatacgatag aaaatgtaaa ggccaagatc caggataagg aaggaattcc tcctgatcag      120

cagagactga tctttggtga caaggatctg gaagatggac gtactttgtc tgactacaat      180

attcaaaagg agtctagcct taatcttgtg ctgaaccttc gtggtggt                   228


<210>  79
<211>  228
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: C08 (RNA)

<400>  79
augcagauuu ucgugaccac cgauaugugg augagaaucu cacucgaggu ugaacccucg       60

gauacgauag aaaauguaaa ggccaagauc caggauaagg aaggaauucc uccugaucag      120

cagagacuga ucuuugguga caaggaucug gaagauggac guacuuuguc ugacuacaau      180

auucaaaagg agucuagccu uaaucuugug cugaaccuuc gugguggu                   228


<210>  80
<211>  76
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: C08 (aa)

<400>  80

Met Gln Ile Phe Val Thr Thr Asp Met Trp Met Arg Ile Ser Leu Glu 
1               5                   10                  15      


Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp 
            20                  25                  30          


Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Gly Asp Lys 
        35                  40                  45              


Asp Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu 
    50                  55                  60                  


Ser Ser Leu Asn Leu Val Leu Asn Leu Arg Gly Gly 
65                  70                  75      


<210>  81
<211>  228
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: G08 (DNA)

<400>  81
atgttgattt tcgtgaaaac ccttaccggg aaaaccatca ccctcgaggt tgaaccctcg       60

gatacgatag aaaatgtaaa ggccaagatc caggataagg aaggaattcc tcctgatcag      120

cagagactga tctttgctgg caaatcgctg gaagatggac gtactttgtc tgactacaat      180

attctaaagg actctaaact tcatcctctg ttgagacttc gtggtggt                   228


<210>  82
<211>  228
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: G08 (RNA)

<400>  82
auguugauuu ucgugaaaac ccuuaccggg aaaaccauca cccucgaggu ugaacccucg       60

gauacgauag aaaauguaaa ggccaagauc caggauaagg aaggaauucc uccugaucag      120

cagagacuga ucuuugcugg caaaucgcug gaagauggac guacuuuguc ugacuacaau      180

auucuaaagg acucuaaacu ucauccucug uugagacuuc gugguggu                   228


<210>  83
<211>  76
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: G08 (aa)

<400>  83

Met Leu Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu 
1               5                   10                  15      


Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp 
            20                  25                  30          


Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys 
        35                  40                  45              


Ser Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Leu Lys Asp 
    50                  55                  60                  


Ser Lys Leu His Pro Leu Leu Arg Leu Arg Gly Gly 
65                  70                  75      


<210>  84
<211>  228
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: H04 (DNA)

<400>  84
atgcgaatta tcgtgaaaac ctttatgcgg aagccgatca cgctcgaggt tgaaccctcg       60

gatacgatag aaaatgtaaa ggccaagatc caggataagg aaggaattcc tcctgatcag      120

cagagactgt attttgcggc cagtcagctg gaagatggac gtactttgtc tgactacaat      180

attcaaaagg agtctactct tcttcttgtg gtaaggctgc tccgcgtt                   228


<210>  85
<211>  228
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: H04 (RNA)

<400>  85
augcgaauua ucgugaaaac cuuuaugcgg aagccgauca cgcucgaggu ugaacccucg       60

gauacgauag aaaauguaaa ggccaagauc caggauaagg aaggaauucc uccugaucag      120

cagagacugu auuuugcggc cagucagcug gaagauggac guacuuuguc ugacuacaau      180

auucaaaagg agucuacucu ucuucuugug guaaggcugc uccgcguu                   228


<210>  86
<211>  76
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: H04 (aa)

<400>  86

Met Arg Ile Ile Val Lys Thr Phe Met Arg Lys Pro Ile Thr Leu Glu 
1               5                   10                  15      


Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp 
            20                  25                  30          


Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Tyr Phe Ala Ala Ser 
        35                  40                  45              


Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu 
    50                  55                  60                  


Ser Thr Leu Leu Leu Val Val Arg Leu Leu Arg Val 
65                  70                  75      


<210>  87
<211>  222
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: I53 alt (DNA)

<400>  87
atgttgattt tcgtgaaaac ccttaccggg aaaaccatca ccctcgaggt tgaaccctcg       60

gatacgatag aaaatgtaaa ggccaagatc caggataagg aaggaattcc tcctgatcag      120

cagagactgg cctttgctgg caaatcgctg gaagatggac gtactttgtc tgactacaat      180

attctaaagg actctaaact tcatcctctg ttgagacttc gt                         222


<210>  88
<211>  222
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: I53 alt (RNA)

<400>  88
auguugauuu ucgugaaaac ccuuaccggg aaaaccauca cccucgaggu ugaacccucg       60

gauacgauag aaaauguaaa ggccaagauc caggauaagg aaggaauucc uccugaucag      120

cagagacugg ccuuugcugg caaaucgcug gaagauggac guacuuuguc ugacuacaau      180

auucuaaagg acucuaaacu ucauccucug uugagacuuc gu                         222


<210>  89
<211>  291
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: FLAG-tagged i53 DNA

<400>  89
atggactaca aagacgatga cgataaagcc gccagtttaa acggcgcgcc attaattaag       60

gatccaatgt tgattttcgt gaaaaccctt accgggaaaa ccatcaccct cgaggttgaa      120

ccctcggata cgatagaaaa tgtaaaggcc aagatccagg ataaggaagg aattcctcct      180

gatcagcaga gactggcctt tgctggcaaa tcgctggaag atggacgtac tttgtctgac      240

tacaatattc taaaggactc taaacttcat cctctgttga gacttcgttg a               291


<210>  90
<211>  291
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: FLAG-tagged i53 RNA

<400>  90
auggacuaca aagacgauga cgauaaagcc gccaguuuaa acggcgcgcc auuaauuaag       60

gauccaaugu ugauuuucgu gaaaacccuu accgggaaaa ccaucacccu cgagguugaa      120

cccucggaua cgauagaaaa uguaaaggcc aagauccagg auaaggaagg aauuccuccu      180

gaucagcaga gacuggccuu ugcuggcaaa ucgcuggaag auggacguac uuugucugac      240

uacaauauuc uaaaggacuc uaaacuucau ccucuguuga gacuucguug a               291


<210>  91
<211>  39
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Linker (DNA)

<400>  91
gccgccagtt taaacggcgc gccattaatt aaggatcca                              39


<210>  92
<211>  39
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Linker (RNA)

<400>  92
gccgccaguu uaaacggcgc gccauuaauu aaggaucca                              39


<210>  93
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: Linker

<400>  93

Ala Ala Ser Leu Asn Gly Ala Pro Leu Ile Lys Asp Pro 
1               5                   10              


<210>  94
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: Protein tag, 6xHis

<400>  94

His His His His His His 
1               5       


<210>  95
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: Protein tag, Flag

<400>  95

Met Asp Tyr Lys Asp Asp Asp Asp Lys 
1               5                   


<210>  96
<211>  24
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Protein tag, FLAG (DNA)

<400>  96
gactacaaag acgatgacga taaa                                              24


<210>  97
<211>  24
<212>  RNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Protein tag, FLAG (RNA)

<400>  97
gacuacaaag acgaugacga uaaa                                              24


<210>  98
<211>  4435
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, HBB locus LHA to RHA (used for E6V to E6, 
       AAV.323)

<400>  98
cttgctttga caattttggt ctttcagaat actataaata taacctatat tataatttca       60

taaagtctgt gcattttctt tgacccagga tatttgcaaa agacatattc aaacttccgc      120

agaacacttt atttcacata tacatgcctc ttatatcagg gatgtgaaac agggtcttga      180

aaactgtcta aatctaaaac aatgctaatg caggtttaaa tttaataaaa taaaatccaa      240

aatctaacag ccaagtcaaa tctgcatgtt ttaacattta aaatatttta aagacgtctt      300

ttcccaggat tcaacatgtg aaatcttttc tcagggatac acgtgtgcct agatcctcat      360

tgctttagtt ttttacagag gaatgaatat aaaaagaaaa tacttaaatt ttatccctct      420

tacctctata atcatacata ggcataattt tttaacctag gctccagata gccatagaag      480

aaccaaacac tttctgcgtg tgtgagaata atcagagtga gattttttca caagtacctg      540

atgagggttg agacaggtag aaaaagtgag agatctctat ttatttagca ataatagaga      600

aagcatttaa gagaataaag caatggaaat aagaaatttg taaatttcct tctgataact      660

agaaatagag gatccagttt cttttggtta acctaaattt tatttcattt tattgtttta      720

ttttatttta ttttatttta ttttgtgtaa tcgtagtttc agagtgttag agctgaaagg      780

aagaagtagg agaaacatgc aaagtaaaag tataacactt tccttactaa accgacatgg      840

gtttccaggt aggggcagga ttcaggatga ctgacagggc ccttagggaa cactgagacc      900

ctacgctgac ctcataaatg cttgctacct ttgctgtttt aattacatct tttaatagca      960

ggaagcagaa ctctgcactt caaaagtttt tcctcacctg aggagttaat ttagtacaag     1020

gggaaaaagt acagggggat gggagaaagg cgatcacgtt gggaagctat agagaaagaa     1080

gagtaaattt tagtaaagga ggtttaaaca aacaaaatat aaagagaaat aggaacttga     1140

atcaaggaaa tgattttaaa acgcagtatt cttagtggac tagaggaaaa aaataatctg     1200

agccaagtag aagacctttt cccctcctac ccctactttc taagtcacag aggctttttg     1260

ttcccccaga cactcttgca gattagtcca ggcagaaaca gttagatgtc cccagttaac     1320

ctcctatttg acaccactga ttaccccatt gatagtcaca ctttgggttg taagtgactt     1380

tttatttatt tgtatttttg actgcattaa gaggtctcta gttttttatc tcttgtttcc     1440

caaaacctaa taagtaacta atgcacagag cacattgatt tgtatttatt ctatttttag     1500

acataattta ttagcatgca tgagcaaatt aagaaaaaca acaacaaatg aatgcatata     1560

tatgtatatg tatgtgtgta tatatacaca catatatata tatatttttt cttttcttac     1620

cagaaggttt taatccaaat aaggagaaga tatgcttaga accgaggtag agttttcatc     1680

cattctgtcc tgtaagtatt ttgcatattc tggagacgca ggaagagatc catctacata     1740

tcccaaagct gaattatggt agacaaaact cttccacttt tagtgcatca acttcttatt     1800

tgtgtaataa gaaaattggg aaaacgatct tcaatatgct taccaagctg tgattccaaa     1860

tattacgtaa atacacttgc aaaggaggat gtttttagta gcaatttgta ctgatggtat     1920

ggggccaaga gatatatctt agagggaggg ctgagggttt gaagtccaac tcctaagcca     1980

gtgccagaag agccaaggac aggtacggct gtcatcactt agacctcacc ctgtggagcc     2040

acaccctagg gttggccaat ctactcccag gagcagggag ggcaggagcc agggctgggc     2100

ataaaagtca gggcagagcc atctattgct tacatttgct tctgacacaa ctgtgttcac     2160

tagcaacctc aaacagacac catggtgcat ctgactcctg aagaaaaatc cgctgtcact     2220

gccctgtggg gcaaggtgaa cgtggatgaa gttggtggtg aggccctggg caggttggta     2280

tcaaggttac aagacaggtt taaggagacc aatagaaact gggcatgtgg agacagagaa     2340

gactcttggg tttctgatag gcactgactc tctctgccta ttggtctatt ttcccaccct     2400

taggctgctg gtggtctacc cttggaccca gaggttcttt gagtcctttg gggatctgtc     2460

cactcctgat gctgttatgg gcaaccctaa ggtgaaggct catggcaaga aagtgctcgg     2520

tgcctttagt gatggcctgg ctcacctgga caacctcaag ggcacctttg ccacactgag     2580

tgagctgcac tgtgacaagc tgcacgtgga tcctgagaac ttcagggtga gtctatggga     2640

cgcttgatgt tttctttccc cttcttttct atggttaagt tcatgtcata ggaaggggat     2700

aagtaacagg gtacagttta gaatgggaaa cagacgaatg attgcatcag tgtggaagtc     2760

tcaggatcgt tttagtttct tttatttgct gttcataaca attgttttct tttgtttaat     2820

tcttgctttc tttttttttc ttctccgcaa tttttactat tatacttaat gccttaacat     2880

tgtgtataac aaaaggaaat atctctgaga tacattaagt aacttaaaaa aaaactttac     2940

acagtctgcc tagtacatta ctatttggaa tatatgtgtg cttatttgca tattcataat     3000

ctccctactt tattttcttt tatttttaat tgatacataa tcattataca tatttatggg     3060

ttaaagtgta atgttttaat atgtgtacac atattgacca aatcagggta attttgcatt     3120

tgtaatttta aaaaatgctt tcttctttta atatactttt ttgtttatct tatttctaat     3180

actttcccta atctctttct ttcagggcaa taatgataca atgtatcatg cctctttgca     3240

ccattctaaa gaataacagt gataatttct gggttaaggc aatagcaata tctctgcata     3300

taaatatttc tgcatataaa ttgtaactga tgtaagaggt ttcatattgc taatagcagc     3360

tacaatccag ctaccattct gcttttattt tatggttggg ataaggctgg attattctga     3420

gtccaagcta ggcccttttg ctaatcatgt tcatacctct tatcttcctc ccacagctcc     3480

tgggcaacgt gctggtctgt gtgctggccc atcactttgg caaagaattc accccaccag     3540

tgcaggctgc ctatcagaaa gtggtggctg gtgtggctaa tgccctggcc cacaagtatc     3600

actaagctcg ctttcttgct gtccaatttc tattaaaggt tcctttgttc cctaagtcca     3660

actactaaac tgggggatat tatgaagggc cttgagcatc tggattctgc ctaataaaaa     3720

acatttattt tcattgcaat gatgtattta aattatttct gaatatttta ctaaaaaggg     3780

aatgtgggag gtcagtgcat ttaaaacata aagaaatgaa gagctagttc aaaccttggg     3840

aaaatacact atatcttaaa ctccatgaaa gaaggtgagg ctgcaaacag ctaatgcaca     3900

ttggcaacag cccctgatgc atatgcctta ttcatccctc agaaaaggat tcaagtagag     3960

gcttgatttg gaggttaaag ttttgctatg ctgtatttta cattacttat tgttttagct     4020

gtcctcatga atgtcttttc actacccatt tgcttatcct gcatctctca gccttgactc     4080

cactcagttc tcttgcttag agataccacc tttcccctga agtgttcctt ccatgtttta     4140

cggcgagatg gtttctcctc gcctggccac tcagccttag ttgtctctgt tgtcttatag     4200

aggtctactt gaagaaggaa aaacaggggt catggtttga ctgtcctgtg agcccttctt     4260

ccctgcctcc cccactcaca gtgacccgga atctgcagtg ctagtctccc ggaactatca     4320

ctctttcaca gtctgctttg gaaggactgg gcttagtatg aaaagttagg actgagaaga     4380

atttgaaagg cggctttttg tagcttgata ttcactactg tcttattacc ctgtc          4435


<210>  99
<211>  2199
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, HBB locus LHA (used for E6V to E6, AAV.323)

<400>  99
cttgctttga caattttggt ctttcagaat actataaata taacctatat tataatttca       60

taaagtctgt gcattttctt tgacccagga tatttgcaaa agacatattc aaacttccgc      120

agaacacttt atttcacata tacatgcctc ttatatcagg gatgtgaaac agggtcttga      180

aaactgtcta aatctaaaac aatgctaatg caggtttaaa tttaataaaa taaaatccaa      240

aatctaacag ccaagtcaaa tctgcatgtt ttaacattta aaatatttta aagacgtctt      300

ttcccaggat tcaacatgtg aaatcttttc tcagggatac acgtgtgcct agatcctcat      360

tgctttagtt ttttacagag gaatgaatat aaaaagaaaa tacttaaatt ttatccctct      420

tacctctata atcatacata ggcataattt tttaacctag gctccagata gccatagaag      480

aaccaaacac tttctgcgtg tgtgagaata atcagagtga gattttttca caagtacctg      540

atgagggttg agacaggtag aaaaagtgag agatctctat ttatttagca ataatagaga      600

aagcatttaa gagaataaag caatggaaat aagaaatttg taaatttcct tctgataact      660

agaaatagag gatccagttt cttttggtta acctaaattt tatttcattt tattgtttta      720

ttttatttta ttttatttta ttttgtgtaa tcgtagtttc agagtgttag agctgaaagg      780

aagaagtagg agaaacatgc aaagtaaaag tataacactt tccttactaa accgacatgg      840

gtttccaggt aggggcagga ttcaggatga ctgacagggc ccttagggaa cactgagacc      900

ctacgctgac ctcataaatg cttgctacct ttgctgtttt aattacatct tttaatagca      960

ggaagcagaa ctctgcactt caaaagtttt tcctcacctg aggagttaat ttagtacaag     1020

gggaaaaagt acagggggat gggagaaagg cgatcacgtt gggaagctat agagaaagaa     1080

gagtaaattt tagtaaagga ggtttaaaca aacaaaatat aaagagaaat aggaacttga     1140

atcaaggaaa tgattttaaa acgcagtatt cttagtggac tagaggaaaa aaataatctg     1200

agccaagtag aagacctttt cccctcctac ccctactttc taagtcacag aggctttttg     1260

ttcccccaga cactcttgca gattagtcca ggcagaaaca gttagatgtc cccagttaac     1320

ctcctatttg acaccactga ttaccccatt gatagtcaca ctttgggttg taagtgactt     1380

tttatttatt tgtatttttg actgcattaa gaggtctcta gttttttatc tcttgtttcc     1440

caaaacctaa taagtaacta atgcacagag cacattgatt tgtatttatt ctatttttag     1500

acataattta ttagcatgca tgagcaaatt aagaaaaaca acaacaaatg aatgcatata     1560

tatgtatatg tatgtgtgta tatatacaca catatatata tatatttttt cttttcttac     1620

cagaaggttt taatccaaat aaggagaaga tatgcttaga accgaggtag agttttcatc     1680

cattctgtcc tgtaagtatt ttgcatattc tggagacgca ggaagagatc catctacata     1740

tcccaaagct gaattatggt agacaaaact cttccacttt tagtgcatca acttcttatt     1800

tgtgtaataa gaaaattggg aaaacgatct tcaatatgct taccaagctg tgattccaaa     1860

tattacgtaa atacacttgc aaaggaggat gtttttagta gcaatttgta ctgatggtat     1920

ggggccaaga gatatatctt agagggaggg ctgagggttt gaagtccaac tcctaagcca     1980

gtgccagaag agccaaggac aggtacggct gtcatcactt agacctcacc ctgtggagcc     2040

acaccctagg gttggccaat ctactcccag gagcagggag ggcaggagcc agggctgggc     2100

ataaaagtca gggcagagcc atctattgct tacatttgct tctgacacaa ctgtgttcac     2160

tagcaacctc aaacagacac catggtgcat ctgactcct                            2199


<210>  100
<211>  2218
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA , HBB locus RHA (used for E6V to E6, 
       AAV.323)

<400>  100
actgccctgt ggggcaaggt gaacgtggat gaagttggtg gtgaggccct gggcaggttg       60

gtatcaaggt tacaagacag gtttaaggag accaatagaa actgggcatg tggagacaga      120

gaagactctt gggtttctga taggcactga ctctctctgc ctattggtct attttcccac      180

ccttaggctg ctggtggtct acccttggac ccagaggttc tttgagtcct ttggggatct      240

gtccactcct gatgctgtta tgggcaaccc taaggtgaag gctcatggca agaaagtgct      300

cggtgccttt agtgatggcc tggctcacct ggacaacctc aagggcacct ttgccacact      360

gagtgagctg cactgtgaca agctgcacgt ggatcctgag aacttcaggg tgagtctatg      420

ggacgcttga tgttttcttt ccccttcttt tctatggtta agttcatgtc ataggaaggg      480

gataagtaac agggtacagt ttagaatggg aaacagacga atgattgcat cagtgtggaa      540

gtctcaggat cgttttagtt tcttttattt gctgttcata acaattgttt tcttttgttt      600

aattcttgct ttcttttttt ttcttctccg caatttttac tattatactt aatgccttaa      660

cattgtgtat aacaaaagga aatatctctg agatacatta agtaacttaa aaaaaaactt      720

tacacagtct gcctagtaca ttactatttg gaatatatgt gtgcttattt gcatattcat      780

aatctcccta ctttattttc ttttattttt aattgataca taatcattat acatatttat      840

gggttaaagt gtaatgtttt aatatgtgta cacatattga ccaaatcagg gtaattttgc      900

atttgtaatt ttaaaaaatg ctttcttctt ttaatatact tttttgttta tcttatttct      960

aatactttcc ctaatctctt tctttcaggg caataatgat acaatgtatc atgcctcttt     1020

gcaccattct aaagaataac agtgataatt tctgggttaa ggcaatagca atatctctgc     1080

atataaatat ttctgcatat aaattgtaac tgatgtaaga ggtttcatat tgctaatagc     1140

agctacaatc cagctaccat tctgctttta ttttatggtt gggataaggc tggattattc     1200

tgagtccaag ctaggccctt ttgctaatca tgttcatacc tcttatcttc ctcccacagc     1260

tcctgggcaa cgtgctggtc tgtgtgctgg cccatcactt tggcaaagaa ttcaccccac     1320

cagtgcaggc tgcctatcag aaagtggtgg ctggtgtggc taatgccctg gcccacaagt     1380

atcactaagc tcgctttctt gctgtccaat ttctattaaa ggttcctttg ttccctaagt     1440

ccaactacta aactggggga tattatgaag ggccttgagc atctggattc tgcctaataa     1500

aaaacattta ttttcattgc aatgatgtat ttaaattatt tctgaatatt ttactaaaaa     1560

gggaatgtgg gaggtcagtg catttaaaac ataaagaaat gaagagctag ttcaaacctt     1620

gggaaaatac actatatctt aaactccatg aaagaaggtg aggctgcaaa cagctaatgc     1680

acattggcaa cagcccctga tgcatatgcc ttattcatcc ctcagaaaag gattcaagta     1740

gaggcttgat ttggaggtta aagttttgct atgctgtatt ttacattact tattgtttta     1800

gctgtcctca tgaatgtctt ttcactaccc atttgcttat cctgcatctc tcagccttga     1860

ctccactcag ttctcttgct tagagatacc acctttcccc tgaagtgttc cttccatgtt     1920

ttacggcgag atggtttctc ctcgcctggc cactcagcct tagttgtctc tgttgtctta     1980

tagaggtcta cttgaagaag gaaaaacagg ggtcatggtt tgactgtcct gtgagccctt     2040

cttccctgcc tcccccactc acagtgaccc ggaatctgca gtgctagtct cccggaacta     2100

tcactctttc acagtctgct ttggaaggac tgggcttagt atgaaaagtt aggactgaga     2160

agaatttgaa aggcggcttt ttgtagcttg atattcacta ctgtcttatt accctgtc       2218


<210>  101
<211>  1421
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, HBB exons 1-3

<400>  101
atggtgcatc tgactcctga agaaaaatcc gctgtcactg ccctgtgggg caaggtgaac       60

gtggatgaag ttggtggtga ggccctgggc aggttggtat caaggttaca agacaggttt      120

aaggagacca atagaaactg ggcatgtgga gacagagaag actcttgggt ttctgatagg      180

cactgactct ctctgcctat tggtctattt tcccaccctt aggctgctgg tggtctaccc      240

ttggacccag aggttctttg agtcctttgg ggatctgtcc actcctgatg ctgttatggg      300

caaccctaag gtgaaggctc atggcaagaa agtgctcggt gcctttagtg atggcctggc      360

tcacctggac aacctcaagg gcacctttgc cacactgagt gagctgcact gtgacaagct      420

gcacgtggat cctgagaact tcagggtgag tctatgggac gcttgatgtt ttctttcccc      480

ttcttttcta tggttaagtt catgtcatag gaaggggata agtaacaggg tacagtttag      540

aatgggaaac agacgaatga ttgcatcagt gtggaagtct caggatcgtt ttagtttctt      600

ttatttgctg ttcataacaa ttgttttctt ttgtttaatt cttgctttct ttttttttct      660

tctccgcaat ttttactatt atacttaatg ccttaacatt gtgtataaca aaaggaaata      720

tctctgagat acattaagta acttaaaaaa aaactttaca cagtctgcct agtacattac      780

tatttggaat atatgtgtgc ttatttgcat attcataatc tccctacttt attttctttt      840

atttttaatt gatacataat cattatacat atttatgggt taaagtgtaa tgttttaata      900

tgtgtacaca tattgaccaa atcagggtaa ttttgcattt gtaattttaa aaaatgcttt      960

cttcttttaa tatacttttt tgtttatctt atttctaata ctttccctaa tctctttctt     1020

tcagggcaat aatgatacaa tgtatcatgc ctctttgcac cattctaaag aataacagtg     1080

ataatttctg ggttaaggca atagcaatat ctctgcatat aaatatttct gcatataaat     1140

tgtaactgat gtaagaggtt tcatattgct aatagcagct acaatccagc taccattctg     1200

cttttatttt atggttggga taaggctgga ttattctgag tccaagctag gcccttttgc     1260

taatcatgtt catacctctt atcttcctcc cacagctcct gggcaacgtg ctggtctgtg     1320

tgctggccca tcactttggc aaagaattca ccccaccagt gcaggctgcc tatcagaaag     1380

tggtggctgg tgtggctaat gccctggccc acaagtatca c                         1421


<210>  102
<211>  18
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor DNA, E6V to E6 Insert

<400>  102
gaagaaaaat ccgctgtc                                                     18


<210>  103
<211>  1404
<212>  PRT
<213>  S. pyogenes


<220>
<221>  misc_feature
<223>  Wild-type S. pyogenes Cas9

<400>  103

Met Ala Pro Lys Lys Lys Arg Lys Val Gly Ser Gly Gly Ser Gly Gly 
1               5                   10                  15      


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Phe Lys Glu Asp Ile Gln Lys Ala Gln Val Ser Gly Gln Gly Asp Ser 
                725                 730                 735     


Leu His Glu His Ile Ala Asn Leu Ala Gly Ser Pro Ala Ile Lys Lys 
            740                 745                 750         


Gly Ile Leu Gln Thr Val Lys Val Val Asp Glu Leu Val Lys Val Met 
        755                 760                 765             


Gly Arg His Lys Pro Glu Asn Ile Val Ile Glu Met Ala Arg Glu Asn 
    770                 775                 780                 


Gln Thr Thr Gln Lys Gly Gln Lys Asn Ser Arg Glu Arg Met Lys Arg 
785                 790                 795                 800 


Ile Glu Glu Gly Ile Lys Glu Leu Gly Ser Gln Ile Leu Lys Glu His 
                805                 810                 815     


Pro Val Glu Asn Thr Gln Leu Gln Asn Glu Lys Leu Tyr Leu Tyr Tyr 
            820                 825                 830         


Leu Gln Asn Gly Arg Asp Met Tyr Val Asp Gln Glu Leu Asp Ile Asn 
        835                 840                 845             


Arg Leu Ser Asp Tyr Asp Val Asp His Ile Val Pro Gln Ser Phe Leu 
    850                 855                 860                 


Lys Asp Asp Ser Ile Asp Asn Lys Val Leu Thr Arg Ser Asp Lys Asn 
865                 870                 875                 880 


Arg Gly Lys Ser Asp Asn Val Pro Ser Glu Glu Val Val Lys Lys Met 
                885                 890                 895     


Lys Asn Tyr Trp Arg Gln Leu Leu Asn Ala Lys Leu Ile Thr Gln Arg 
            900                 905                 910         


Lys Phe Asp Asn Leu Thr Lys Ala Glu Arg Gly Gly Leu Ser Glu Leu 
        915                 920                 925             


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


Thr Lys His Val Ala Gln Ile Leu Asp Ser Arg Met Asn Thr Lys Tyr 
945                 950                 955                 960 


Asp Glu Asn Asp Lys Leu Ile Arg Glu Val Lys Val Ile Thr Leu Lys 
                965                 970                 975     


Ser Lys Leu Val Ser Asp Phe Arg Lys Asp Phe Gln Phe Tyr Lys Val 
            980                 985                 990         


Arg Glu Ile Asn Asn Tyr His His  Ala His Asp Ala Tyr  Leu Asn Ala 
        995                 1000                 1005             


Val Val  Gly Thr Ala Leu Ile  Lys Lys Tyr Pro Lys  Leu Glu Ser 
    1010                 1015                 1020             


Glu Phe  Val Tyr Gly Asp Tyr  Lys Val Tyr Asp Val  Arg Lys Met 
    1025                 1030                 1035             


Ile Ala  Lys Ser Glu Gln Glu  Ile Gly Lys Ala Thr  Ala Lys Tyr 
    1040                 1045                 1050             


Phe Phe  Tyr Ser Asn Ile Met  Asn Phe Phe Lys Thr  Glu Ile Thr 
    1055                 1060                 1065             


Leu Ala  Asn Gly Glu Ile Arg  Lys Arg Pro Leu Ile  Glu Thr Asn 
    1070                 1075                 1080             


Gly Glu  Thr Gly Glu Ile Val  Trp Asp Lys Gly Arg  Asp Phe Ala 
    1085                 1090                 1095             


Thr Val  Arg Lys Val Leu Ser  Met Pro Gln Val Asn  Ile Val Lys 
    1100                 1105                 1110             


Lys Thr  Glu Val Gln Thr Gly  Gly Phe Ser Lys Glu  Ser Ile Leu 
    1115                 1120                 1125             


Pro Lys  Arg Asn Ser Asp Lys  Leu Ile Ala Arg Lys  Lys Asp Trp 
    1130                 1135                 1140             


Asp Pro  Lys Lys Tyr Gly Gly  Phe Asp Ser Pro Thr  Val Ala Tyr 
    1145                 1150                 1155             


Ser Val  Leu Val Val Ala Lys  Val Glu Lys Gly Lys  Ser Lys Lys 
    1160                 1165                 1170             


Leu Lys  Ser Val Lys Glu Leu  Leu Gly Ile Thr Ile  Met Glu Arg 
    1175                 1180                 1185             


Ser Ser  Phe Glu Lys Asn Pro  Ile Asp Phe Leu Glu  Ala Lys Gly 
    1190                 1195                 1200             


Tyr Lys  Glu Val Lys Lys Asp  Leu Ile Ile Lys Leu  Pro Lys Tyr 
    1205                 1210                 1215             


Ser Leu  Phe Glu Leu Glu Asn  Gly Arg Lys Arg Met  Leu Ala Ser 
    1220                 1225                 1230             


Ala Gly  Glu Leu Gln Lys Gly  Asn Glu Leu Ala Leu  Pro Ser Lys 
    1235                 1240                 1245             


Tyr Val  Asn Phe Leu Tyr Leu  Ala Ser His Tyr Glu  Lys Leu Lys 
    1250                 1255                 1260             


Gly Ser  Pro Glu Asp Asn Glu  Gln Lys Gln Leu Phe  Val Glu Gln 
    1265                 1270                 1275             


His Lys  His Tyr Leu Asp Glu  Ile Ile Glu Gln Ile  Ser Glu Phe 
    1280                 1285                 1290             


Ser Lys  Arg Val Ile Leu Ala  Asp Ala Asn Leu Asp  Lys Val Leu 
    1295                 1300                 1305             


Ser Ala  Tyr Asn Lys His Arg  Asp Lys Pro Ile Arg  Glu Gln Ala 
    1310                 1315                 1320             


Glu Asn  Ile Ile His Leu Phe  Thr Leu Thr Asn Leu  Gly Ala Pro 
    1325                 1330                 1335             


Ala Ala  Phe Lys Tyr Phe Asp  Thr Thr Ile Asp Arg  Lys Arg Tyr 
    1340                 1345                 1350             


Thr Ser  Thr Lys Glu Val Leu  Asp Ala Thr Leu Ile  His Gln Ser 
    1355                 1360                 1365             


Ile Thr  Gly Leu Tyr Glu Thr  Arg Ile Asp Leu Ser  Gln Leu Gly 
    1370                 1375                 1380             


Gly Asp  Gly Ser Ala Gly Ser  Gly Gly Ser Gly Gly  Ser Gly Pro 
    1385                 1390                 1395             


Lys Lys  Lys Arg Lys Val 
    1400                 


<210>  104
<211>  1105
<212>  PRT
<213>  S. aureus


<220>
<221>  misc_feature
<223>  Wild-type S. aureus Cas9

<400>  104

Met His His His His His His His His Gly Ser Gly Gly Ser Gly Gly 
1               5                   10                  15      


Ser Gly Pro Lys Lys Lys Arg Lys Val Gly Ser Gly Gly Ser Gly Gly 
            20                  25                  30          


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


Val Gly Tyr Gly Ile Ile Asp Tyr Glu Thr Arg Asp Val Ile Asp Ala 
    50                  55                  60                  


Gly Val Arg Leu Phe Lys Glu Ala Asn Val Glu Asn Asn Glu Gly Arg 
65                  70                  75                  80  


Arg Ser Lys Arg Gly Ala Arg Arg Leu Lys Arg Arg Arg Arg His Arg 
                85                  90                  95      


Ile Gln Arg Val Lys Lys Leu Leu Phe Asp Tyr Asn Leu Leu Thr Asp 
            100                 105                 110         


His Ser Glu Leu Ser Gly Ile Asn Pro Tyr Glu Ala Arg Val Lys Gly 
        115                 120                 125             


Leu Ser Gln Lys Leu Ser Glu Glu Glu Phe Ser Ala Ala Leu Leu His 
    130                 135                 140                 


Leu Ala Lys Arg Arg Gly Val His Asn Val Asn Glu Val Glu Glu Asp 
145                 150                 155                 160 


Thr Gly Asn Glu Leu Ser Thr Lys Glu Gln Ile Ser Arg Asn Ser Lys 
                165                 170                 175     


Ala Leu Glu Glu Lys Tyr Val Ala Glu Leu Gln Leu Glu Arg Leu Lys 
            180                 185                 190         


Lys Asp Gly Glu Val Arg Gly Ser Ile Asn Arg Phe Lys Thr Ser Asp 
        195                 200                 205             


Tyr Val Lys Glu Ala Lys Gln Leu Leu Lys Val Gln Lys Ala Tyr His 
    210                 215                 220                 


Gln Leu Asp Gln Ser Phe Ile Asp Thr Tyr Ile Asp Leu Leu Glu Thr 
225                 230                 235                 240 


Arg Arg Thr Tyr Tyr Glu Gly Pro Gly Glu Gly Ser Pro Phe Gly Trp 
                245                 250                 255     


Lys Asp Ile Lys Glu Trp Tyr Glu Met Leu Met Gly His Cys Thr Tyr 
            260                 265                 270         


Phe Pro Glu Glu Leu Arg Ser Val Lys Tyr Ala Tyr Asn Ala Asp Leu 
        275                 280                 285             


Tyr Asn Ala Leu Asn Asp Leu Asn Asn Leu Val Ile Thr Arg Asp Glu 
    290                 295                 300                 


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


Phe Lys Gln Lys Lys Lys Pro Thr Leu Lys Gln Ile Ala Lys Glu Ile 
                325                 330                 335     


Leu Val Asn Glu Glu Asp Ile Lys Gly Tyr Arg Val Thr Ser Thr Gly 
            340                 345                 350         


Lys Pro Glu Phe Thr Asn Leu Lys Val Tyr His Asp Ile Lys Asp Ile 
        355                 360                 365             


Thr Ala Arg Lys Glu Ile Ile Glu Asn Ala Glu Leu Leu Asp Gln Ile 
    370                 375                 380                 


Ala Lys Ile Leu Thr Ile Tyr Gln Ser Ser Glu Asp Ile Gln Glu Glu 
385                 390                 395                 400 


Leu Thr Asn Leu Asn Ser Glu Leu Thr Gln Glu Glu Ile Glu Gln Ile 
                405                 410                 415     


Ser Asn Leu Lys Gly Tyr Thr Gly Thr His Asn Leu Ser Leu Lys Ala 
            420                 425                 430         


Ile Asn Leu Ile Leu Asp Glu Leu Trp His Thr Asn Asp Asn Gln Ile 
        435                 440                 445             


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


Gln Gln Lys Glu Ile Pro Thr Thr Leu Val Asp Asp Phe Ile Leu Ser 
465                 470                 475                 480 


Pro Val Val Lys Arg Ser Phe Ile Gln Ser Ile Lys Val Ile Asn Ala 
                485                 490                 495     


Ile Ile Lys Lys Tyr Gly Leu Pro Asn Asp Ile Ile Ile Glu Leu Ala 
            500                 505                 510         


Arg Glu Lys Asn Ser Lys Asp Ala Gln Lys Met Ile Asn Glu Met Gln 
        515                 520                 525             


Lys Arg Asn Arg Gln Thr Asn Glu Arg Ile Glu Glu Ile Ile Arg Thr 
    530                 535                 540                 


Thr Gly Lys Glu Asn Ala Lys Tyr Leu Ile Glu Lys Ile Lys Leu His 
545                 550                 555                 560 


Asp Met Gln Glu Gly Lys Cys Leu Tyr Ser Leu Glu Ala Ile Pro Leu 
                565                 570                 575     


Glu Asp Leu Leu Asn Asn Pro Phe Asn Tyr Glu Val Asp His Ile Ile 
            580                 585                 590         


Pro Arg Ser Val Ser Phe Asp Asn Ser Phe Asn Asn Lys Val Leu Val 
        595                 600                 605             


Lys Gln Glu Glu Asn Ser Lys Lys Gly Asn Arg Thr Pro Phe Gln Tyr 
    610                 615                 620                 


Leu Ser Ser Ser Asp Ser Lys Ile Ser Tyr Glu Thr Phe Lys Lys His 
625                 630                 635                 640 


Ile Leu Asn Leu Ala Lys Gly Lys Gly Arg Ile Ser Lys Thr Lys Lys 
                645                 650                 655     


Glu Tyr Leu Leu Glu Glu Arg Asp Ile Asn Arg Phe Ser Val Gln Lys 
            660                 665                 670         


Asp Phe Ile Asn Arg Asn Leu Val Asp Thr Arg Tyr Ala Thr Arg Gly 
        675                 680                 685             


Leu Met Asn Leu Leu Arg Ser Tyr Phe Arg Val Asn Asn Leu Asp Val 
    690                 695                 700                 


Lys Val Lys Ser Ile Asn Gly Gly Phe Thr Ser Phe Leu Arg Arg Lys 
705                 710                 715                 720 


Trp Lys Phe Lys Lys Glu Arg Asn Lys Gly Tyr Lys His His Ala Glu 
                725                 730                 735     


Asp Ala Leu Ile Ile Ala Asn Ala Asp Phe Ile Phe Lys Glu Trp Lys 
            740                 745                 750         


Lys Leu Asp Lys Ala Lys Lys Val Met Glu Asn Gln Met Phe Glu Glu 
        755                 760                 765             


Lys Gln Ala Glu Ser Met Pro Glu Ile Glu Thr Glu Gln Glu Tyr Lys 
    770                 775                 780                 


Glu Ile Phe Ile Thr Pro His Gln Ile Lys His Ile Lys Asp Phe Lys 
785                 790                 795                 800 


Asp Tyr Lys Tyr Ser His Arg Val Asp Lys Lys Pro Asn Arg Glu Leu 
                805                 810                 815     


Ile Asn Asp Thr Leu Tyr Ser Thr Arg Lys Asp Asp Lys Gly Asn Thr 
            820                 825                 830         


Leu Ile Val Asn Asn Leu Asn Gly Leu Tyr Asp Lys Asp Asn Asp Lys 
        835                 840                 845             


Leu Lys Lys Leu Ile Asn Lys Ser Pro Glu Lys Leu Leu Met Tyr His 
    850                 855                 860                 


His Asp Pro Gln Thr Tyr Gln Lys Leu Lys Leu Ile Met Glu Gln Tyr 
865                 870                 875                 880 


Gly Asp Glu Lys Asn Pro Leu Tyr Lys Tyr Tyr Glu Glu Thr Gly Asn 
                885                 890                 895     


Tyr Leu Thr Lys Tyr Ser Lys Lys Asp Asn Gly Pro Val Ile Lys Lys 
            900                 905                 910         


Ile Lys Tyr Tyr Gly Asn Lys Leu Asn Ala His Leu Asp Ile Thr Asp 
        915                 920                 925             


Asp Tyr Pro Asn Ser Arg Asn Lys Val Val Lys Leu Ser Leu Lys Pro 
    930                 935                 940                 


Tyr Arg Phe Asp Val Tyr Leu Asp Asn Gly Val Tyr Lys Phe Val Thr 
945                 950                 955                 960 


Val Lys Asn Leu Asp Val Ile Lys Lys Glu Asn Tyr Tyr Glu Val Asn 
                965                 970                 975     


Ser Lys Cys Tyr Glu Glu Ala Lys Lys Leu Lys Lys Ile Ser Asn Gln 
            980                 985                 990         


Ala Glu Phe Ile Ala Ser Phe Tyr  Asn Asn Asp Leu Ile  Lys Ile Asn 
        995                 1000                 1005             


Gly Glu  Leu Tyr Arg Val Ile  Gly Val Asn Asn Asp  Leu Leu Asn 
    1010                 1015                 1020             


Arg Ile  Glu Val Asn Met Ile  Asp Ile Thr Tyr Arg  Glu Tyr Leu 
    1025                 1030                 1035             


Glu Asn  Met Asn Asp Lys Arg  Pro Pro Arg Ile Ile  Lys Thr Ile 
    1040                 1045                 1050             


Ala Ser  Lys Thr Gln Ser Ile  Lys Lys Tyr Ser Thr  Asp Ile Leu 
    1055                 1060                 1065             


Gly Asn  Leu Tyr Glu Val Lys  Ser Lys Lys His Pro  Gln Ile Ile 
    1070                 1075                 1080             


Lys Lys  Gly Gly Ser Ala Gly  Ser Gly Gly Ser Gly  Gly Ser Gly 
    1085                 1090                 1095             


Pro Lys  Lys Lys Arg Lys Val  
    1100                 1105 


<210>  105
<211>  7107
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor template, Full AAV-323

<400>  105
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact      120

aggggttcct gcggccgcac gcgtcttgct ttgacaattt tggtctttca gaatactata      180

aatataacct atattataat ttcataaagt ctgtgcattt tctttgaccc aggatatttg      240

caaaagacat attcaaactt ccgcagaaca ctttatttca catatacatg cctcttatat      300

cagggatgtg aaacagggtc ttgaaaactg tctaaatcta aaacaatgct aatgcaggtt      360

taaatttaat aaaataaaat ccaaaatcta acagccaagt caaatctgca tgttttaaca      420

tttaaaatat tttaaagacg tcttttccca ggattcaaca tgtgaaatct tttctcaggg      480

atacacgtgt gcctagatcc tcattgcttt agttttttac agaggaatga atataaaaag      540

aaaatactta aattttatcc ctcttacctc tataatcata cataggcata attttttaac      600

ctaggctcca gatagccata gaagaaccaa acactttctg cgtgtgtgag aataatcaga      660

gtgagatttt ttcacaagta cctgatgagg gttgagacag gtagaaaaag tgagagatct      720

ctatttattt agcaataata gagaaagcat ttaagagaat aaagcaatgg aaataagaaa      780

tttgtaaatt tccttctgat aactagaaat agaggatcca gtttcttttg gttaacctaa      840

attttatttc attttattgt tttattttat tttattttat tttattttgt gtaatcgtag      900

tttcagagtg ttagagctga aaggaagaag taggagaaac atgcaaagta aaagtataac      960

actttcctta ctaaaccgac atgggtttcc aggtaggggc aggattcagg atgactgaca     1020

gggcccttag ggaacactga gaccctacgc tgacctcata aatgcttgct acctttgctg     1080

ttttaattac atcttttaat agcaggaagc agaactctgc acttcaaaag tttttcctca     1140

cctgaggagt taatttagta caaggggaaa aagtacaggg ggatgggaga aaggcgatca     1200

cgttgggaag ctatagagaa agaagagtaa attttagtaa aggaggttta aacaaacaaa     1260

atataaagag aaataggaac ttgaatcaag gaaatgattt taaaacgcag tattcttagt     1320

ggactagagg aaaaaaataa tctgagccaa gtagaagacc ttttcccctc ctacccctac     1380

tttctaagtc acagaggctt tttgttcccc cagacactct tgcagattag tccaggcaga     1440

aacagttaga tgtccccagt taacctccta tttgacacca ctgattaccc cattgatagt     1500

cacactttgg gttgtaagtg actttttatt tatttgtatt tttgactgca ttaagaggtc     1560

tctagttttt tatctcttgt ttcccaaaac ctaataagta actaatgcac agagcacatt     1620

gatttgtatt tattctattt ttagacataa tttattagca tgcatgagca aattaagaaa     1680

aacaacaaca aatgaatgca tatatatgta tatgtatgtg tgtatatata cacacatata     1740

tatatatatt ttttcttttc ttaccagaag gttttaatcc aaataaggag aagatatgct     1800

tagaaccgag gtagagtttt catccattct gtcctgtaag tattttgcat attctggaga     1860

cgcaggaaga gatccatcta catatcccaa agctgaatta tggtagacaa aactcttcca     1920

cttttagtgc atcaacttct tatttgtgta ataagaaaat tgggaaaacg atcttcaata     1980

tgcttaccaa gctgtgattc caaatattac gtaaatacac ttgcaaagga ggatgttttt     2040

agtagcaatt tgtactgatg gtatggggcc aagagatata tcttagaggg agggctgagg     2100

gtttgaagtc caactcctaa gccagtgcca gaagagccaa ggacaggtac ggctgtcatc     2160

acttagacct caccctgtgg agccacaccc tagggttggc caatctactc ccaggagcag     2220

ggagggcagg agccagggct gggcataaaa gtcagggcag agccatctat tgcttacatt     2280

tgcttctgac acaactgtgt tcactagcaa cctcaaacag acaccatggt gcatctgact     2340

cctgaagaaa aatccgctgt cactgccctg tggggcaagg tgaacgtgga tgaagttggt     2400

ggtgaggccc tgggcaggtt ggtatcaagg ttacaagaca ggtttaagga gaccaataga     2460

aactgggcat gtggagacag agaagactct tgggtttctg ataggcactg actctctctg     2520

cctattggtc tattttccca cccttaggct gctggtggtc tacccttgga cccagaggtt     2580

ctttgagtcc tttggggatc tgtccactcc tgatgctgtt atgggcaacc ctaaggtgaa     2640

ggctcatggc aagaaagtgc tcggtgcctt tagtgatggc ctggctcacc tggacaacct     2700

caagggcacc tttgccacac tgagtgagct gcactgtgac aagctgcacg tggatcctga     2760

gaacttcagg gtgagtctat gggacgcttg atgttttctt tccccttctt ttctatggtt     2820

aagttcatgt cataggaagg ggataagtaa cagggtacag tttagaatgg gaaacagacg     2880

aatgattgca tcagtgtgga agtctcagga tcgttttagt ttcttttatt tgctgttcat     2940

aacaattgtt ttcttttgtt taattcttgc tttctttttt tttcttctcc gcaattttta     3000

ctattatact taatgcctta acattgtgta taacaaaagg aaatatctct gagatacatt     3060

aagtaactta aaaaaaaact ttacacagtc tgcctagtac attactattt ggaatatatg     3120

tgtgcttatt tgcatattca taatctccct actttatttt cttttatttt taattgatac     3180

ataatcatta tacatattta tgggttaaag tgtaatgttt taatatgtgt acacatattg     3240

accaaatcag ggtaattttg catttgtaat tttaaaaaat gctttcttct tttaatatac     3300

ttttttgttt atcttatttc taatactttc cctaatctct ttctttcagg gcaataatga     3360

tacaatgtat catgcctctt tgcaccattc taaagaataa cagtgataat ttctgggtta     3420

aggcaatagc aatatctctg catataaata tttctgcata taaattgtaa ctgatgtaag     3480

aggtttcata ttgctaatag cagctacaat ccagctacca ttctgctttt attttatggt     3540

tgggataagg ctggattatt ctgagtccaa gctaggccct tttgctaatc atgttcatac     3600

ctcttatctt cctcccacag ctcctgggca acgtgctggt ctgtgtgctg gcccatcact     3660

ttggcaaaga attcacccca ccagtgcagg ctgcctatca gaaagtggtg gctggtgtgg     3720

ctaatgccct ggcccacaag tatcactaag ctcgctttct tgctgtccaa tttctattaa     3780

aggttccttt gttccctaag tccaactact aaactggggg atattatgaa gggccttgag     3840

catctggatt ctgcctaata aaaaacattt attttcattg caatgatgta tttaaattat     3900

ttctgaatat tttactaaaa agggaatgtg ggaggtcagt gcatttaaaa cataaagaaa     3960

tgaagagcta gttcaaacct tgggaaaata cactatatct taaactccat gaaagaaggt     4020

gaggctgcaa acagctaatg cacattggca acagcccctg atgcatatgc cttattcatc     4080

cctcagaaaa ggattcaagt agaggcttga tttggaggtt aaagttttgc tatgctgtat     4140

tttacattac ttattgtttt agctgtcctc atgaatgtct tttcactacc catttgctta     4200

tcctgcatct ctcagccttg actccactca gttctcttgc ttagagatac cacctttccc     4260

ctgaagtgtt ccttccatgt tttacggcga gatggtttct cctcgcctgg ccactcagcc     4320

ttagttgtct ctgttgtctt atagaggtct acttgaagaa ggaaaaacag gggtcatggt     4380

ttgactgtcc tgtgagccct tcttccctgc ctcccccact cacagtgacc cggaatctgc     4440

agtgctagtc tcccggaact atcactcttt cacagtctgc tttggaagga ctgggcttag     4500

tatgaaaagt taggactgag aagaatttga aaggcggctt tttgtagctt gatattcact     4560

actgtcttat taccctgtcg gtaaccacgt gcggccgagg ctgcagcgtc gtcctcccta     4620

ggaaccccta gtgatggagt tggccactcc ctctctgcgc gctcgctcgc tcactgaggc     4680

cgggcgacca aaggtcgccc gacgcccggg ctttgcccgg gcggcctcag tgagcgagcg     4740

agcgcgcagc tgcctgcagg ggcgcctgat gcggtatttt ctccttacgc atctgtgcgg     4800

tatttcacac cgcatacgtc aaagcaacca tagtacgcgc cctgtagcgg cgcattaagc     4860

gcggcgggtg tggtggttac gcgcagcgtg accgctacac ttgccagcgc cctagcgccc     4920

gctcctttcg ctttcttccc ttcctttctc gccacgttcg ccggctttcc ccgtcaagct     4980

ctaaatcggg ggctcccttt agggttccga tttagtgctt tacggcacct cgaccccaaa     5040

aaacttgatt tgggtgatgg ttcacgtagt gggccatcgc cctgatagac ggtttttcgc     5100

cctttgacgt tggagtccac gttctttaat agtggactct tgttccaaac tggaacaaca     5160

ctcaacccta tctcgggcta ttcttttgat ttataaggga ttttgccgat ttcggcctat     5220

tggttaaaaa atgagctgat ttaacaaaaa tttaacgcga attttaacaa aatattaacg     5280

tttacaattt tatggtgcac tctcagtaca atctgctctg atgccgcata gttaagccag     5340

ccccgacacc cgccaacacc cgctgacgcg ccctgacggg cttgtctgct cccggcatcc     5400

gcttacagac aagctgtgac cgtctccggg agctgcatgt gtcagaggtt ttcaccgtca     5460

tcaccgaaac gcgcgagacg aaagggcctc gtgatacgcc tatttttata ggttaatgtc     5520

atgaacaata aaactgtctg cttacataaa cagtaataca aggggtgtta tgagccatat     5580

tcaacgggaa acgtcgaggc cgcgattaaa ttccaacatg gatgctgatt tatatgggta     5640

taaatgggct cgcgataatg tcgggcaatc aggtgcgaca atctatcgct tgtatgggaa     5700

gcccgatgcg ccagagttgt ttctgaaaca tggcaaaggt agcgttgcca atgatgttac     5760

agatgagatg gtcagactaa actggctgac ggaatttatg cctcttccga ccatcaagca     5820

ttttatccgt actcctgatg atgcatggtt actcaccact gcgatccccg gaaaaacagc     5880

attccaggta ttagaagaat atcctgattc aggtgaaaat attgttgatg cgctggcagt     5940

gttcctgcgc cggttgcatt cgattcctgt ttgtaattgt ccttttaaca gcgatcgcgt     6000

atttcgtctc gctcaggcgc aatcacgaat gaataacggt ttggttgatg cgagtgattt     6060

tgatgacgag cgtaatggct ggcctgttga acaagtctgg aaagaaatgc ataaactttt     6120

gccattctca ccggattcag tcgtcactca tggtgatttc tcacttgata accttatttt     6180

tgacgagggg aaattaatag gttgtattga tgttggacga gtcggaatcg cagaccgata     6240

ccaggatctt gccatcctat ggaactgcct cggtgagttt tctccttcat tacagaaacg     6300

gctttttcaa aaatatggta ttgataatcc tgatatgaat aaattgcagt ttcatttgat     6360

gctcgatgag tttttctaat ctcatgacca aaatccctta acgtgagttt tcgttccact     6420

gagcgtcaga ccccgtagaa aagatcaaag gatcttcttg agatcctttt tttctgcgcg     6480

taatctgctg cttgcaaaca aaaaaaccac cgctaccagc ggtggtttgt ttgccggatc     6540

aagagctacc aactcttttt ccgaaggtaa ctggcttcag cagagcgcag ataccaaata     6600

ctgtccttct agtgtagccg tagttaggcc accacttcaa gaactctgta gcaccgccta     6660

catacctcgc tctgctaatc ctgttaccag tggctgctgc cagtggcgat aagtcgtgtc     6720

ttaccgggtt ggactcaaga cgatagttac cggataaggc gcagcggtcg ggctgaacgg     6780

ggggttcgtg cacacagccc agcttggagc gaacgaccta caccgaactg agatacctac     6840

agcgtgagct atgagaaagc gccacgcttc ccgaagggag aaaggcggac aggtatccgg     6900

taagcggcag ggtcggaaca ggagagcgca cgagggagct tccaggggga aacgcctggt     6960

atctttatag tcctgtcggg tttcgccacc tctgacttga gcgtcgattt ttgtgatgct     7020

cgtcaggggg gcggagccta tggaaaaacg ccagcaacgc ggccttttta cggttcctgg     7080

ccttttgctg gccttttgct cacatgt                                         7107


<210>  106
<211>  130
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: AAV2 ITR for LHA (AAV.323)

<400>  106
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact      120

aggggttcct                                                             130


<210>  107
<211>  141
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: AAV2 ITR for RHA (AAV.323)

<400>  107
aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg ctcactgagg       60

ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc      120

gagcgcgcag ctgcctgcag g                                                141


<210>  108
<211>  4435
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor template, HBB Locus LHA to RHA  (AAV.304)

<400>  108
cttgctttga caattttggt ctttcagaat actataaata taacctatat tataatttca       60

taaagtctgt gcattttctt tgacccagga tatttgcaaa agacatattc aaacttccgc      120

agaacacttt atttcacata tacatgcctc ttatatcagg gatgtgaaac agggtcttga      180

aaactgtcta aatctaaaac aatgctaatg caggtttaaa tttaataaaa taaaatccaa      240

aatctaacag ccaagtcaaa tctgcatgtt ttaacattta aaatatttta aagacgtctt      300

ttcccaggat tcaacatgtg aaatcttttc tcagggatac acgtgtgcct agatcctcat      360

tgctttagtt ttttacagag gaatgaatat aaaaagaaaa tacttaaatt ttatccctct      420

tacctctata atcatacata ggcataattt tttaacctag gctccagata gccatagaag      480

aaccaaacac tttctgcgtg tgtgagaata atcagagtga gattttttca caagtacctg      540

atgagggttg agacaggtag aaaaagtgag agatctctat ttatttagca ataatagaga      600

aagcatttaa gagaataaag caatggaaat aagaaatttg taaatttcct tctgataact      660

agaaatagag gatccagttt cttttggtta acctaaattt tatttcattt tattgtttta      720

ttttatttta ttttatttta ttttgtgtaa tcgtagtttc agagtgttag agctgaaagg      780

aagaagtagg agaaacatgc aaagtaaaag tataacactt tccttactaa accgacatgg      840

gtttccaggt aggggcagga ttcaggatga ctgacagggc ccttagggaa cactgagacc      900

ctacgctgac ctcataaatg cttgctacct ttgctgtttt aattacatct tttaatagca      960

ggaagcagaa ctctgcactt caaaagtttt tcctcacctg aggagttaat ttagtacaag     1020

gggaaaaagt acagggggat gggagaaagg cgatcacgtt gggaagctat agagaaagaa     1080

gagtaaattt tagtaaagga ggtttaaaca aacaaaatat aaagagaaat aggaacttga     1140

atcaaggaaa tgattttaaa acgcagtatt cttagtggac tagaggaaaa aaataatctg     1200

agccaagtag aagacctttt cccctcctac ccctactttc taagtcacag aggctttttg     1260

ttcccccaga cactcttgca gattagtcca ggcagaaaca gttagatgtc cccagttaac     1320

ctcctatttg acaccactga ttaccccatt gatagtcaca ctttgggttg taagtgactt     1380

tttatttatt tgtatttttg actgcattaa gaggtctcta gttttttatc tcttgtttcc     1440

caaaacctaa taagtaacta atgcacagag cacattgatt tgtatttatt ctatttttag     1500

acataattta ttagcatgca tgagcaaatt aagaaaaaca acaacaaatg aatgcatata     1560

tatgtatatg tatgtgtgta tatatacaca catatatata tatatttttt cttttcttac     1620

cagaaggttt taatccaaat aaggagaaga tatgcttaga accgaggtag agttttcatc     1680

cattctgtcc tgtaagtatt ttgcatattc tggagacgca ggaagagatc catctacata     1740

tcccaaagct gaattatggt agacaaaact cttccacttt tagtgcatca acttcttatt     1800

tgtgtaataa gaaaattggg aaaacgatct tcaatatgct taccaagctg tgattccaaa     1860

tattacgtaa atacacttgc aaaggaggat gtttttagta gcaatttgta ctgatggtat     1920

ggggccaaga gatatatctt agagggaggg ctgagggttt gaagtccaac tcctaagcca     1980

gtgccagaag agccaaggac aggtacggct gtcatcactt agacctcacc ctgtggagcc     2040

acaccctagg gttggccaat ctactcccag gagcagggag ggcaggagcc agggctgggc     2100

ataaaagtca gggcagagcc atctattgct tacatttgct tctgacacaa ctgtgttcac     2160

tagcaacctc aaacagacac catggtgcat ctgactcctg tcgagaagtc tgcagtcact     2220

gctctatggg ggaaagtgaa cgtggatgaa gttggtggtg aggccctggg caggttggta     2280

tcaaggttac aagacaggtt taaggagacc aatagaaact gggcatgtgg agacagagaa     2340

gactcttggg tttctgatag gcactgactc tctctgccta ttggtctatt ttcccaccct     2400

taggctgctg gtggtctacc cttggaccca gaggttcttt gagtcctttg gggatctgtc     2460

cactcctgat gctgttatgg gcaaccctaa ggtgaaggct catggcaaga aagtgctcgg     2520

tgcctttagt gatggcctgg ctcacctgga caacctcaag ggcacctttg ccacactgag     2580

tgagctgcac tgtgacaagc tgcacgtgga tcctgagaac ttcagggtga gtctatggga     2640

cgcttgatgt tttctttccc cttcttttct atggttaagt tcatgtcata ggaaggggat     2700

aagtaacagg gtacagttta gaatgggaaa cagacgaatg attgcatcag tgtggaagtc     2760

tcaggatcgt tttagtttct tttatttgct gttcataaca attgttttct tttgtttaat     2820

tcttgctttc tttttttttc ttctccgcaa tttttactat tatacttaat gccttaacat     2880

tgtgtataac aaaaggaaat atctctgaga tacattaagt aacttaaaaa aaaactttac     2940

acagtctgcc tagtacatta ctatttggaa tatatgtgtg cttatttgca tattcataat     3000

ctccctactt tattttcttt tatttttaat tgatacataa tcattataca tatttatggg     3060

ttaaagtgta atgttttaat atgtgtacac atattgacca aatcagggta attttgcatt     3120

tgtaatttta aaaaatgctt tcttctttta atatactttt ttgtttatct tatttctaat     3180

actttcccta atctctttct ttcagggcaa taatgataca atgtatcatg cctctttgca     3240

ccattctaaa gaataacagt gataatttct gggttaaggc aatagcaata tctctgcata     3300

taaatatttc tgcatataaa ttgtaactga tgtaagaggt ttcatattgc taatagcagc     3360

tacaatccag ctaccattct gcttttattt tatggttggg ataaggctgg attattctga     3420

gtccaagcta ggcccttttg ctaatcatgt tcatacctct tatcttcctc ccacagctcc     3480

tgggcaacgt gctggtctgt gtgctggccc atcactttgg caaagaattc accccaccag     3540

tgcaggctgc ctatcagaaa gtggtggctg gtgtggctaa tgccctggcc cacaagtatc     3600

actaagctcg ctttcttgct gtccaatttc tattaaaggt tcctttgttc cctaagtcca     3660

actactaaac tgggggatat tatgaagggc cttgagcatc tggattctgc ctaataaaaa     3720

acatttattt tcattgcaat gatgtattta aattatttct gaatatttta ctaaaaaggg     3780

aatgtgggag gtcagtgcat ttaaaacata aagaaatgaa gagctagttc aaaccttggg     3840

aaaatacact atatcttaaa ctccatgaaa gaaggtgagg ctgcaaacag ctaatgcaca     3900

ttggcaacag cccctgatgc atatgcctta ttcatccctc agaaaaggat tcaagtagag     3960

gcttgatttg gaggttaaag ttttgctatg ctgtatttta cattacttat tgttttagct     4020

gtcctcatga atgtcttttc actacccatt tgcttatcct gcatctctca gccttgactc     4080

cactcagttc tcttgcttag agataccacc tttcccctga agtgttcctt ccatgtttta     4140

cggcgagatg gtttctcctc gcctggccac tcagccttag ttgtctctgt tgtcttatag     4200

aggtctactt gaagaaggaa aaacaggggt catggtttga ctgtcctgtg agcccttctt     4260

ccctgcctcc cccactcaca gtgacccgga atctgcagtg ctagtctccc ggaactatca     4320

ctctttcaca gtctgctttg gaaggactgg gcttagtatg aaaagttagg actgagaaga     4380

atttgaaagg cggctttttg tagcttgata ttcactactg tcttattacc ctgtc          4435


<210>  109
<211>  7118
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor template, Full AAV  (AAV.304)

<400>  109
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc       60

gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc tgcggccgca cgcgtcttgc tttgacaatt ttggtctttc      180

agaatactat aaatataacc tatattataa tttcataaag tctgtgcatt ttctttgacc      240

caggatattt gcaaaagaca tattcaaact tccgcagaac actttatttc acatatacat      300

gcctcttata tcagggatgt gaaacagggt cttgaaaact gtctaaatct aaaacaatgc      360

taatgcaggt ttaaatttaa taaaataaaa tccaaaatct aacagccaag tcaaatctgc      420

atgttttaac atttaaaata ttttaaagac gtcttttccc aggattcaac atgtgaaatc      480

ttttctcagg gatacacgtg tgcctagatc ctcattgctt tagtttttta cagaggaatg      540

aatataaaaa gaaaatactt aaattttatc cctcttacct ctataatcat acataggcat      600

aattttttaa cctaggctcc agatagccat agaagaacca aacactttct gcgtgtgtga      660

gaataatcag agtgagattt tttcacaagt acctgatgag ggttgagaca ggtagaaaaa      720

gtgagagatc tctatttatt tagcaataat agagaaagca tttaagagaa taaagcaatg      780

gaaataagaa atttgtaaat ttccttctga taactagaaa tagaggatcc agtttctttt      840

ggttaaccta aattttattt cattttattg ttttatttta ttttatttta ttttattttg      900

tgtaatcgta gtttcagagt gttagagctg aaaggaagaa gtaggagaaa catgcaaagt      960

aaaagtataa cactttcctt actaaaccga catgggtttc caggtagggg caggattcag     1020

gatgactgac agggccctta gggaacactg agaccctacg ctgacctcat aaatgcttgc     1080

tacctttgct gttttaatta catcttttaa tagcaggaag cagaactctg cacttcaaaa     1140

gtttttcctc acctgaggag ttaatttagt acaaggggaa aaagtacagg gggatgggag     1200

aaaggcgatc acgttgggaa gctatagaga aagaagagta aattttagta aaggaggttt     1260

aaacaaacaa aatataaaga gaaataggaa cttgaatcaa ggaaatgatt ttaaaacgca     1320

gtattcttag tggactagag gaaaaaaata atctgagcca agtagaagac cttttcccct     1380

cctaccccta ctttctaagt cacagaggct ttttgttccc ccagacactc ttgcagatta     1440

gtccaggcag aaacagttag atgtccccag ttaacctcct atttgacacc actgattacc     1500

ccattgatag tcacactttg ggttgtaagt gactttttat ttatttgtat ttttgactgc     1560

attaagaggt ctctagtttt ttatctcttg tttcccaaaa cctaataagt aactaatgca     1620

cagagcacat tgatttgtat ttattctatt tttagacata atttattagc atgcatgagc     1680

aaattaagaa aaacaacaac aaatgaatgc atatatatgt atatgtatgt gtgtatatat     1740

acacacatat atatatatat tttttctttt cttaccagaa ggttttaatc caaataagga     1800

gaagatatgc ttagaaccga ggtagagttt tcatccattc tgtcctgtaa gtattttgca     1860

tattctggag acgcaggaag agatccatct acatatccca aagctgaatt atggtagaca     1920

aaactcttcc acttttagtg catcaacttc ttatttgtgt aataagaaaa ttgggaaaac     1980

gatcttcaat atgcttacca agctgtgatt ccaaatatta cgtaaataca cttgcaaagg     2040

aggatgtttt tagtagcaat ttgtactgat ggtatggggc caagagatat atcttagagg     2100

gagggctgag ggtttgaagt ccaactccta agccagtgcc agaagagcca aggacaggta     2160

cggctgtcat cacttagacc tcaccctgtg gagccacacc ctagggttgg ccaatctact     2220

cccaggagca gggagggcag gagccagggc tgggcataaa agtcagggca gagccatcta     2280

ttgcttacat ttgcttctga cacaactgtg ttcactagca acctcaaaca gacaccatgg     2340

tgcatctgac tcctgtcgag aagtctgcag tcactgctct atgggggaaa gtgaacgtgg     2400

atgaagttgg tggtgaggcc ctgggcaggt tggtatcaag gttacaagac aggtttaagg     2460

agaccaatag aaactgggca tgtggagaca gagaagactc ttgggtttct gataggcact     2520

gactctctct gcctattggt ctattttccc acccttaggc tgctggtggt ctacccttgg     2580

acccagaggt tctttgagtc ctttggggat ctgtccactc ctgatgctgt tatgggcaac     2640

cctaaggtga aggctcatgg caagaaagtg ctcggtgcct ttagtgatgg cctggctcac     2700

ctggacaacc tcaagggcac ctttgccaca ctgagtgagc tgcactgtga caagctgcac     2760

gtggatcctg agaacttcag ggtgagtcta tgggacgctt gatgttttct ttccccttct     2820

tttctatggt taagttcatg tcataggaag gggataagta acagggtaca gtttagaatg     2880

ggaaacagac gaatgattgc atcagtgtgg aagtctcagg atcgttttag tttcttttat     2940

ttgctgttca taacaattgt tttcttttgt ttaattcttg ctttcttttt ttttcttctc     3000

cgcaattttt actattatac ttaatgcctt aacattgtgt ataacaaaag gaaatatctc     3060

tgagatacat taagtaactt aaaaaaaaac tttacacagt ctgcctagta cattactatt     3120

tggaatatat gtgtgcttat ttgcatattc ataatctccc tactttattt tcttttattt     3180

ttaattgata cataatcatt atacatattt atgggttaaa gtgtaatgtt ttaatatgtg     3240

tacacatatt gaccaaatca gggtaatttt gcatttgtaa ttttaaaaaa tgctttcttc     3300

ttttaatata cttttttgtt tatcttattt ctaatacttt ccctaatctc tttctttcag     3360

ggcaataatg atacaatgta tcatgcctct ttgcaccatt ctaaagaata acagtgataa     3420

tttctgggtt aaggcaatag caatatctct gcatataaat atttctgcat ataaattgta     3480

actgatgtaa gaggtttcat attgctaata gcagctacaa tccagctacc attctgcttt     3540

tattttatgg ttgggataag gctggattat tctgagtcca agctaggccc ttttgctaat     3600

catgttcata cctcttatct tcctcccaca gctcctgggc aacgtgctgg tctgtgtgct     3660

ggcccatcac tttggcaaag aattcacccc accagtgcag gctgcctatc agaaagtggt     3720

ggctggtgtg gctaatgccc tggcccacaa gtatcactaa gctcgctttc ttgctgtcca     3780

atttctatta aaggttcctt tgttccctaa gtccaactac taaactgggg gatattatga     3840

agggccttga gcatctggat tctgcctaat aaaaaacatt tattttcatt gcaatgatgt     3900

atttaaatta tttctgaata ttttactaaa aagggaatgt gggaggtcag tgcatttaaa     3960

acataaagaa atgaagagct agttcaaacc ttgggaaaat acactatatc ttaaactcca     4020

tgaaagaagg tgaggctgca aacagctaat gcacattggc aacagcccct gatgcatatg     4080

ccttattcat ccctcagaaa aggattcaag tagaggcttg atttggaggt taaagttttg     4140

ctatgctgta ttttacatta cttattgttt tagctgtcct catgaatgtc ttttcactac     4200

ccatttgctt atcctgcatc tctcagcctt gactccactc agttctcttg cttagagata     4260

ccacctttcc cctgaagtgt tccttccatg ttttacggcg agatggtttc tcctcgcctg     4320

gccactcagc cttagttgtc tctgttgtct tatagaggtc tacttgaaga aggaaaaaca     4380

ggggtcatgg tttgactgtc ctgtgagccc ttcttccctg cctcccccac tcacagtgac     4440

ccggaatctg cagtgctagt ctcccggaac tatcactctt tcacagtctg ctttggaagg     4500

actgggctta gtatgaaaag ttaggactga gaagaatttg aaaggcggct ttttgtagct     4560

tgatattcac tactgtctta ttaccctgtc ggtaaccacg tgcggccgag gctgcagcgt     4620

cgtcctccct aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg     4680

ctcactgagg ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca     4740

gtgagcgagc gagcgcgcag ctgcctgcag gggcgcctga tgcggtattt tctccttacg     4800

catctgtgcg gtatttcaca ccgcatacgt caaagcaacc atagtacgcg ccctgtagcg     4860

gcgcattaag cgcggcgggt gtggtggtta cgcgcagcgt gaccgctaca cttgccagcg     4920

ccctagcgcc cgctcctttc gctttcttcc cttcctttct cgccacgttc gccggctttc     4980

cccgtcaagc tctaaatcgg gggctccctt tagggttccg atttagtgct ttacggcacc     5040

tcgaccccaa aaaacttgat ttgggtgatg gttcacgtag tgggccatcg ccctgataga     5100

cggtttttcg ccctttgacg ttggagtcca cgttctttaa tagtggactc ttgttccaaa     5160

ctggaacaac actcaaccct atctcgggct attcttttga tttataaggg attttgccga     5220

tttcggccta ttggttaaaa aatgagctga tttaacaaaa atttaacgcg aattttaaca     5280

aaatattaac gtttacaatt ttatggtgca ctctcagtac aatctgctct gatgccgcat     5340

agttaagcca gccccgacac ccgccaacac ccgctgacgc gccctgacgg gcttgtctgc     5400

tcccggcatc cgcttacaga caagctgtga ccgtctccgg gagctgcatg tgtcagaggt     5460

tttcaccgtc atcaccgaaa cgcgcgagac gaaagggcct cgtgatacgc ctatttttat     5520

aggttaatgt catgaacaat aaaactgtct gcttacataa acagtaatac aaggggtgtt     5580

atgagccata ttcaacggga aacgtcgagg ccgcgattaa attccaacat ggatgctgat     5640

ttatatgggt ataaatgggc tcgcgataat gtcgggcaat caggtgcgac aatctatcgc     5700

ttgtatggga agcccgatgc gccagagttg tttctgaaac atggcaaagg tagcgttgcc     5760

aatgatgtta cagatgagat ggtcagacta aactggctga cggaatttat gcctcttccg     5820

accatcaagc attttatccg tactcctgat gatgcatggt tactcaccac tgcgatcccc     5880

ggaaaaacag cattccaggt attagaagaa tatcctgatt caggtgaaaa tattgttgat     5940

gcgctggcag tgttcctgcg ccggttgcat tcgattcctg tttgtaattg tccttttaac     6000

agcgatcgcg tatttcgtct cgctcaggcg caatcacgaa tgaataacgg tttggttgat     6060

gcgagtgatt ttgatgacga gcgtaatggc tggcctgttg aacaagtctg gaaagaaatg     6120

cataaacttt tgccattctc accggattca gtcgtcactc atggtgattt ctcacttgat     6180

aaccttattt ttgacgaggg gaaattaata ggttgtattg atgttggacg agtcggaatc     6240

gcagaccgat accaggatct tgccatccta tggaactgcc tcggtgagtt ttctccttca     6300

ttacagaaac ggctttttca aaaatatggt attgataatc ctgatatgaa taaattgcag     6360

tttcatttga tgctcgatga gtttttctaa tctcatgacc aaaatccctt aacgtgagtt     6420

ttcgttccac tgagcgtcag accccgtaga aaagatcaaa ggatcttctt gagatccttt     6480

ttttctgcgc gtaatctgct gcttgcaaac aaaaaaacca ccgctaccag cggtggtttg     6540

tttgccggat caagagctac caactctttt tccgaaggta actggcttca gcagagcgca     6600

gataccaaat actgtccttc tagtgtagcc gtagttaggc caccacttca agaactctgt     6660

agcaccgcct acatacctcg ctctgctaat cctgttacca gtggctgctg ccagtggcga     6720

taagtcgtgt cttaccgggt tggactcaag acgatagtta ccggataagg cgcagcggtc     6780

gggctgaacg gggggttcgt gcacacagcc cagcttggag cgaacgacct acaccgaact     6840

gagataccta cagcgtgagc tatgagaaag cgccacgctt cccgaaggga gaaaggcgga     6900

caggtatccg gtaagcggca gggtcggaac aggagagcgc acgagggagc ttccaggggg     6960

aaacgcctgg tatctttata gtcctgtcgg gtttcgccac ctctgacttg agcgtcgatt     7020

tttgtgatgc tcgtcagggg ggcggagcct atggaaaaac gccagcaacg cggccttttt     7080

acggttcctg gccttttgct ggccttttgc tcacatgt                             7118


<210>  110
<211>  4435
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor template, HBB Locus LHA to RHA  (AAV.307)

<400>  110
cttgctttga caattttggt ctttcagaat actataaata taacctatat tataatttca       60

taaagtctgt gcattttctt tgacccagga tatttgcaaa agacatattc aaacttccgc      120

agaacacttt atttcacata tacatgcctc ttatatcagg gatgtgaaac agggtcttga      180

aaactgtcta aatctaaaac aatgctaatg caggtttaaa tttaataaaa taaaatccaa      240

aatctaacag ccaagtcaaa tctgcatgtt ttaacattta aaatatttta aagacgtctt      300

ttcccaggat tcaacatgtg aaatcttttc tcagggatac acgtgtgcct agatcctcat      360

tgctttagtt ttttacagag gaatgaatat aaaaagaaaa tacttaaatt ttatccctct      420

tacctctata atcatacata ggcataattt tttaacctag gctccagata gccatagaag      480

aaccaaacac tttctgcgtg tgtgagaata atcagagtga gattttttca caagtacctg      540

atgagggttg agacaggtag aaaaagtgag agatctctat ttatttagca ataatagaga      600

aagcatttaa gagaataaag caatggaaat aagaaatttg taaatttcct tctgataact      660

agaaatagag gatccagttt cttttggtta acctaaattt tatttcattt tattgtttta      720

ttttatttta ttttatttta ttttgtgtaa tcgtagtttc agagtgttag agctgaaagg      780

aagaagtagg agaaacatgc aaagtaaaag tataacactt tccttactaa accgacatgg      840

gtttccaggt aggggcagga ttcaggatga ctgacagggc ccttagggaa cactgagacc      900

ctacgctgac ctcataaatg cttgctacct ttgctgtttt aattacatct tttaatagca      960

ggaagcagaa ctctgcactt caaaagtttt tcctcacctg aggagttaat ttagtacaag     1020

gggaaaaagt acagggggat gggagaaagg cgatcacgtt gggaagctat agagaaagaa     1080

gagtaaattt tagtaaagga ggtttaaaca aacaaaatat aaagagaaat aggaacttga     1140

atcaaggaaa tgattttaaa acgcagtatt cttagtggac tagaggaaaa aaataatctg     1200

agccaagtag aagacctttt cccctcctac ccctactttc taagtcacag aggctttttg     1260

ttcccccaga cactcttgca gattagtcca ggcagaaaca gttagatgtc cccagttaac     1320

ctcctatttg acaccactga ttaccccatt gatagtcaca ctttgggttg taagtgactt     1380

tttatttatt tgtatttttg actgcattaa gaggtctcta gttttttatc tcttgtttcc     1440

caaaacctaa taagtaacta atgcacagag cacattgatt tgtatttatt ctatttttag     1500

acataattta ttagcatgca tgagcaaatt aagaaaaaca acaacaaatg aatgcatata     1560

tatgtatatg tatgtgtgta tatatacaca catatatata tatatttttt cttttcttac     1620

cagaaggttt taatccaaat aaggagaaga tatgcttaga accgaggtag agttttcatc     1680

cattctgtcc tgtaagtatt ttgcatattc tggagacgca ggaagagatc catctacata     1740

tcccaaagct gaattatggt agacaaaact cttccacttt tagtgcatca acttcttatt     1800

tgtgtaataa gaaaattggg aaaacgatct tcaatatgct taccaagctg tgattccaaa     1860

tattacgtaa atacacttgc aaaggaggat gtttttagta gcaatttgta ctgatggtat     1920

ggggccaaga gatatatctt agagggaggg ctgagggttt gaagtccaac tcctaagcca     1980

gtgccagaag agccaaggac aggtacggct gtcatcactt agacctcacc ctgtggagcc     2040

acaccctagg gttggccaat ctactcccag gagcagggag ggcaggagcc agggctgggc     2100

ataaaagtca gggcagagcc atctattgct tacatttgct tctgacacaa ctgtgttcac     2160

tagcaacctc aaacagacac catggtgcat ctgactcctg tcgaaaaatc cgctgtcacc     2220

gccctctggg gcaaggtgaa cgtggatgaa gttggtggtg aggccctggg caggttggta     2280

tcaaggttac aagacaggtt taaggagacc aatagaaact gggcatgtgg agacagagaa     2340

gactcttggg tttctgatag gcactgactc tctctgccta ttggtctatt ttcccaccct     2400

taggctgctg gtggtctacc cttggaccca gaggttcttt gagtcctttg gggatctgtc     2460

cactcctgat gctgttatgg gcaaccctaa ggtgaaggct catggcaaga aagtgctcgg     2520

tgcctttagt gatggcctgg ctcacctgga caacctcaag ggcacctttg ccacactgag     2580

tgagctgcac tgtgacaagc tgcacgtgga tcctgagaac ttcagggtga gtctatggga     2640

cgcttgatgt tttctttccc cttcttttct atggttaagt tcatgtcata ggaaggggat     2700

aagtaacagg gtacagttta gaatgggaaa cagacgaatg attgcatcag tgtggaagtc     2760

tcaggatcgt tttagtttct tttatttgct gttcataaca attgttttct tttgtttaat     2820

tcttgctttc tttttttttc ttctccgcaa tttttactat tatacttaat gccttaacat     2880

tgtgtataac aaaaggaaat atctctgaga tacattaagt aacttaaaaa aaaactttac     2940

acagtctgcc tagtacatta ctatttggaa tatatgtgtg cttatttgca tattcataat     3000

ctccctactt tattttcttt tatttttaat tgatacataa tcattataca tatttatggg     3060

ttaaagtgta atgttttaat atgtgtacac atattgacca aatcagggta attttgcatt     3120

tgtaatttta aaaaatgctt tcttctttta atatactttt ttgtttatct tatttctaat     3180

actttcccta atctctttct ttcagggcaa taatgataca atgtatcatg cctctttgca     3240

ccattctaaa gaataacagt gataatttct gggttaaggc aatagcaata tctctgcata     3300

taaatatttc tgcatataaa ttgtaactga tgtaagaggt ttcatattgc taatagcagc     3360

tacaatccag ctaccattct gcttttattt tatggttggg ataaggctgg attattctga     3420

gtccaagcta ggcccttttg ctaatcatgt tcatacctct tatcttcctc ccacagctcc     3480

tgggcaacgt gctggtctgt gtgctggccc atcactttgg caaagaattc accccaccag     3540

tgcaggctgc ctatcagaaa gtggtggctg gtgtggctaa tgccctggcc cacaagtatc     3600

actaagctcg ctttcttgct gtccaatttc tattaaaggt tcctttgttc cctaagtcca     3660

actactaaac tgggggatat tatgaagggc cttgagcatc tggattctgc ctaataaaaa     3720

acatttattt tcattgcaat gatgtattta aattatttct gaatatttta ctaaaaaggg     3780

aatgtgggag gtcagtgcat ttaaaacata aagaaatgaa gagctagttc aaaccttggg     3840

aaaatacact atatcttaaa ctccatgaaa gaaggtgagg ctgcaaacag ctaatgcaca     3900

ttggcaacag cccctgatgc atatgcctta ttcatccctc agaaaaggat tcaagtagag     3960

gcttgatttg gaggttaaag ttttgctatg ctgtatttta cattacttat tgttttagct     4020

gtcctcatga atgtcttttc actacccatt tgcttatcct gcatctctca gccttgactc     4080

cactcagttc tcttgcttag agataccacc tttcccctga agtgttcctt ccatgtttta     4140

cggcgagatg gtttctcctc gcctggccac tcagccttag ttgtctctgt tgtcttatag     4200

aggtctactt gaagaaggaa aaacaggggt catggtttga ctgtcctgtg agcccttctt     4260

ccctgcctcc cccactcaca gtgacccgga atctgcagtg ctagtctccc ggaactatca     4320

ctctttcaca gtctgctttg gaaggactgg gcttagtatg aaaagttagg actgagaaga     4380

atttgaaagg cggctttttg tagcttgata ttcactactg tcttattacc ctgtc          4435


<210>  111
<211>  7118
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor template, Full AAV  (AAV.307)

<400>  111
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc       60

gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc tgcggccgca cgcgtcttgc tttgacaatt ttggtctttc      180

agaatactat aaatataacc tatattataa tttcataaag tctgtgcatt ttctttgacc      240

caggatattt gcaaaagaca tattcaaact tccgcagaac actttatttc acatatacat      300

gcctcttata tcagggatgt gaaacagggt cttgaaaact gtctaaatct aaaacaatgc      360

taatgcaggt ttaaatttaa taaaataaaa tccaaaatct aacagccaag tcaaatctgc      420

atgttttaac atttaaaata ttttaaagac gtcttttccc aggattcaac atgtgaaatc      480

ttttctcagg gatacacgtg tgcctagatc ctcattgctt tagtttttta cagaggaatg      540

aatataaaaa gaaaatactt aaattttatc cctcttacct ctataatcat acataggcat      600

aattttttaa cctaggctcc agatagccat agaagaacca aacactttct gcgtgtgtga      660

gaataatcag agtgagattt tttcacaagt acctgatgag ggttgagaca ggtagaaaaa      720

gtgagagatc tctatttatt tagcaataat agagaaagca tttaagagaa taaagcaatg      780

gaaataagaa atttgtaaat ttccttctga taactagaaa tagaggatcc agtttctttt      840

ggttaaccta aattttattt cattttattg ttttatttta ttttatttta ttttattttg      900

tgtaatcgta gtttcagagt gttagagctg aaaggaagaa gtaggagaaa catgcaaagt      960

aaaagtataa cactttcctt actaaaccga catgggtttc caggtagggg caggattcag     1020

gatgactgac agggccctta gggaacactg agaccctacg ctgacctcat aaatgcttgc     1080

tacctttgct gttttaatta catcttttaa tagcaggaag cagaactctg cacttcaaaa     1140

gtttttcctc acctgaggag ttaatttagt acaaggggaa aaagtacagg gggatgggag     1200

aaaggcgatc acgttgggaa gctatagaga aagaagagta aattttagta aaggaggttt     1260

aaacaaacaa aatataaaga gaaataggaa cttgaatcaa ggaaatgatt ttaaaacgca     1320

gtattcttag tggactagag gaaaaaaata atctgagcca agtagaagac cttttcccct     1380

cctaccccta ctttctaagt cacagaggct ttttgttccc ccagacactc ttgcagatta     1440

gtccaggcag aaacagttag atgtccccag ttaacctcct atttgacacc actgattacc     1500

ccattgatag tcacactttg ggttgtaagt gactttttat ttatttgtat ttttgactgc     1560

attaagaggt ctctagtttt ttatctcttg tttcccaaaa cctaataagt aactaatgca     1620

cagagcacat tgatttgtat ttattctatt tttagacata atttattagc atgcatgagc     1680

aaattaagaa aaacaacaac aaatgaatgc atatatatgt atatgtatgt gtgtatatat     1740

acacacatat atatatatat tttttctttt cttaccagaa ggttttaatc caaataagga     1800

gaagatatgc ttagaaccga ggtagagttt tcatccattc tgtcctgtaa gtattttgca     1860

tattctggag acgcaggaag agatccatct acatatccca aagctgaatt atggtagaca     1920

aaactcttcc acttttagtg catcaacttc ttatttgtgt aataagaaaa ttgggaaaac     1980

gatcttcaat atgcttacca agctgtgatt ccaaatatta cgtaaataca cttgcaaagg     2040

aggatgtttt tagtagcaat ttgtactgat ggtatggggc caagagatat atcttagagg     2100

gagggctgag ggtttgaagt ccaactccta agccagtgcc agaagagcca aggacaggta     2160

cggctgtcat cacttagacc tcaccctgtg gagccacacc ctagggttgg ccaatctact     2220

cccaggagca gggagggcag gagccagggc tgggcataaa agtcagggca gagccatcta     2280

ttgcttacat ttgcttctga cacaactgtg ttcactagca acctcaaaca gacaccatgg     2340

tgcatctgac tcctgtcgaa aaatccgctg tcaccgccct ctggggcaag gtgaacgtgg     2400

atgaagttgg tggtgaggcc ctgggcaggt tggtatcaag gttacaagac aggtttaagg     2460

agaccaatag aaactgggca tgtggagaca gagaagactc ttgggtttct gataggcact     2520

gactctctct gcctattggt ctattttccc acccttaggc tgctggtggt ctacccttgg     2580

acccagaggt tctttgagtc ctttggggat ctgtccactc ctgatgctgt tatgggcaac     2640

cctaaggtga aggctcatgg caagaaagtg ctcggtgcct ttagtgatgg cctggctcac     2700

ctggacaacc tcaagggcac ctttgccaca ctgagtgagc tgcactgtga caagctgcac     2760

gtggatcctg agaacttcag ggtgagtcta tgggacgctt gatgttttct ttccccttct     2820

tttctatggt taagttcatg tcataggaag gggataagta acagggtaca gtttagaatg     2880

ggaaacagac gaatgattgc atcagtgtgg aagtctcagg atcgttttag tttcttttat     2940

ttgctgttca taacaattgt tttcttttgt ttaattcttg ctttcttttt ttttcttctc     3000

cgcaattttt actattatac ttaatgcctt aacattgtgt ataacaaaag gaaatatctc     3060

tgagatacat taagtaactt aaaaaaaaac tttacacagt ctgcctagta cattactatt     3120

tggaatatat gtgtgcttat ttgcatattc ataatctccc tactttattt tcttttattt     3180

ttaattgata cataatcatt atacatattt atgggttaaa gtgtaatgtt ttaatatgtg     3240

tacacatatt gaccaaatca gggtaatttt gcatttgtaa ttttaaaaaa tgctttcttc     3300

ttttaatata cttttttgtt tatcttattt ctaatacttt ccctaatctc tttctttcag     3360

ggcaataatg atacaatgta tcatgcctct ttgcaccatt ctaaagaata acagtgataa     3420

tttctgggtt aaggcaatag caatatctct gcatataaat atttctgcat ataaattgta     3480

actgatgtaa gaggtttcat attgctaata gcagctacaa tccagctacc attctgcttt     3540

tattttatgg ttgggataag gctggattat tctgagtcca agctaggccc ttttgctaat     3600

catgttcata cctcttatct tcctcccaca gctcctgggc aacgtgctgg tctgtgtgct     3660

ggcccatcac tttggcaaag aattcacccc accagtgcag gctgcctatc agaaagtggt     3720

ggctggtgtg gctaatgccc tggcccacaa gtatcactaa gctcgctttc ttgctgtcca     3780

atttctatta aaggttcctt tgttccctaa gtccaactac taaactgggg gatattatga     3840

agggccttga gcatctggat tctgcctaat aaaaaacatt tattttcatt gcaatgatgt     3900

atttaaatta tttctgaata ttttactaaa aagggaatgt gggaggtcag tgcatttaaa     3960

acataaagaa atgaagagct agttcaaacc ttgggaaaat acactatatc ttaaactcca     4020

tgaaagaagg tgaggctgca aacagctaat gcacattggc aacagcccct gatgcatatg     4080

ccttattcat ccctcagaaa aggattcaag tagaggcttg atttggaggt taaagttttg     4140

ctatgctgta ttttacatta cttattgttt tagctgtcct catgaatgtc ttttcactac     4200

ccatttgctt atcctgcatc tctcagcctt gactccactc agttctcttg cttagagata     4260

ccacctttcc cctgaagtgt tccttccatg ttttacggcg agatggtttc tcctcgcctg     4320

gccactcagc cttagttgtc tctgttgtct tatagaggtc tacttgaaga aggaaaaaca     4380

ggggtcatgg tttgactgtc ctgtgagccc ttcttccctg cctcccccac tcacagtgac     4440

ccggaatctg cagtgctagt ctcccggaac tatcactctt tcacagtctg ctttggaagg     4500

actgggctta gtatgaaaag ttaggactga gaagaatttg aaaggcggct ttttgtagct     4560

tgatattcac tactgtctta ttaccctgtc ggtaaccacg tgcggccgag gctgcagcgt     4620

cgtcctccct aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg     4680

ctcactgagg ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca     4740

gtgagcgagc gagcgcgcag ctgcctgcag gggcgcctga tgcggtattt tctccttacg     4800

catctgtgcg gtatttcaca ccgcatacgt caaagcaacc atagtacgcg ccctgtagcg     4860

gcgcattaag cgcggcgggt gtggtggtta cgcgcagcgt gaccgctaca cttgccagcg     4920

ccctagcgcc cgctcctttc gctttcttcc cttcctttct cgccacgttc gccggctttc     4980

cccgtcaagc tctaaatcgg gggctccctt tagggttccg atttagtgct ttacggcacc     5040

tcgaccccaa aaaacttgat ttgggtgatg gttcacgtag tgggccatcg ccctgataga     5100

cggtttttcg ccctttgacg ttggagtcca cgttctttaa tagtggactc ttgttccaaa     5160

ctggaacaac actcaaccct atctcgggct attcttttga tttataaggg attttgccga     5220

tttcggccta ttggttaaaa aatgagctga tttaacaaaa atttaacgcg aattttaaca     5280

aaatattaac gtttacaatt ttatggtgca ctctcagtac aatctgctct gatgccgcat     5340

agttaagcca gccccgacac ccgccaacac ccgctgacgc gccctgacgg gcttgtctgc     5400

tcccggcatc cgcttacaga caagctgtga ccgtctccgg gagctgcatg tgtcagaggt     5460

tttcaccgtc atcaccgaaa cgcgcgagac gaaagggcct cgtgatacgc ctatttttat     5520

aggttaatgt catgaacaat aaaactgtct gcttacataa acagtaatac aaggggtgtt     5580

atgagccata ttcaacggga aacgtcgagg ccgcgattaa attccaacat ggatgctgat     5640

ttatatgggt ataaatgggc tcgcgataat gtcgggcaat caggtgcgac aatctatcgc     5700

ttgtatggga agcccgatgc gccagagttg tttctgaaac atggcaaagg tagcgttgcc     5760

aatgatgtta cagatgagat ggtcagacta aactggctga cggaatttat gcctcttccg     5820

accatcaagc attttatccg tactcctgat gatgcatggt tactcaccac tgcgatcccc     5880

ggaaaaacag cattccaggt attagaagaa tatcctgatt caggtgaaaa tattgttgat     5940

gcgctggcag tgttcctgcg ccggttgcat tcgattcctg tttgtaattg tccttttaac     6000

agcgatcgcg tatttcgtct cgctcaggcg caatcacgaa tgaataacgg tttggttgat     6060

gcgagtgatt ttgatgacga gcgtaatggc tggcctgttg aacaagtctg gaaagaaatg     6120

cataaacttt tgccattctc accggattca gtcgtcactc atggtgattt ctcacttgat     6180

aaccttattt ttgacgaggg gaaattaata ggttgtattg atgttggacg agtcggaatc     6240

gcagaccgat accaggatct tgccatccta tggaactgcc tcggtgagtt ttctccttca     6300

ttacagaaac ggctttttca aaaatatggt attgataatc ctgatatgaa taaattgcag     6360

tttcatttga tgctcgatga gtttttctaa tctcatgacc aaaatccctt aacgtgagtt     6420

ttcgttccac tgagcgtcag accccgtaga aaagatcaaa ggatcttctt gagatccttt     6480

ttttctgcgc gtaatctgct gcttgcaaac aaaaaaacca ccgctaccag cggtggtttg     6540

tttgccggat caagagctac caactctttt tccgaaggta actggcttca gcagagcgca     6600

gataccaaat actgtccttc tagtgtagcc gtagttaggc caccacttca agaactctgt     6660

agcaccgcct acatacctcg ctctgctaat cctgttacca gtggctgctg ccagtggcga     6720

taagtcgtgt cttaccgggt tggactcaag acgatagtta ccggataagg cgcagcggtc     6780

gggctgaacg gggggttcgt gcacacagcc cagcttggag cgaacgacct acaccgaact     6840

gagataccta cagcgtgagc tatgagaaag cgccacgctt cccgaaggga gaaaggcgga     6900

caggtatccg gtaagcggca gggtcggaac aggagagcgc acgagggagc ttccaggggg     6960

aaacgcctgg tatctttata gtcctgtcgg gtttcgccac ctctgacttg agcgtcgatt     7020

tttgtgatgc tcgtcagggg ggcggagcct atggaaaaac gccagcaacg cggccttttt     7080

acggttcctg gccttttgct ggccttttgc tcacatgt                             7118


<210>  112
<211>  141
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Donor template, 5 ITR

<400>  112
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc       60

gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc t                                                141


<210>  113
<211>  48
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Wild-type HBB gene region


<220>
<221>  misc_feature
<222>  (2)..(2)
<223>  n is c or t

<400>  113
anctgactcc tgaggagaag tctgccgtta ctgccctgtg gggcaagg                    48


<210>  114
<211>  48
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Sickle HBB gene region


<220>
<221>  misc_feature
<222>  (2)..(2)
<223>  n is c or t

<400>  114
anctgactcc tgtggagaag tctgccgtta ctgccctgtg gggcaagg                    48


<210>  115
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: R02 gRNA

<400>  115
cttgccccac agggcagtaa                                                   20


<210>  116
<211>  48
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: AAV.307

<400>  116
atctgactcc tgtcgaaaaa tccgctgtca ccgccctctg gggcaagg                    48


<210>  117
<211>  48
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: AAV.304

<400>  117
atctgactcc tgtcgagaag tctgcagtca ctgctctatg ggggaaag                    48


<210>  118
<211>  48
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: Beta-thal HBB gene region


<220>
<221>  misc_feature
<222>  (2)..(2)
<223>  n is c or t

<400>  118
anctgactcc tgaggagaag tctgcagtta ctgccctgtg gggcaagg                    48


<210>  119
<211>  48
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: AAV.323

<400>  119
atctgactcc tgaagaaaaa tccgctgtca ctgccctttg gggcaagg                    48


<210>  120
<211>  51
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: HBB -9 INDEL

<400>  120
acctgactcc tgaggagaag tctgccctgt ggggcaaggt gaacgtggat g                51


<210>  121
<211>  60
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Synthetic: HBB Wild-type Reference

<400>  121
acctgactcc tgaggagaag tctgccgtta ctgccctgtg gggcaaggtg aacgtggatg       60


<210>  122
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic: polypeptide sequence encoded by the NGS and reference 
       reads

<400>  122

Ser Ala Val Thr Ala 
1               5   


