                         SEQUENCE LISTING

<110>  The Trustees of the University of Pennsylvania
 
<120>  COMPOSITIONS AND METHODS FOR TREATMENT OF ARGININOSUCCINIC 
       ACIDURIA

<130>  UPN-17-8287PCT

<150>  US 62/545,851
<151>  2017-08-15

<150>  US 62/653,630
<151>  2018-04-06

<160>  11    

<170>  PatentIn version 3.5

<210>  1
<211>  2933
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  vector genome of AAV.ALSco


<220>
<221>  repeat_region
<222>  (1)..(168)
<223>  5'ITR

<220>
<221>  enhancer
<222>  (211)..(310)
<223>  alpha mic/bik

<220>
<221>  enhancer
<222>  (317)..(416)
<223>  alpha mic/bik

<220>
<221>  promoter
<222>  (431)..(907)
<223>  TBG promoter

<220>
<221>  Intron
<222>  (939)..(1071)
<223>  SV40 misc intron (Promega)

<220>
<221>  CDS
<222>  (1092)..(2483)
<223>  engineered ASL coding sequence (ALSco)

<220>
<221>  polyA_signal
<222>  (2502)..(2716)
<223>  BGH polyA

<220>
<221>  mutation
<222>  (2742)..(2742)
<223>  T to A mutation

<220>
<221>  misc_feature
<222>  (2758)..(2803)
<223>  Additional AAV sequences

<220>
<221>  repeat_region
<222>  (2766)..(2933)
<223>  3'ITR

<400>  1
ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact      120

aggggttcct tgtagttaat gattaacccg ccatgctact tatctacgta gccatgctct      180

aggaagatcg gaattcgccc ttaagctagc aggttaattt ttaaaaagca gtcaaaagtc      240

caagtggccc ttggcagcat ttactctctc tgtttgctct ggttaataat ctcaggagca      300

caaacattcc agatccaggt taatttttaa aaagcagtca aaagtccaag tggcccttgg      360

cagcatttac tctctctgtt tgctctggtt aataatctca ggagcacaaa cattccagat      420

ccggcgcgcc agggctggaa gctacctttg acatcatttc ctctgcgaat gcatgtataa      480

tttctacaga acctattaga aaggatcacc cagcctctgc ttttgtacaa ctttccctta      540

aaaaactgcc aattccactg ctgtttggcc caatagtgag aactttttcc tgctgcctct      600

tggtgctttt gcctatggcc cctattctgc ctgctgaaga cactcttgcc agcatggact      660

taaacccctc cagctctgac aatcctcttt ctcttttgtt ttacatgaag ggtctggcag      720

ccaaagcaat cactcaaagt tcaaacctta tcattttttg ctttgttcct cttggccttg      780

gttttgtaca tcagctttga aaataccatc ccagggttaa tgctggggtt aatttataac      840

taagagtgct ctagttttgc aatacaggac atgctataaa aatggaaaga tgttgctttc      900

tgagagactg cagaagttgg tcgtgaggca ctgggcaggt aagtatcaag gttacaagac      960

aggtttaagg agaccaatag aaactgggct tgtcgagaca gagaagactc ttgcgtttct     1020

gataggcacc tattggtctt actgacatcc actttgcctt tctctccaca ggtgtccagg     1080

cggccgccac c atg gcc tct gag tct ggc aaa ctg tgg ggc ggc aga ttc      1130
             Met Ala Ser Glu Ser Gly Lys Leu Trp Gly Gly Arg Phe          
             1               5                   10                       

gtg gga gcc gtg gac ccc atc atg gaa aag ttc aac gcc tct atc gcc       1178
Val Gly Ala Val Asp Pro Ile Met Glu Lys Phe Asn Ala Ser Ile Ala           
    15                  20                  25                            

tac gac cgg cac ctg tgg gaa gtg gac gtg cag ggc agc aag gcc tac       1226
Tyr Asp Arg His Leu Trp Glu Val Asp Val Gln Gly Ser Lys Ala Tyr           
30                  35                  40                  45            

agc aga ggc ctg gaa aag gcc gga ctg ctg acc aag gcc gag atg gac       1274
Ser Arg Gly Leu Glu Lys Ala Gly Leu Leu Thr Lys Ala Glu Met Asp           
                50                  55                  60                

cag atc ctg cac ggc ctg gac aag gtg gcc gaa gag tgg gcc cag ggc       1322
Gln Ile Leu His Gly Leu Asp Lys Val Ala Glu Glu Trp Ala Gln Gly           
            65                  70                  75                    

acc ttc aag ctg aac agc aac gac gag gac atc cac acc gcc aac gag       1370
Thr Phe Lys Leu Asn Ser Asn Asp Glu Asp Ile His Thr Ala Asn Glu           
        80                  85                  90                        

cgg cgg ctg aaa gag ctg att gga gcc aca gcc ggc aag ctg cac acc       1418
Arg Arg Leu Lys Glu Leu Ile Gly Ala Thr Ala Gly Lys Leu His Thr           
    95                  100                 105                           

ggc aga tcc aga aac gac cag gtc gtg acc gac ctg cgg ctg tgg atg       1466
Gly Arg Ser Arg Asn Asp Gln Val Val Thr Asp Leu Arg Leu Trp Met           
110                 115                 120                 125           

aga cag acc tgc agc aca ctg agc ggc ctg ctg tgg gag ctg atc cgg       1514
Arg Gln Thr Cys Ser Thr Leu Ser Gly Leu Leu Trp Glu Leu Ile Arg           
                130                 135                 140               

acc atg gtg gat aga gcc gag gcc gag cgg gac gtg ctg ttt cct ggc       1562
Thr Met Val Asp Arg Ala Glu Ala Glu Arg Asp Val Leu Phe Pro Gly           
            145                 150                 155                   

tac acc cat ctg cag cgg gcc cag cct atc agg tgg tcc cac tgg att       1610
Tyr Thr His Leu Gln Arg Ala Gln Pro Ile Arg Trp Ser His Trp Ile           
        160                 165                 170                       

ctg agc cac gcc gtg gcc ctg acc aga gac tct gag aga ctg ctg gaa       1658
Leu Ser His Ala Val Ala Leu Thr Arg Asp Ser Glu Arg Leu Leu Glu           
    175                 180                 185                           

gtg cgg aag cgg atc aac gtg ctg cct ctg ggc tct ggc gct atc gcc       1706
Val Arg Lys Arg Ile Asn Val Leu Pro Leu Gly Ser Gly Ala Ile Ala           
190                 195                 200                 205           

gga aat ccc ctg gga gtg gac aga gag ctg ctg cgg gcc gag ctg aat       1754
Gly Asn Pro Leu Gly Val Asp Arg Glu Leu Leu Arg Ala Glu Leu Asn           
                210                 215                 220               

ttc ggc gcc atc acc ctg aac tcc atg gac gcc acc agc gag agg gac       1802
Phe Gly Ala Ile Thr Leu Asn Ser Met Asp Ala Thr Ser Glu Arg Asp           
            225                 230                 235                   

ttc gtg gcc gag ttc ctg ttc tgg gcc agc ctg tgc atg acc cac ctg       1850
Phe Val Ala Glu Phe Leu Phe Trp Ala Ser Leu Cys Met Thr His Leu           
        240                 245                 250                       

agc aga atg gcc gag gac ctg atc ctg tac tgc acc aaa gaa ttc agc       1898
Ser Arg Met Ala Glu Asp Leu Ile Leu Tyr Cys Thr Lys Glu Phe Ser           
    255                 260                 265                           

ttc gtg cag ctg agc gac gcc tac tcc aca ggc agc agc ctg atg ccc       1946
Phe Val Gln Leu Ser Asp Ala Tyr Ser Thr Gly Ser Ser Leu Met Pro           
270                 275                 280                 285           

cag aag aag aac ccc gac agc ctg gaa ctg atc cgg tcc aag gcc ggc       1994
Gln Lys Lys Asn Pro Asp Ser Leu Glu Leu Ile Arg Ser Lys Ala Gly           
                290                 295                 300               

aga gtg ttc ggc agg tgt gcc ggg ctg ctg atg acc ctg aag ggc ctg       2042
Arg Val Phe Gly Arg Cys Ala Gly Leu Leu Met Thr Leu Lys Gly Leu           
            305                 310                 315                   

cct agc acc tac aac aag gac ctg cag gag gac aaa gag gcc gtg ttc       2090
Pro Ser Thr Tyr Asn Lys Asp Leu Gln Glu Asp Lys Glu Ala Val Phe           
        320                 325                 330                       

gag gtg tcc gac acc atg tct gcc gtg ctg cag gtg gcc aca ggc gtg       2138
Glu Val Ser Asp Thr Met Ser Ala Val Leu Gln Val Ala Thr Gly Val           
    335                 340                 345                           

atc tct aca ctg cag atc cac cag gaa aac atg ggc cag gcc ctg agc       2186
Ile Ser Thr Leu Gln Ile His Gln Glu Asn Met Gly Gln Ala Leu Ser           
350                 355                 360                 365           

ccc gat atg ctg gcc aca gac ctg gcc tac tac ctc gtg cgg aag gga       2234
Pro Asp Met Leu Ala Thr Asp Leu Ala Tyr Tyr Leu Val Arg Lys Gly           
                370                 375                 380               

atg ccc ttc aga cag gcc cac gag gcc tct ggc aaa gcc gtg ttc atg       2282
Met Pro Phe Arg Gln Ala His Glu Ala Ser Gly Lys Ala Val Phe Met           
            385                 390                 395                   

gcc gag aca aag ggc gtg gca ctg aac cag ctg agc ctg cag gaa ctg       2330
Ala Glu Thr Lys Gly Val Ala Leu Asn Gln Leu Ser Leu Gln Glu Leu           
        400                 405                 410                       

cag acc atc agc ccc ctg ttc agc ggc gac gtg atc tgc gtg tgg gac       2378
Gln Thr Ile Ser Pro Leu Phe Ser Gly Asp Val Ile Cys Val Trp Asp           
    415                 420                 425                           

tac ggc cac agc gtg gaa cag tat ggc gcc ctg ggc ggc aca gcc aga       2426
Tyr Gly His Ser Val Glu Gln Tyr Gly Ala Leu Gly Gly Thr Ala Arg           
430                 435                 440                 445           

tcc tct gtg gac tgg cag atc aga cag gtg cgc gcc ctg ctg cag gcc       2474
Ser Ser Val Asp Trp Gln Ile Arg Gln Val Arg Ala Leu Leu Gln Ala           
                450                 455                 460               

cag cag gct tgataagcat gcggatctgc ctcgactgtg ccttctagtt               2523
Gln Gln Ala                                                               
                                                                          

gccagccatc tgttgtttgc ccctcccccg tgccttcctt gaccctggaa ggtgccactc     2583

ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca ttgtctgagt aggtgtcatt     2643

ctattctggg gggtggggtg gggcaggaca gcaaggggga ggattgggaa gacaatagca     2703

ggcatgctgg ggactcgagt taagggcgaa ttcccgataa ggatcttcct agagcatggc     2763

tacgtagata agtagcatgg cgggttaatc attaactaca aggaacccct agtgatggag     2823

ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc     2883

cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag                2933


<210>  2
<211>  464
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  2

Met Ala Ser Glu Ser Gly Lys Leu Trp Gly Gly Arg Phe Val Gly Ala 
1               5                   10                  15      


Val Asp Pro Ile Met Glu Lys Phe Asn Ala Ser Ile Ala Tyr Asp Arg 
            20                  25                  30          


His Leu Trp Glu Val Asp Val Gln Gly Ser Lys Ala Tyr Ser Arg Gly 
        35                  40                  45              


Leu Glu Lys Ala Gly Leu Leu Thr Lys Ala Glu Met Asp Gln Ile Leu 
    50                  55                  60                  


His Gly Leu Asp Lys Val Ala Glu Glu Trp Ala Gln Gly Thr Phe Lys 
65                  70                  75                  80  


Leu Asn Ser Asn Asp Glu Asp Ile His Thr Ala Asn Glu Arg Arg Leu 
                85                  90                  95      


Lys Glu Leu Ile Gly Ala Thr Ala Gly Lys Leu His Thr Gly Arg Ser 
            100                 105                 110         


Arg Asn Asp Gln Val Val Thr Asp Leu Arg Leu Trp Met Arg Gln Thr 
        115                 120                 125             


Cys Ser Thr Leu Ser Gly Leu Leu Trp Glu Leu Ile Arg Thr Met Val 
    130                 135                 140                 


Asp Arg Ala Glu Ala Glu Arg Asp Val Leu Phe Pro Gly Tyr Thr His 
145                 150                 155                 160 


Leu Gln Arg Ala Gln Pro Ile Arg Trp Ser His Trp Ile Leu Ser His 
                165                 170                 175     


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


Arg Ile Asn Val Leu Pro Leu Gly Ser Gly Ala Ile Ala Gly Asn Pro 
        195                 200                 205             


Leu Gly Val Asp Arg Glu Leu Leu Arg Ala Glu Leu Asn Phe Gly Ala 
    210                 215                 220                 


Ile Thr Leu Asn Ser Met Asp Ala Thr Ser Glu Arg Asp Phe Val Ala 
225                 230                 235                 240 


Glu Phe Leu Phe Trp Ala Ser Leu Cys Met Thr His Leu Ser Arg Met 
                245                 250                 255     


Ala Glu Asp Leu Ile Leu Tyr Cys Thr Lys Glu Phe Ser Phe Val Gln 
            260                 265                 270         


Leu Ser Asp Ala Tyr Ser Thr Gly Ser Ser Leu Met Pro Gln Lys Lys 
        275                 280                 285             


Asn Pro Asp Ser Leu Glu Leu Ile Arg Ser Lys Ala Gly Arg Val Phe 
    290                 295                 300                 


Gly Arg Cys Ala Gly Leu Leu Met Thr Leu Lys Gly Leu Pro Ser Thr 
305                 310                 315                 320 


Tyr Asn Lys Asp Leu Gln Glu Asp Lys Glu Ala Val Phe Glu Val Ser 
                325                 330                 335     


Asp Thr Met Ser Ala Val Leu Gln Val Ala Thr Gly Val Ile Ser Thr 
            340                 345                 350         


Leu Gln Ile His Gln Glu Asn Met Gly Gln Ala Leu Ser Pro Asp Met 
        355                 360                 365             


Leu Ala Thr Asp Leu Ala Tyr Tyr Leu Val Arg Lys Gly Met Pro Phe 
    370                 375                 380                 


Arg Gln Ala His Glu Ala Ser Gly Lys Ala Val Phe Met Ala Glu Thr 
385                 390                 395                 400 


Lys Gly Val Ala Leu Asn Gln Leu Ser Leu Gln Glu Leu Gln Thr Ile 
                405                 410                 415     


Ser Pro Leu Phe Ser Gly Asp Val Ile Cys Val Trp Asp Tyr Gly His 
            420                 425                 430         


Ser Val Glu Gln Tyr Gly Ala Leu Gly Gly Thr Ala Arg Ser Ser Val 
        435                 440                 445             


Asp Trp Gln Ile Arg Gln Val Arg Ala Leu Leu Gln Ala Gln Gln Ala 
    450                 455                 460                 


<210>  3
<211>  1395
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Engineered ASL coding sequence

<400>  3
atggcctctg agtctggcaa actgtggggc ggcagattcg tgggagccgt ggaccccatc       60

atggaaaagt tcaacgcctc tatcgcctac gaccggcacc tgtgggaagt ggacgtgcag      120

ggcagcaagg cctacagcag aggcctggaa aaggccggac tgctgaccaa ggccgagatg      180

gaccagatcc tgcacggcct ggacaaggtg gccgaagagt gggcccaggg caccttcaag      240

ctgaacagca acgacgagga catccacacc gccaacgagc ggcggctgaa agagctgatt      300

ggagccacag ccggcaagct gcacaccggc agatccagaa acgaccaggt cgtgaccgac      360

ctgcggctgt ggatgagaca gacctgcagc acactgagcg gcctgctgtg ggagctgatc      420

cggaccatgg tggatagagc cgaggccgag cgggacgtgc tgtttcctgg ctacacccat      480

ctgcagcggg cccagcctat caggtggtcc cactggattc tgagccacgc cgtggccctg      540

accagagact ctgagagact gctggaagtg cggaagcgga tcaacgtgct gcctctgggc      600

tctggcgcta tcgccggaaa tcccctggga gtggacagag agctgctgcg ggccgagctg      660

aatttcggcg ccatcaccct gaactccatg gacgccacca gcgagaggga cttcgtggcc      720

gagttcctgt tctgggccag cctgtgcatg acccacctga gcagaatggc cgaggacctg      780

atcctgtact gcaccaaaga attcagcttc gtgcagctga gcgacgccta ctccacaggc      840

agcagcctga tgccccagaa gaagaacccc gacagcctgg aactgatccg gtccaaggcc      900

ggcagagtgt tcggcaggtg tgccgggctg ctgatgaccc tgaagggcct gcctagcacc      960

tacaacaagg acctgcagga ggacaaagag gccgtgttcg aggtgtccga caccatgtct     1020

gccgtgctgc aggtggccac aggcgtgatc tctacactgc agatccacca ggaaaacatg     1080

ggccaggccc tgagccccga tatgctggcc acagacctgg cctactacct cgtgcggaag     1140

ggaatgccct tcagacaggc ccacgaggcc tctggcaaag ccgtgttcat ggccgagaca     1200

aagggcgtgg cactgaacca gctgagcctg caggaactgc agaccatcag ccccctgttc     1260

agcggcgacg tgatctgcgt gtgggactac ggccacagcg tggaacagta tggcgccctg     1320

ggcggcacag ccagatcctc tgtggactgg cagatcagac aggtgcgcgc cctgctgcag     1380

gcccagcagg cttga                                                      1395


<210>  4
<211>  444
<212>  PRT
<213>  Homo sapiens

<400>  4

Met Ala Ser Glu Ser Gly Lys Leu Trp Gly Gly Arg Phe Val Gly Ala 
1               5                   10                  15      


Val Asp Pro Ile Met Glu Lys Phe Asn Ala Ser Ile Ala Tyr Asp Arg 
            20                  25                  30          


His Leu Trp Glu Val Asp Val Gln Gly Ser Lys Ala Tyr Ser Arg Gly 
        35                  40                  45              


Leu Glu Lys Ala Gly Leu Leu Thr Lys Ala Glu Met Asp Gln Ile Leu 
    50                  55                  60                  


His Gly Leu Asp Lys Val Ala Glu Glu Trp Ala Gln Gly Thr Phe Lys 
65                  70                  75                  80  


Leu Asn Ser Asn Asp Glu Asp Ile His Thr Ala Asn Glu Arg Arg Leu 
                85                  90                  95      


Lys Glu Leu Ile Gly Ala Thr Ala Gly Lys Leu His Thr Gly Arg Ser 
            100                 105                 110         


Arg Asn Asp Gln Val Val Thr Asp Leu Arg Leu Trp Met Arg Gln Thr 
        115                 120                 125             


Cys Ser Thr Leu Ser Gly Leu Leu Trp Glu Leu Ile Arg Thr Met Val 
    130                 135                 140                 


Asp Arg Ala Glu Ala Glu Arg Asp Val Leu Phe Pro Gly Tyr Thr His 
145                 150                 155                 160 


Leu Gln Arg Ala Gln Pro Ile Arg Trp Ser His Trp Ile Leu Ser His 
                165                 170                 175     


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


Arg Ile Asn Val Leu Pro Leu Gly Ser Gly Ala Ile Ala Gly Asn Pro 
        195                 200                 205             


Leu Gly Val Asp Arg Glu Leu Leu Arg Ala Glu Leu Asn Phe Gly Ala 
    210                 215                 220                 


Ile Thr Leu Asn Ser Met Asp Ala Thr Ser Glu Arg Asp Phe Val Ala 
225                 230                 235                 240 


Glu Phe Leu Phe Trp Ala Ser Leu Cys Met Thr His Leu Ser Arg Met 
                245                 250                 255     


Ala Glu Asp Leu Ile Leu Tyr Cys Thr Lys Glu Phe Ser Phe Val Gln 
            260                 265                 270         


Leu Ser Asp Ala Tyr Ser Thr Gly Ser Ser Leu Met Pro Gln Lys Lys 
        275                 280                 285             


Asn Pro Asp Ser Leu Glu Leu Ile Arg Ser Lys Ala Gly Arg Val Phe 
    290                 295                 300                 


Gly Arg Glu Asp Lys Glu Ala Val Phe Glu Val Ser Asp Thr Met Ser 
305                 310                 315                 320 


Ala Val Leu Gln Val Ala Thr Gly Val Ile Ser Thr Leu Gln Ile His 
                325                 330                 335     


Gln Glu Asn Met Gly Gln Ala Leu Ser Pro Asp Met Leu Ala Thr Asp 
            340                 345                 350         


Leu Ala Tyr Tyr Leu Val Arg Lys Gly Met Pro Phe Arg Gln Ala His 
        355                 360                 365             


Glu Ala Ser Gly Lys Ala Val Phe Met Ala Glu Thr Lys Gly Val Ala 
    370                 375                 380                 


Leu Asn Gln Leu Ser Leu Gln Glu Leu Gln Thr Ile Ser Pro Leu Phe 
385                 390                 395                 400 


Ser Gly Asp Val Ile Cys Val Trp Asp Tyr Gly His Ser Val Glu Gln 
                405                 410                 415     


Tyr Gly Ala Leu Gly Gly Thr Ala Arg Ser Ser Val Asp Trp Gln Ile 
            420                 425                 430         


Arg Gln Val Arg Ala Leu Leu Gln Ala Gln Gln Ala 
        435                 440                 


<210>  5
<211>  438
<212>  PRT
<213>  Homo sapiens

<400>  5

Met Ala Ser Glu Ser Gly Lys Leu Trp Gly Gly Arg Phe Val Gly Ala 
1               5                   10                  15      


Val Asp Pro Ile Met Glu Lys Phe Asn Ala Ser Ile Ala Tyr Asp Arg 
            20                  25                  30          


His Leu Trp Glu Val Asp Val Gln Gly Ser Lys Ala Tyr Ser Arg Gly 
        35                  40                  45              


Leu Glu Lys Ala Gly Leu Leu Thr Lys Ala Glu Met Asp Gln Ile Leu 
    50                  55                  60                  


His Gly Leu Asp Lys Val Ala Glu Glu Trp Ala Gln Gly Thr Phe Lys 
65                  70                  75                  80  


Leu Asn Ser Asn Asp Glu Asp Ile His Thr Ala Asn Glu Arg Arg Leu 
                85                  90                  95      


Lys Glu Leu Ile Gly Ala Thr Ala Gly Lys Leu His Thr Gly Arg Ser 
            100                 105                 110         


Arg Asn Asp Gln Val Val Thr Asp Leu Arg Leu Trp Met Arg Gln Thr 
        115                 120                 125             


Cys Ser Thr Leu Ser Gly Leu Leu Trp Glu Leu Ile Arg Thr Met Val 
    130                 135                 140                 


Asp Arg Ala Glu Ala Glu Arg Asp Val Leu Phe Pro Gly Tyr Thr His 
145                 150                 155                 160 


Leu Gln Arg Ala Gln Pro Ile Arg Trp Ser His Trp Ile Leu Ser Gly 
                165                 170                 175     


Ala Ile Ala Gly Asn Pro Leu Gly Val Asp Arg Glu Leu Leu Arg Ala 
            180                 185                 190         


Glu Leu Asn Phe Gly Ala Ile Thr Leu Asn Ser Met Asp Ala Thr Ser 
        195                 200                 205             


Glu Arg Asp Phe Val Ala Glu Phe Leu Phe Trp Ala Ser Leu Cys Met 
    210                 215                 220                 


Thr His Leu Ser Arg Met Ala Glu Asp Leu Ile Leu Tyr Cys Thr Lys 
225                 230                 235                 240 


Glu Phe Ser Phe Val Gln Leu Ser Asp Ala Tyr Ser Thr Gly Ser Ser 
                245                 250                 255     


Leu Met Pro Gln Lys Lys Asn Pro Asp Ser Leu Glu Leu Ile Arg Ser 
            260                 265                 270         


Lys Ala Gly Arg Val Phe Gly Arg Cys Ala Gly Leu Leu Met Thr Leu 
        275                 280                 285             


Lys Gly Leu Pro Ser Thr Tyr Asn Lys Asp Leu Gln Glu Asp Lys Glu 
    290                 295                 300                 


Ala Val Phe Glu Val Ser Asp Thr Met Ser Ala Val Leu Gln Val Ala 
305                 310                 315                 320 


Thr Gly Val Ile Ser Thr Leu Gln Ile His Gln Glu Asn Met Gly Gln 
                325                 330                 335     


Ala Leu Ser Pro Asp Met Leu Ala Thr Asp Leu Ala Tyr Tyr Leu Val 
            340                 345                 350         


Arg Lys Gly Met Pro Phe Arg Gln Ala His Glu Ala Ser Gly Lys Ala 
        355                 360                 365             


Val Phe Met Ala Glu Thr Lys Gly Val Ala Leu Asn Gln Leu Ser Leu 
    370                 375                 380                 


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


Val Trp Asp Tyr Gly His Ser Val Glu Gln Tyr Gly Ala Leu Gly Gly 
                405                 410                 415     


Thr Ala Arg Ser Ser Val Asp Trp Gln Ile Arg Gln Val Arg Ala Leu 
            420                 425                 430         


Leu Gln Ala Gln Gln Ala 
        435             


<210>  6
<211>  1395
<212>  DNA
<213>  Homo sapiens

<400>  6
atggcctcgg agagtgggaa gctttggggt ggccggtttg tgggtgcagt ggaccccatc       60

atggagaagt tcaacgcgtc cattgcctac gaccggcacc tttgggaggt ggatgttcaa      120

ggcagcaaag cctacagcag gggcctggag aaggcagggc tcctcaccaa ggccgagatg      180

gaccagatac tccatggcct agacaaggtg gctgaggagt gggcccaggg caccttcaaa      240

ctgaactcca atgatgagga catccacaca gccaatgagc gccgcctgaa ggagctcatt      300

ggtgcaacgg cagggaagct gcacacggga cggagccgga atgaccaggt ggtcacagac      360

ctcaggctgt ggatgcggca gacctgctcc acgctctcgg gcctcctctg ggagctcatt      420

aggaccatgg tggatcgggc agaggcggaa cgtgatgttc tcttcccggg gtacacccat      480

ttgcagaggg cccagcccat ccgctggagc cactggattc tgagccacgc cgtggcactg      540

acccgagact ctgagcggct gctggaggtg cggaagcgga tcaatgtcct gcccctgggg      600

agtggggcca ttgcaggcaa tcccctgggt gtggaccgag agctgctccg agcagaactc      660

aactttgggg ccatcactct caacagcatg gatgccacta gtgagcggga ctttgtggcc      720

gagttcctgt tctgggcttc gctgtgcatg acccatctca gcaggatggc cgaggacctc      780

atcctctact gcaccaagga attcagcttc gtgcagctct cagatgccta cagcacggga      840

agcagcctga tgccccagaa gaaaaacccc gacagtttgg agctgatccg gagcaaggct      900

gggcgtgtgt ttgggcggtg tgccgggctc ctgatgaccc tcaagggact tcccagcacc      960

tacaacaaag acttacagga ggacaaggaa gctgtgtttg aagtgtcaga cactatgagt     1020

gccgtgctcc aggtggccac tggcgtcatc tctacgctgc agattcacca agagaacatg     1080

ggacaggctc tcagccccga catgctggcc actgaccttg cctattacct ggtccgcaaa     1140

gggatgccat tccgccaggc ccacgaggcc tccgggaaag ctgtgttcat ggccgagacc     1200

aagggggtcg ccctcaacca gctgtcactg caggagctgc agaccatcag ccccctgttc     1260

tcgggcgacg tgatctgcgt gtgggactac gggcacagtg tggagcagta tggtgccctg     1320

ggcggcactg cgcgctccag cgtcgactgg cagatccgcc aggtgcgggc gctactgcag     1380

gcacagcagg cctag                                                      1395


<210>  7
<211>  1335
<212>  DNA
<213>  Homo sapiens

<400>  7
atggcctcgg agagtgggaa gctttggggt ggccggtttg tgggtgcagt ggaccccatc       60

atggagaagt tcaacgcgtc cattgcctac gaccggcacc tttgggaggt ggatgttcaa      120

ggcagcaaag cctacagcag gggcctggag aaggcagggc tcctcaccaa ggccgagatg      180

gaccagatac tccatggcct agacaaggtg gctgaggagt gggcccaggg caccttcaaa      240

ctgaactcca atgatgagga catccacaca gccaatgagc gccgcctgaa ggagctcatt      300

ggtgcaacgg cagggaagct gcacacggga cggagccgga atgaccaggt ggtcacagac      360

ctcaggctgt ggatgcggca gacctgctcc acgctctcgg gcctcctctg ggagctcatt      420

aggaccatgg tggatcgggc agaggcggaa cgtgatgttc tcttcccggg gtacacccat      480

ttgcagaggg cccagcccat ccgctggagc cactggattc tgagccacgc cgtggcactg      540

acccgagact ctgagcggct gctggaggtg cggaagcgga tcaatgtcct gcccctgggg      600

agtggggcca ttgcaggcaa tcccctgggt gtggaccgag agctgctccg agcagaactc      660

aactttgggg ccatcactct caacagcatg gatgccacta gtgagcggga ctttgtggcc      720

gagttcctgt tctgggcttc gctgtgcatg acccatctca gcaggatggc cgaggacctc      780

atcctctact gcaccaagga attcagcttc gtgcagctct cagatgccta cagcacggga      840

agcagcctga tgccccagaa gaaaaacccc gacagtttgg agctgatccg gagcaaggct      900

gggcgtgtgt ttgggcggga ggacaaggaa gctgtgtttg aagtgtcaga cactatgagt      960

gccgtgctcc aggtggccac tggcgtcatc tctacgctgc agattcacca agagaacatg     1020

ggacaggctc tcagccccga catgctggcc actgaccttg cctattacct ggtccgcaaa     1080

gggatgccat tccgccaggc ccacgaggcc tccgggaaag ctgtgttcat ggccgagacc     1140

aagggggtcg ccctcaacca gctgtcactg caggagctgc agaccatcag ccccctgttc     1200

tcgggcgacg tgatctgcgt gtgggactac gggcacagtg tggagcagta tggtgccctg     1260

ggcggcactg cgcgctccag cgtcgactgg cagatccgcc aggtgcgggc gctactgcag     1320

gcacagcagg cctag                                                      1335


<210>  8
<211>  1317
<212>  DNA
<213>  Homo sapiens

<400>  8
atggcctcgg agagtgggaa gctttggggt ggccggtttg tgggtgcagt ggaccccatc       60

atggagaagt tcaacgcgtc cattgcctac gaccggcacc tttgggaggt ggatgttcaa      120

ggcagcaaag cctacagcag gggcctggag aaggcagggc tcctcaccaa ggccgagatg      180

gaccagatac tccatggcct agacaaggtg gctgaggagt gggcccaggg caccttcaaa      240

ctgaactcca atgatgagga catccacaca gccaatgagc gccgcctgaa ggagctcatt      300

ggtgcaacgg cagggaagct gcacacggga cggagccgga atgaccaggt ggtcacagac      360

ctcaggctgt ggatgcggca gacctgctcc acgctctcgg gcctcctctg ggagctcatt      420

aggaccatgg tggatcgggc agaggcggaa cgtgatgttc tcttcccggg gtacacccat      480

ttgcagaggg cccagcccat ccgctggagc cactggattc tgagtggggc cattgcaggc      540

aatcccctgg gtgtggaccg agagctgctc cgagcagaac tcaactttgg ggccatcact      600

ctcaacagca tggatgccac tagtgagcgg gactttgtgg ccgagttcct gttctgggct      660

tcgctgtgca tgacccatct cagcaggatg gccgaggacc tcatcctcta ctgcaccaag      720

gaattcagct tcgtgcagct ctcagatgcc tacagcacgg gaagcagcct gatgccccag      780

aagaaaaacc ccgacagttt ggagctgatc cggagcaagg ctgggcgtgt gtttgggcgg      840

tgtgccgggc tcctgatgac cctcaaggga cttcccagca cctacaacaa agacttacag      900

gaggacaagg aagctgtgtt tgaagtgtca gacactatga gtgccgtgct ccaggtggcc      960

actggcgtca tctctacgct gcagattcac caagagaaca tgggacaggc tctcagcccc     1020

gacatgctgg ccactgacct tgcctattac ctggtccgca aagggatgcc attccgccag     1080

gcccacgagg cctccgggaa agctgtgttc atggccgaga ccaagggggt cgccctcaac     1140

cagctgtcac tgcaggagct gcagaccatc agccccctgt tctcgggcga cgtgatctgc     1200

gtgtgggact acgggcacag tgtggagcag tatggtgccc tgggcggcac tgcgcgctcc     1260

agcgtcgact ggcagatccg ccaggtgcgg gcgctactgc aggcacagca ggcctag        1317


<210>  9
<211>  7617
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  synthetic construct


<220>
<221>  repeat_region
<222>  (1)..(168)
<223>  AAV ITR(1)

<220>
<221>  promoter
<222>  (187)..(435)
<223>  U6 promoter

<220>
<221>  misc_RNA
<222>  (436)..(456)
<223>  2G6

<220>
<221>  misc_feature
<222>  (461)..(533)
<223>  gRNA scaffold(hSACas9)

<220>
<221>  terminator
<222>  (533)..(539)
<223>  U6 terminator

<220>
<221>  misc_feature
<222>  (630)..(1379)
<223>  5'Arm

<220>
<221>  enhancer
<222>  (1380)..(1479)
<223>  alpha mic/bik

<220>
<221>  enhancer
<222>  (1486)..(1585)
<223>  alpha mic/bik

<220>
<221>  promoter
<222>  (1600)..(2076)
<223>  TBG promoter

<220>
<221>  Intron
<222>  (2108)..(2240)
<223>  SV40 misc intron (Promega)

<220>
<221>  CDS
<222>  (2261)..(3652)
<223>  ASLco

<220>
<221>  polyA_signal
<222>  (3671)..(3885)
<223>  BGH pA

<220>
<221>  misc_feature
<222>  (3886)..(4635)
<223>  3'Arm

<220>
<221>  repeat_region
<222>  (4644)..(4807)
<223>  AAV ITR

<220>
<221>  CDS
<222>  (5570)..(6427)
<223>  Amp-R

<220>
<221>  misc_feature
<222>  (6601)..(7189)
<223>  Origin

<400>  9
ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact      120

aggggttcct tgtagttaat gattaacccg ccatgctact tatctactta aggcggccgc      180

acgcgtgagg gcctatttcc catgattcct tcatatttgc atatacgata caaggctgtt      240

agagagataa ttggaattaa tttgactgta aacacaaaga tattagtaca aaatacgtga      300

cgtagaaagt aataatttct tgggtagttt gcagttttaa aattatgttt taaaatggac      360

tatcatatgc ttaccgtaac ttgaaagtat ttcgatttct tggctttata tatcttgtgg      420

aaaggacgaa acaccgccct aatgctggta ttacaagttt tagtactctg gaaacagaat      480

ctactaaaac aaggcaaaat gccgtgttta tctcgtcaac ttgttggcga gatttttttg      540

ttttagagct agaaatagca agttaaaata aggctagtcc gtttttagcg cgtgcgccaa      600

ttctgcagac aaatggctct agaggtacct catatagaac cggccaggag ggagggacct      660

ctctccgtgg ccccagtgac tccctagggt gtcgctgtcc tctcctctgg gccaggaatc      720

cctggcttgt cttcctattt agtgaaaggt gtgcaagata taggtctccc gtgggcttgg      780

ttggtttagc tggtaaatgg aatgatgaca gctattgggc ttcacctgta aggaatggat      840

ctcagagtca tagctctgaa ctcttaggga atggaggctg tagggaagca gatgcctgca      900

tgtgtggtcc cttctggtct tcgttagctg gcaactcacc tccttcctcg tagctcatca      960

ttccgattaa agatttaact cacttgagtt acgacggcct gatctgctta gctgctgggt     1020

catgcggagg gtcaggaaca agggctggac tttggagcca aacagatgtg atttgtacac     1080

cagggtcctt gacctcttag ttcctttgtg aagtaggggt gttggtgtcc acttcataaa     1140

aggatgtaat tgcagtacca tgtaattgca gcggcccatg cctctaaacc cagcacttgg     1200

gagacagagg caggaggagc tccataagtt caaacccagc ctggtctata gactgagttc     1260

caggacagcc agggctacac agagaacccc tgtcttgaaa aacaaacaaa gaaaaaaaaa     1320

aaaacaaaca aacccacact attaatcctc ctacatctgc ctccctaatg ctggtattaa     1380

ggttaatttt taaaaagcag tcaaaagtcc aagtggccct tggcagcatt tactctctct     1440

gtttgctctg gttaataatc tcaggagcac aaacattcca gatccaggtt aatttttaaa     1500

aagcagtcaa aagtccaagt ggcccttggc agcatttact ctctctgttt gctctggtta     1560

ataatctcag gagcacaaac attccagatc cggcgcgcca gggctggaag ctacctttga     1620

catcatttcc tctgcgaatg catgtataat ttctacagaa cctattagaa aggatcaccc     1680

agcctctgct tttgtacaac tttcccttaa aaaactgcca attccactgc tgtttggccc     1740

aatagtgaga actttttcct gctgcctctt ggtgcttttg cctatggccc ctattctgcc     1800

tgctgaagac actcttgcca gcatggactt aaacccctcc agctctgaca atcctctttc     1860

tcttttgttt tacatgaagg gtctggcagc caaagcaatc actcaaagtt caaaccttat     1920

cattttttgc tttgttcctc ttggccttgg ttttgtacat cagctttgaa aataccatcc     1980

cagggttaat gctggggtta atttataact aagagtgctc tagttttgca atacaggaca     2040

tgctataaaa atggaaagat gttgctttct gagagactgc agaagttggt cgtgaggcac     2100

tgggcaggta agtatcaagg ttacaagaca ggtttaagga gaccaataga aactgggctt     2160

gtcgagacag agaagactct tgcgtttctg ataggcacct attggtctta ctgacatcca     2220

ctttgccttt ctctccacag gtgtccaggc ggccgccacc atg gcc tct gag tct       2275
                                            Met Ala Ser Glu Ser           
                                            1               5             

ggc aaa ctg tgg ggc ggc aga ttc gtg gga gcc gtg gac ccc atc atg       2323
Gly Lys Leu Trp Gly Gly Arg Phe Val Gly Ala Val Asp Pro Ile Met           
                10                  15                  20                

gaa aag ttc aac gcc tct atc gcc tac gac cgg cac ctg tgg gaa gtg       2371
Glu Lys Phe Asn Ala Ser Ile Ala Tyr Asp Arg His Leu Trp Glu Val           
            25                  30                  35                    

gac gtg cag ggc agc aag gcc tac agc aga ggc ctg gaa aag gcc gga       2419
Asp Val Gln Gly Ser Lys Ala Tyr Ser Arg Gly Leu Glu Lys Ala Gly           
        40                  45                  50                        

ctg ctg acc aag gcc gag atg gac cag atc ctg cac ggc ctg gac aag       2467
Leu Leu Thr Lys Ala Glu Met Asp Gln Ile Leu His Gly Leu Asp Lys           
    55                  60                  65                            

gtg gcc gaa gag tgg gcc cag ggc acc ttc aag ctg aac agc aac gac       2515
Val Ala Glu Glu Trp Ala Gln Gly Thr Phe Lys Leu Asn Ser Asn Asp           
70                  75                  80                  85            

gag gac atc cac acc gcc aac gag cgg cgg ctg aaa gag ctg att gga       2563
Glu Asp Ile His Thr Ala Asn Glu Arg Arg Leu Lys Glu Leu Ile Gly           
                90                  95                  100               

gcc aca gcc ggc aag ctg cac acc ggc aga tcc aga aac gac cag gtc       2611
Ala Thr Ala Gly Lys Leu His Thr Gly Arg Ser Arg Asn Asp Gln Val           
            105                 110                 115                   

gtg acc gac ctg cgg ctg tgg atg aga cag acc tgc agc aca ctg agc       2659
Val Thr Asp Leu Arg Leu Trp Met Arg Gln Thr Cys Ser Thr Leu Ser           
        120                 125                 130                       

ggc ctg ctg tgg gag ctg atc cgg acc atg gtg gat aga gcc gag gcc       2707
Gly Leu Leu Trp Glu Leu Ile Arg Thr Met Val Asp Arg Ala Glu Ala           
    135                 140                 145                           

gag cgg gac gtg ctg ttt cct ggc tac acc cat ctg cag cgg gcc cag       2755
Glu Arg Asp Val Leu Phe Pro Gly Tyr Thr His Leu Gln Arg Ala Gln           
150                 155                 160                 165           

cct atc agg tgg tcc cac tgg att ctg agc cac gcc gtg gcc ctg acc       2803
Pro Ile Arg Trp Ser His Trp Ile Leu Ser His Ala Val Ala Leu Thr           
                170                 175                 180               

aga gac tct gag aga ctg ctg gaa gtg cgg aag cgg atc aac gtg ctg       2851
Arg Asp Ser Glu Arg Leu Leu Glu Val Arg Lys Arg Ile Asn Val Leu           
            185                 190                 195                   

cct ctg ggc tct ggc gct atc gcc gga aat ccc ctg gga gtg gac aga       2899
Pro Leu Gly Ser Gly Ala Ile Ala Gly Asn Pro Leu Gly Val Asp Arg           
        200                 205                 210                       

gag ctg ctg cgg gcc gag ctg aat ttc ggc gcc atc acc ctg aac tcc       2947
Glu Leu Leu Arg Ala Glu Leu Asn Phe Gly Ala Ile Thr Leu Asn Ser           
    215                 220                 225                           

atg gac gcc acc agc gag agg gac ttc gtg gcc gag ttc ctg ttc tgg       2995
Met Asp Ala Thr Ser Glu Arg Asp Phe Val Ala Glu Phe Leu Phe Trp           
230                 235                 240                 245           

gcc agc ctg tgc atg acc cac ctg agc aga atg gcc gag gac ctg atc       3043
Ala Ser Leu Cys Met Thr His Leu Ser Arg Met Ala Glu Asp Leu Ile           
                250                 255                 260               

ctg tac tgc acc aaa gaa ttc agc ttc gtg cag ctg agc gac gcc tac       3091
Leu Tyr Cys Thr Lys Glu Phe Ser Phe Val Gln Leu Ser Asp Ala Tyr           
            265                 270                 275                   

tcc aca ggc agc agc ctg atg ccc cag aag aag aac ccc gac agc ctg       3139
Ser Thr Gly Ser Ser Leu Met Pro Gln Lys Lys Asn Pro Asp Ser Leu           
        280                 285                 290                       

gaa ctg atc cgg tcc aag gcc ggc aga gtg ttc ggc agg tgt gcc ggg       3187
Glu Leu Ile Arg Ser Lys Ala Gly Arg Val Phe Gly Arg Cys Ala Gly           
    295                 300                 305                           

ctg ctg atg acc ctg aag ggc ctg cct agc acc tac aac aag gac ctg       3235
Leu Leu Met Thr Leu Lys Gly Leu Pro Ser Thr Tyr Asn Lys Asp Leu           
310                 315                 320                 325           

cag gag gac aaa gag gcc gtg ttc gag gtg tcc gac acc atg tct gcc       3283
Gln Glu Asp Lys Glu Ala Val Phe Glu Val Ser Asp Thr Met Ser Ala           
                330                 335                 340               

gtg ctg cag gtg gcc aca ggc gtg atc tct aca ctg cag atc cac cag       3331
Val Leu Gln Val Ala Thr Gly Val Ile Ser Thr Leu Gln Ile His Gln           
            345                 350                 355                   

gaa aac atg ggc cag gcc ctg agc ccc gat atg ctg gcc aca gac ctg       3379
Glu Asn Met Gly Gln Ala Leu Ser Pro Asp Met Leu Ala Thr Asp Leu           
        360                 365                 370                       

gcc tac tac ctc gtg cgg aag gga atg ccc ttc aga cag gcc cac gag       3427
Ala Tyr Tyr Leu Val Arg Lys Gly Met Pro Phe Arg Gln Ala His Glu           
    375                 380                 385                           

gcc tct ggc aaa gcc gtg ttc atg gcc gag aca aag ggc gtg gca ctg       3475
Ala Ser Gly Lys Ala Val Phe Met Ala Glu Thr Lys Gly Val Ala Leu           
390                 395                 400                 405           

aac cag ctg agc ctg cag gaa ctg cag acc atc agc ccc ctg ttc agc       3523
Asn Gln Leu Ser Leu Gln Glu Leu Gln Thr Ile Ser Pro Leu Phe Ser           
                410                 415                 420               

ggc gac gtg atc tgc gtg tgg gac tac ggc cac agc gtg gaa cag tat       3571
Gly Asp Val Ile Cys Val Trp Asp Tyr Gly His Ser Val Glu Gln Tyr           
            425                 430                 435                   

ggc gcc ctg ggc ggc aca gcc aga tcc tct gtg gac tgg cag atc aga       3619
Gly Ala Leu Gly Gly Thr Ala Arg Ser Ser Val Asp Trp Gln Ile Arg           
        440                 445                 450                       

cag gtg cgc gcc ctg ctg cag gcc cag cag gct tgataagcat gcggatctgc     3672
Gln Val Arg Ala Leu Leu Gln Ala Gln Gln Ala                               
    455                 460                                               

ctcgactgtg ccttctagtt gccagccatc tgttgtttgc ccctcccccg tgccttcctt     3732

gaccctggaa ggtgccactc ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca     3792

ttgtctgagt aggtgtcatt ctattctggg gggtggggtg gggcaggaca gcaaggggga     3852

ggattgggaa gacaatagca ggcatgctgg ggacaagtga gtaccactac acccagctaa     3912

cagtaacttt tccgatgctt ctcttgtgca tttaaactga atcttactca ttccactcgg     3972

cccttttccc cttctcccag gcttccagcg tgcagcaata ccctctccat ttgtattggt     4032

ccagcctgaa cctatctcca caagccaaaa cacatggctg gggttgtagc tcagtggtga     4092

aacaccagct tagaatctct cactaaggga ctgggctatg actctgtggt agaccacctg     4152

tgtctcacaa acaaggccct gggttaaatt ccaaatatag gaatgggtgg ggtcaagggg     4212

gagtgtgtgt ctggaagcct gctgatggaa ttagagctca gagttctgca ctcctggaac     4272

acagtggtct gggctgcaga tggcctcagc ttgcctgaag ccattctgtg ggttgatact     4332

aattgttctg gctgctgtcc tgcttattaa ggagttgtta ttaccaacaa accaggcaca     4392

gaggccgaaa atctggaaag gaaggcagtg gcaggatgct tcctgggcct tcccctgcag     4452

cctcctgact tgtttctcca tactgactgt ctggccctga cccacaggcc ccaggggccc     4512

aggggggaag ggtgttgaag gagatccttc gaaggtcagg tgtagatcct ctcacagagc     4572

tgggggtgat gctggaggct gcttctgcgg ttcagagtcc ttctggcggt tgagcacaga     4632

gggctcgagt agataagtag catggcgggt taatcattaa ctacaaggaa cccctagtga     4692

tggagttggc cactccctct ctgcgcgctc gctcgctcac tgaggccggg cgaccaaagg     4752

tcgcccgacg cccgggcttt gcccgggcgg cctcagtgag cgagcgagcg cgcagcctta     4812

attaacctaa ttcactggcc gtcgttttac aacgtcgtga ctgggaaaac cctggcgtta     4872

cccaacttaa tcgccttgca gcacatcccc ctttcgccag ctggcgtaat agcgaagagg     4932

cccgcaccga tcgcccttcc caacagttgc gcagcctgaa tggcgaatgg gacgcgccct     4992

gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg cagcgtgacc gctacacttg     5052

ccagcgccct agcgcccgct cctttcgctt tcttcccttc ctttctcgcc acgttcgccg     5112

gctttccccg tcaagctcta aatcgggggc tccctttagg gttccgattt agtgctttac     5172

ggcacctcga ccccaaaaaa cttgattagg gtgatggttc acgtagtggg ccatcgccct     5232

gatagacggt ttttcgccct ttgacgttgg agtccacgtt ctttaatagt ggactcttgt     5292

tccaaactgg aacaacactc aaccctatct cggtctattc ttttgattta taagggattt     5352

tgccgatttc ggcctattgg ttaaaaaatg agctgattta acaaaaattt aacgcgaatt     5412

ttaacaaaat attaacgctt acaatttagg tggcactttt cggggaaatg tgcgcggaac     5472

ccctatttgt ttatttttct aaatacattc aaatatgtat ccgctcatga gacaataacc     5532

ctgataaatg cttcaataat attgaaaaag gaagagt atg agt att caa cat ttc      5587
                                         Met Ser Ile Gln His Phe          
                                         465                 470          

cgt gtc gcc ctt att ccc ttt ttt gcg gca ttt tgc ctt cct gtt ttt       5635
Arg Val Ala Leu Ile Pro Phe Phe Ala Ala Phe Cys Leu Pro Val Phe           
                475                 480                 485               

gct cac cca gaa acg ctg gtg aaa gta aaa gat gct gaa gat cag ttg       5683
Ala His Pro Glu Thr Leu Val Lys Val Lys Asp Ala Glu Asp Gln Leu           
            490                 495                 500                   

ggt gca cga gtg ggt tac atc gaa ctg gat ctc aac agc ggt aag atc       5731
Gly Ala Arg Val Gly Tyr Ile Glu Leu Asp Leu Asn Ser Gly Lys Ile           
        505                 510                 515                       

ctt gag agt ttt cgc ccc gaa gaa cgt ttt cca atg atg agc act ttt       5779
Leu Glu Ser Phe Arg Pro Glu Glu Arg Phe Pro Met Met Ser Thr Phe           
    520                 525                 530                           

aaa gtt ctg cta tgt ggc gcg gta tta tcc cgt att gac gcc ggg caa       5827
Lys Val Leu Leu Cys Gly Ala Val Leu Ser Arg Ile Asp Ala Gly Gln           
535                 540                 545                 550           

gag caa ctc ggt cgc cgc ata cac tat tct cag aat gac ttg gtt gag       5875
Glu Gln Leu Gly Arg Arg Ile His Tyr Ser Gln Asn Asp Leu Val Glu           
                555                 560                 565               

tac tca cca gtc aca gaa aag cat ctt acg gat ggc atg aca gta aga       5923
Tyr Ser Pro Val Thr Glu Lys His Leu Thr Asp Gly Met Thr Val Arg           
            570                 575                 580                   

gaa tta tgc agt gct gcc ata acc atg agt gat aac act gcg gcc aac       5971
Glu Leu Cys Ser Ala Ala Ile Thr Met Ser Asp Asn Thr Ala Ala Asn           
        585                 590                 595                       

tta ctt ctg aca acg atc gga gga ccg aag gag cta acc gct ttt ttg       6019
Leu Leu Leu Thr Thr Ile Gly Gly Pro Lys Glu Leu Thr Ala Phe Leu           
    600                 605                 610                           

cac aac atg ggg gat cat gta act cgc ctt gat cgt tgg gaa ccg gag       6067
His Asn Met Gly Asp His Val Thr Arg Leu Asp Arg Trp Glu Pro Glu           
615                 620                 625                 630           

ctg aat gaa gcc ata cca aac gac gag cgt gac acc acg atg cct gta       6115
Leu Asn Glu Ala Ile Pro Asn Asp Glu Arg Asp Thr Thr Met Pro Val           
                635                 640                 645               

gca atg gca aca acg ttg cgc aaa cta tta act ggc gaa cta ctt act       6163
Ala Met Ala Thr Thr Leu Arg Lys Leu Leu Thr Gly Glu Leu Leu Thr           
            650                 655                 660                   

cta gct tcc cgg caa caa tta ata gac tgg atg gag gcg gat aaa gtt       6211
Leu Ala Ser Arg Gln Gln Leu Ile Asp Trp Met Glu Ala Asp Lys Val           
        665                 670                 675                       

gca gga cca ctt ctg cgc tcg gcc ctt ccg gct ggc tgg ttt att gct       6259
Ala Gly Pro Leu Leu Arg Ser Ala Leu Pro Ala Gly Trp Phe Ile Ala           
    680                 685                 690                           

gat aaa tct gga gcc ggt gag cgt ggg tct cgc ggt atc att gca gca       6307
Asp Lys Ser Gly Ala Gly Glu Arg Gly Ser Arg Gly Ile Ile Ala Ala           
695                 700                 705                 710           

ctg ggg cca gat ggt aag ccc tcc cgt atc gta gtt atc tac acg acg       6355
Leu Gly Pro Asp Gly Lys Pro Ser Arg Ile Val Val Ile Tyr Thr Thr           
                715                 720                 725               

ggg agt cag gca act atg gat gaa cga aat aga cag atc gct gag ata       6403
Gly Ser Gln Ala Thr Met Asp Glu Arg Asn Arg Gln Ile Ala Glu Ile           
            730                 735                 740                   

ggt gcc tca ctg att aag cat tgg taactgtcag accaagttta ctcatatata      6457
Gly Ala Ser Leu Ile Lys His Trp                                           
        745                 750                                           

ctttagattg atttaaaact tcatttttaa tttaaaagga tctaggtgaa gatccttttt     6517

gataatctca tgaccaaaat cccttaacgt gagttttcgt tccactgagc gtcagacccc     6577

gtagaaaaga tcaaaggatc ttcttgagat cctttttttc tgcgcgtaat ctgctgcttg     6637

caaacaaaaa aaccaccgct accagcggtg gtttgtttgc cggatcaaga gctaccaact     6697

ctttttccga aggtaactgg cttcagcaga gcgcagatac caaatactgt tcttctagtg     6757

tagccgtagt taggccacca cttcaagaac tctgtagcac cgcctacata cctcgctctg     6817

ctaatcctgt taccagtggc tgctgccagt ggcgataagt cgtgtcttac cgggttggac     6877

tcaagacgat agttaccgga taaggcgcag cggtcgggct gaacgggggg ttcgtgcaca     6937

cagcccagct tggagcgaac gacctacacc gaactgagat acctacagcg tgagctatga     6997

gaaagcgcca cgcttcccga agggagaaag gcggacaggt atccggtaag cggcagggtc     7057

ggaacaggag agcgcacgag ggagcttcca gggggaaacg cctggtatct ttatagtcct     7117

gtcgggtttc gccacctctg acttgagcgt cgatttttgt gatgctcgtc aggggggcgg     7177

agcctatgga aaaacgccag caacgcggcc tttttacggt tcctggcctt ttgctggcct     7237

tttgctcaca tgttctttcc tgcgttatcc cctgattctg tggataaccg tattaccgcc     7297

tttgagtgag ctgataccgc tcgccgcagc cgaacgaccg agcgcagcga gtcagtgagc     7357

gaggaagcgg aagagcgccc aatacgcaaa ccgcctctcc ccgcgcgttg gccgattcat     7417

taatgcagct ggcacgacag gtttcccgac tggaaagcgg gcagtgagcg caacgcaatt     7477

aatgtgagtt agctcactca ttaggcaccc caggctttac actttatgct tccggctcgt     7537

atgttgtgtg gaattgtgag cggataacaa tttcacacag gaaacagcta tgaccatgat     7597

tacgccagat ttaattaagg                                                 7617


<210>  10
<211>  464
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  10

Met Ala Ser Glu Ser Gly Lys Leu Trp Gly Gly Arg Phe Val Gly Ala 
1               5                   10                  15      


Val Asp Pro Ile Met Glu Lys Phe Asn Ala Ser Ile Ala Tyr Asp Arg 
            20                  25                  30          


His Leu Trp Glu Val Asp Val Gln Gly Ser Lys Ala Tyr Ser Arg Gly 
        35                  40                  45              


Leu Glu Lys Ala Gly Leu Leu Thr Lys Ala Glu Met Asp Gln Ile Leu 
    50                  55                  60                  


His Gly Leu Asp Lys Val Ala Glu Glu Trp Ala Gln Gly Thr Phe Lys 
65                  70                  75                  80  


Leu Asn Ser Asn Asp Glu Asp Ile His Thr Ala Asn Glu Arg Arg Leu 
                85                  90                  95      


Lys Glu Leu Ile Gly Ala Thr Ala Gly Lys Leu His Thr Gly Arg Ser 
            100                 105                 110         


Arg Asn Asp Gln Val Val Thr Asp Leu Arg Leu Trp Met Arg Gln Thr 
        115                 120                 125             


Cys Ser Thr Leu Ser Gly Leu Leu Trp Glu Leu Ile Arg Thr Met Val 
    130                 135                 140                 


Asp Arg Ala Glu Ala Glu Arg Asp Val Leu Phe Pro Gly Tyr Thr His 
145                 150                 155                 160 


Leu Gln Arg Ala Gln Pro Ile Arg Trp Ser His Trp Ile Leu Ser His 
                165                 170                 175     


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


Arg Ile Asn Val Leu Pro Leu Gly Ser Gly Ala Ile Ala Gly Asn Pro 
        195                 200                 205             


Leu Gly Val Asp Arg Glu Leu Leu Arg Ala Glu Leu Asn Phe Gly Ala 
    210                 215                 220                 


Ile Thr Leu Asn Ser Met Asp Ala Thr Ser Glu Arg Asp Phe Val Ala 
225                 230                 235                 240 


Glu Phe Leu Phe Trp Ala Ser Leu Cys Met Thr His Leu Ser Arg Met 
                245                 250                 255     


Ala Glu Asp Leu Ile Leu Tyr Cys Thr Lys Glu Phe Ser Phe Val Gln 
            260                 265                 270         


Leu Ser Asp Ala Tyr Ser Thr Gly Ser Ser Leu Met Pro Gln Lys Lys 
        275                 280                 285             


Asn Pro Asp Ser Leu Glu Leu Ile Arg Ser Lys Ala Gly Arg Val Phe 
    290                 295                 300                 


Gly Arg Cys Ala Gly Leu Leu Met Thr Leu Lys Gly Leu Pro Ser Thr 
305                 310                 315                 320 


Tyr Asn Lys Asp Leu Gln Glu Asp Lys Glu Ala Val Phe Glu Val Ser 
                325                 330                 335     


Asp Thr Met Ser Ala Val Leu Gln Val Ala Thr Gly Val Ile Ser Thr 
            340                 345                 350         


Leu Gln Ile His Gln Glu Asn Met Gly Gln Ala Leu Ser Pro Asp Met 
        355                 360                 365             


Leu Ala Thr Asp Leu Ala Tyr Tyr Leu Val Arg Lys Gly Met Pro Phe 
    370                 375                 380                 


Arg Gln Ala His Glu Ala Ser Gly Lys Ala Val Phe Met Ala Glu Thr 
385                 390                 395                 400 


Lys Gly Val Ala Leu Asn Gln Leu Ser Leu Gln Glu Leu Gln Thr Ile 
                405                 410                 415     


Ser Pro Leu Phe Ser Gly Asp Val Ile Cys Val Trp Asp Tyr Gly His 
            420                 425                 430         


Ser Val Glu Gln Tyr Gly Ala Leu Gly Gly Thr Ala Arg Ser Ser Val 
        435                 440                 445             


Asp Trp Gln Ile Arg Gln Val Arg Ala Leu Leu Gln Ala Gln Gln Ala 
    450                 455                 460                 


<210>  11
<211>  286
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic Construct

<400>  11

Met Ser Ile Gln His Phe Arg Val Ala Leu Ile Pro Phe Phe Ala Ala 
1               5                   10                  15      


Phe Cys Leu Pro Val Phe Ala His Pro Glu Thr Leu Val Lys Val Lys 
            20                  25                  30          


Asp Ala Glu Asp Gln Leu Gly Ala Arg Val Gly Tyr Ile Glu Leu Asp 
        35                  40                  45              


Leu Asn Ser Gly Lys Ile Leu Glu Ser Phe Arg Pro Glu Glu Arg Phe 
    50                  55                  60                  


Pro Met Met Ser Thr Phe Lys Val Leu Leu Cys Gly Ala Val Leu Ser 
65                  70                  75                  80  


Arg Ile Asp Ala Gly Gln Glu Gln Leu Gly Arg Arg Ile His Tyr Ser 
                85                  90                  95      


Gln Asn Asp Leu Val Glu Tyr Ser Pro Val Thr Glu Lys His Leu Thr 
            100                 105                 110         


Asp Gly Met Thr Val Arg Glu Leu Cys Ser Ala Ala Ile Thr Met Ser 
        115                 120                 125             


Asp Asn Thr Ala Ala Asn Leu Leu Leu Thr Thr Ile Gly Gly Pro Lys 
    130                 135                 140                 


Glu Leu Thr Ala Phe Leu His Asn Met Gly Asp His Val Thr Arg Leu 
145                 150                 155                 160 


Asp Arg Trp Glu Pro Glu Leu Asn Glu Ala Ile Pro Asn Asp Glu Arg 
                165                 170                 175     


Asp Thr Thr Met Pro Val Ala Met Ala Thr Thr Leu Arg Lys Leu Leu 
            180                 185                 190         


Thr Gly Glu Leu Leu Thr Leu Ala Ser Arg Gln Gln Leu Ile Asp Trp 
        195                 200                 205             


Met Glu Ala Asp Lys Val Ala Gly Pro Leu Leu Arg Ser Ala Leu Pro 
    210                 215                 220                 


Ala Gly Trp Phe Ile Ala Asp Lys Ser Gly Ala Gly Glu Arg Gly Ser 
225                 230                 235                 240 


Arg Gly Ile Ile Ala Ala Leu Gly Pro Asp Gly Lys Pro Ser Arg Ile 
                245                 250                 255     


Val Val Ile Tyr Thr Thr Gly Ser Gln Ala Thr Met Asp Glu Arg Asn 
            260                 265                 270         


Arg Gln Ile Ala Glu Ile Gly Ala Ser Leu Ile Lys His Trp 
        275                 280                 285     


