                         SEQUENCE LISTING

<110>  HOMOLOGY MEDICINES, INC.
 
<120>  METHODS OF TREATING PHENYLKETONURIA

<130>  713280: HMW-039PC

<160>  23    

<170>  PatentIn version 3.5

<210>  1
<211>  1359
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Silently altered PAH coding sequence

<400>  1
atgtccaccg ctgtgctgga gaaccctggg ctggggagga aactgtcaga cttcgggcag       60

gagacttcat acattgagga taactgtaac cagaatggcg ccatctctct gatcttcagc      120

ctgaaggagg aagtgggcgc cctggcaaag gtgctgcgcc tgtttgagga gaacgacgtg      180

aatctgaccc acatcgagtc ccggccttct agactgaaga aggacgagta cgagttcttt      240

acccacctgg ataagcggtc cctgccagcc ctgacaaaca tcatcaagat cctgaggcac      300

gacatcggag caaccgtgca cgagctgtct cgggacaaga agaaggatac cgtgccctgg      360

ttccctcgga caatccagga gctggataga tttgccaacc agatcctgtc ttacggagca      420

gagctggacg cagatcaccc tggcttcaag gacccagtgt atcgggcccg gagaaagcag      480

tttgccgata tcgcctacaa ttataggcac ggacagccaa tccctcgcgt ggagtatatg      540

gaggaggaga agaagacctg gggcacagtg ttcaagaccc tgaagagcct gtacaagaca      600

cacgcctgct acgagtataa ccacatcttc cccctgctgg agaagtattg tggctttcac      660

gaggacaata tccctcagct ggaggacgtg agccagttcc tgcagacctg cacaggcttt      720

aggctgaggc cagtggcagg actgctgagc tcccgggact tcctgggagg actggccttc      780

agagtgtttc actgcaccca gtacatcagg cacggctcca agccaatgta tacaccagag      840

cccgacatct gtcacgagct gctgggccac gtgcccctgt ttagcgatag atccttcgcc      900

cagttttccc aggagatcgg actggcatct ctgggagcac ctgacgagta catcgagaag      960

ctggccacca tctattggtt cacagtggag tttggcctgt gcaagcaggg cgatagcatc     1020

aaggcctacg gagcaggact gctgtctagc ttcggcgagc tgcagtattg tctgtccgag     1080

aagccaaagc tgctgcccct ggagctggag aagaccgcca tccagaacta caccgtgaca     1140

gagttccagc ccctgtacta tgtggccgag tcttttaacg atgccaagga gaaggtgaga     1200

aatttcgccg ccacaatccc taggcccttc agcgtgcggt acgaccctta tacccagagg     1260

atcgaggtgc tggataatac acagcagctg aagatcctgg ctgactcaat caatagcgaa     1320

atcggaatcc tgtgctccgc cctgcagaaa atcaaatga                            1359


<210>  2
<211>  192
<212>  DNA
<213>  Homo sapiens

<400>  2
ccctaaaatg ggcaaacatt gcaagcagca aacagcaaac acacagccct ccctgcctgc       60

tgaccttgga gctggggcag aggtcagaga cctctctggg cccatgccac ctccaacatc      120

cactcgaccc cttggaattt cggtggagag gagcagaggt tgtcctggcg tggtttaggt      180

agtgtgagag gg                                                          192


<210>  3
<211>  205
<212>  DNA
<213>  Homo sapiens

<400>  3
aatgactcct ttcggtaagt gcagtggaag ctgtacactg cccaggcaaa gcgtccgggc       60

agcgtaggcg ggcgactcag atcccagcca gtggacttag cccctgtttg ctcctccgat      120

aactggggtg accttggtta atattcacca gcagcctccc ccgttgcccc tctggatcca      180

ctgcttaaat acggacgagg acagg                                            205


<210>  4
<211>  93
<212>  DNA
<213>  Simian virus 40

<400>  4
ctctaaggta aatataaaat ttttaagtgt ataatgtgtt aaactactga ttctaattgt       60

ttctctcttt tagattccaa cctttggaac tga                                    93


<210>  5
<211>  398
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  pHMI-hPAH-TC-025 transcriptional regulatory region

<400>  5
ccctaaaatg ggcaaacatt gcaagcagca aacagcaaac acacagccct ccctgcctgc       60

tgaccttgga gctggggcag aggtcagaga cctctctggg cccatgccac ctccaacatc      120

cactcgaccc cttggaattt cggtggagag gagcagaggt tgtcctggcg tggtttaggt      180

agtgtgagag gggaatgact cctttcggta agtgcagtgg aagctgtaca ctgcccaggc      240

aaagcgtccg ggcagcgtag gcgggcgact cagatcccag ccagtggact tagcccctgt      300

ttgctcctcc gataactggg gtgaccttgg ttaatattca ccagcagcct cccccgttgc      360

ccctctggat ccactgctta aatacggacg aggacagg                              398


<210>  6
<211>  133
<212>  DNA
<213>  Simian virus 40

<400>  6
tgctttattt gtgaaatttg tgatgctatt gctttatttg taaccattat aagctgcaat       60

aaacaagtta acaacaacaa ttgcattcat tttatgtttc aggttcaggg ggaggtgtgg      120

gaggtttttt aaa                                                         133


<210>  7
<211>  2042
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  pHMI-hPAH-TC-025 transfer genome

<400>  7
ccctaaaatg ggcaaacatt gcaagcagca aacagcaaac acacagccct ccctgcctgc       60

tgaccttgga gctggggcag aggtcagaga cctctctggg cccatgccac ctccaacatc      120

cactcgaccc cttggaattt cggtggagag gagcagaggt tgtcctggcg tggtttaggt      180

agtgtgagag gggaatgact cctttcggta agtgcagtgg aagctgtaca ctgcccaggc      240

aaagcgtccg ggcagcgtag gcgggcgact cagatcccag ccagtggact tagcccctgt      300

ttgctcctcc gataactggg gtgaccttgg ttaatattca ccagcagcct cccccgttgc      360

ccctctggat ccactgctta aatacggacg aggacagggc cctgtctcct cagcttcagg      420

caccaccact gacctgggac agtgaatcct ctaaggtaaa tataaaattt ttaagtgtat      480

aatgtgttaa actactgatt ctaattgttt ctctctttta gattccaacc tttggaactg      540

accgccacca tgtccaccgc tgtgctggag aaccctgggc tggggaggaa actgtcagac      600

ttcgggcagg agacttcata cattgaggat aactgtaacc agaatggcgc catctctctg      660

atcttcagcc tgaaggagga agtgggcgcc ctggcaaagg tgctgcgcct gtttgaggag      720

aacgacgtga atctgaccca catcgagtcc cggccttcta gactgaagaa ggacgagtac      780

gagttcttta cccacctgga taagcggtcc ctgccagccc tgacaaacat catcaagatc      840

ctgaggcacg acatcggagc aaccgtgcac gagctgtctc gggacaagaa gaaggatacc      900

gtgccctggt tccctcggac aatccaggag ctggatagat ttgccaacca gatcctgtct      960

tacggagcag agctggacgc agatcaccct ggcttcaagg acccagtgta tcgggcccgg     1020

agaaagcagt ttgccgatat cgcctacaat tataggcacg gacagccaat ccctcgcgtg     1080

gagtatatgg aggaggagaa gaagacctgg ggcacagtgt tcaagaccct gaagagcctg     1140

tacaagacac acgcctgcta cgagtataac cacatcttcc ccctgctgga gaagtattgt     1200

ggctttcacg aggacaatat ccctcagctg gaggacgtga gccagttcct gcagacctgc     1260

acaggcttta ggctgaggcc agtggcagga ctgctgagct cccgggactt cctgggagga     1320

ctggccttca gagtgtttca ctgcacccag tacatcaggc acggctccaa gccaatgtat     1380

acaccagagc ccgacatctg tcacgagctg ctgggccacg tgcccctgtt tagcgataga     1440

tccttcgccc agttttccca ggagatcgga ctggcatctc tgggagcacc tgacgagtac     1500

atcgagaagc tggccaccat ctattggttc acagtggagt ttggcctgtg caagcagggc     1560

gatagcatca aggcctacgg agcaggactg ctgtctagct tcggcgagct gcagtattgt     1620

ctgtccgaga agccaaagct gctgcccctg gagctggaga agaccgccat ccagaactac     1680

accgtgacag agttccagcc cctgtactat gtggccgagt cttttaacga tgccaaggag     1740

aaggtgagaa atttcgccgc cacaatccct aggcccttca gcgtgcggta cgacccttat     1800

acccagagga tcgaggtgct ggataataca cagcagctga agatcctggc tgactcaatc     1860

aatagcgaaa tcggaatcct gtgctccgcc ctgcagaaaa tcaaatgaat gctttatttg     1920

tgaaatttgt gatgctattg ctttatttgt aaccattata agctgcaata aacaagttaa     1980

caacaacaat tgcattcatt ttatgtttca ggttcagggg gaggtgtggg aggtttttta     2040

aa                                                                    2042


<210>  8
<211>  106
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  truncated AAV2 5'ITR

<400>  8
ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtgg                     106


<210>  9
<211>  143
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  modified AAV2 3'ITR

<400>  9
aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg ctcactgagg       60

ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc      120

gagcgcgcag agagggagtg gcc                                              143


<210>  10
<211>  2356
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  pHMI-hPAH-TC-025 transfer genome (from 5' ITR to 3' ITR)

<400>  10
ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt       60

ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggaatt cacgcgtgga      120

tctgaattca attcacgcgt ggtacctccc taaaatgggc aaacattgca agcagcaaac      180

agcaaacaca cagccctccc tgcctgctga ccttggagct ggggcagagg tcagagacct      240

ctctgggccc atgccacctc caacatccac tcgacccctt ggaatttcgg tggagaggag      300

cagaggttgt cctggcgtgg tttaggtagt gtgagagggg aatgactcct ttcggtaagt      360

gcagtggaag ctgtacactg cccaggcaaa gcgtccgggc agcgtaggcg ggcgactcag      420

atcccagcca gtggacttag cccctgtttg ctcctccgat aactggggtg accttggtta      480

atattcacca gcagcctccc ccgttgcccc tctggatcca ctgcttaaat acggacgagg      540

acagggccct gtctcctcag cttcaggcac caccactgac ctgggacagt gaatcctcta      600

aggtaaatat aaaattttta agtgtataat gtgttaaact actgattcta attgtttctc      660

tcttttagat tccaaccttt ggaactgacc gccaccatgt ccaccgctgt gctggagaac      720

cctgggctgg ggaggaaact gtcagacttc gggcaggaga cttcatacat tgaggataac      780

tgtaaccaga atggcgccat ctctctgatc ttcagcctga aggaggaagt gggcgccctg      840

gcaaaggtgc tgcgcctgtt tgaggagaac gacgtgaatc tgacccacat cgagtcccgg      900

ccttctagac tgaagaagga cgagtacgag ttctttaccc acctggataa gcggtccctg      960

ccagccctga caaacatcat caagatcctg aggcacgaca tcggagcaac cgtgcacgag     1020

ctgtctcggg acaagaagaa ggataccgtg ccctggttcc ctcggacaat ccaggagctg     1080

gatagatttg ccaaccagat cctgtcttac ggagcagagc tggacgcaga tcaccctggc     1140

ttcaaggacc cagtgtatcg ggcccggaga aagcagtttg ccgatatcgc ctacaattat     1200

aggcacggac agccaatccc tcgcgtggag tatatggagg aggagaagaa gacctggggc     1260

acagtgttca agaccctgaa gagcctgtac aagacacacg cctgctacga gtataaccac     1320

atcttccccc tgctggagaa gtattgtggc tttcacgagg acaatatccc tcagctggag     1380

gacgtgagcc agttcctgca gacctgcaca ggctttaggc tgaggccagt ggcaggactg     1440

ctgagctccc gggacttcct gggaggactg gccttcagag tgtttcactg cacccagtac     1500

atcaggcacg gctccaagcc aatgtataca ccagagcccg acatctgtca cgagctgctg     1560

ggccacgtgc ccctgtttag cgatagatcc ttcgcccagt tttcccagga gatcggactg     1620

gcatctctgg gagcacctga cgagtacatc gagaagctgg ccaccatcta ttggttcaca     1680

gtggagtttg gcctgtgcaa gcagggcgat agcatcaagg cctacggagc aggactgctg     1740

tctagcttcg gcgagctgca gtattgtctg tccgagaagc caaagctgct gcccctggag     1800

ctggagaaga ccgccatcca gaactacacc gtgacagagt tccagcccct gtactatgtg     1860

gccgagtctt ttaacgatgc caaggagaag gtgagaaatt tcgccgccac aatccctagg     1920

cccttcagcg tgcggtacga cccttatacc cagaggatcg aggtgctgga taatacacag     1980

cagctgaaga tcctggctga ctcaatcaat agcgaaatcg gaatcctgtg ctccgccctg     2040

cagaaaatca aatgaatgct ttatttgtga aatttgtgat gctattgctt tatttgtaac     2100

cattataagc tgcaataaac aagttaacaa caacaattgc attcatttta tgtttcaggt     2160

tcagggggag gtgtgggagg ttttttaaag catgctgggg agagatcgat ctgaggaacc     2220

cctagtgatg gagttggcca ctccctctct gcgcgctcgc tcgctcactg aggccgggcg     2280

accaaaggtc gcccgacgcc cgggctttgc ccgggcggcc tcagtgagcg agcgagcgcg     2340

cagagaggga gtggcc                                                     2356


<210>  11
<211>  736
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  novel AAV isolate

<400>  11

Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 
1               5                   10                  15      


Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Gln Pro 
            20                  25                  30          


Lys Ala Asn Gln Gln His Gln Asp Asn Ala Arg Gly Leu Val Leu Pro 
        35                  40                  45              


Gly Tyr Lys Tyr Leu Gly Pro Gly Asn Gly Leu Asp Lys Gly Glu Pro 
    50                  55                  60                  


Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 
65                  70                  75                  80  


Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 
                85                  90                  95      


Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly 
            100                 105                 110         


Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Leu Leu Glu Pro 
        115                 120                 125             


Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg 
    130                 135                 140                 


Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ala Gly Ile Gly 
145                 150                 155                 160 


Lys Ser Gly Ala Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr 
                165                 170                 175     


Gly Asp Thr Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro Pro 
            180                 185                 190         


Ala Ala Pro Ser Gly Val Gly Ser Leu Thr Met Ala Ser Gly Gly Gly 
        195                 200                 205             


Ala Pro Val Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser Ser 
    210                 215                 220                 


Ser Gly Asn Trp His Cys Asp Ser Gln Trp Leu Gly Asp Arg Val Ile 
225                 230                 235                 240 


Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 
                245                 250                 255     


Tyr Lys Gln Ile Ser Asn Ser Thr Ser Gly Gly Ser Ser Asn Asp Asn 
            260                 265                 270         


Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg 
        275                 280                 285             


Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn 
    290                 295                 300                 


Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile 
305                 310                 315                 320 


Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn 
                325                 330                 335     


Asn Leu Thr Ser Thr Val Gln Val Phe Ala Asp Ser Asp Tyr Gln Leu 
            340                 345                 350         


Pro Tyr Val Leu Gly Ser Ala His Glu Gly Cys Leu Pro Pro Phe Pro 
        355                 360                 365             


Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp 
    370                 375                 380                 


Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe 
385                 390                 395                 400 


Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Glu 
                405                 410                 415     


Phe Glu Asn Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu 
            420                 425                 430         


Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser 
        435                 440                 445             


Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser 
    450                 455                 460                 


Val Ala Gly Pro Ser Asn Met Ala Val Gln Gly Arg Asn Tyr Ile Pro 
465                 470                 475                 480 


Gly Pro Ser Tyr Arg Gln Gln Arg Val Ser Thr Thr Val Thr Gln Asn 
                485                 490                 495     


Asn Asn Ser Glu Phe Ala Trp Pro Arg Ala Ser Ser Trp Ala Leu Asn 
            500                 505                 510         


Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys 
        515                 520                 525             


Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly 
    530                 535                 540                 


Lys Gln Gly Thr Gly Arg Asp Asn Val Asp Ala Asp Lys Val Met Ile 
545                 550                 555                 560 


Thr Asn Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Ser 
                565                 570                 575     


Tyr Gly Gln Val Ala Thr Asn His Gln Ser Ala Gln Ala Gln Ala Gln 
            580                 585                 590         


Thr Gly Trp Val Gln Asn Gln Gly Ile Leu Pro Gly Met Val Trp Gln 
        595                 600                 605             


Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His 
    610                 615                 620                 


Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Met 
625                 630                 635                 640 


Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 
                645                 650                 655     


Asp Pro Pro Thr Ala Phe Asn Lys Asp Lys Leu Asn Ser Phe Ile Thr 
            660                 665                 670         


Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln 
        675                 680                 685             


Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn 
    690                 695                 700                 


Tyr Tyr Lys Ser Asn Asn Val Glu Phe Ala Val Asn Thr Glu Gly Val 
705                 710                 715                 720 


Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 
                725                 730                 735     


<210>  12
<211>  1359
<212>  DNA
<213>  Homo sapiens

<400>  12
atgtccactg cggtcctgga aaacccaggc ttgggcagga aactctctga ctttggacag       60

gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact gatcttctca      120

ctcaaagaag aagttggtgc attggccaaa gtattgcgct tatttgagga gaatgatgta      180

aacctgaccc acattgaatc tagaccttct cgtttaaaga aagatgagta tgaatttttc      240

acccatttgg ataaacgtag cctgcctgct ctgacaaaca tcatcaagat cttgaggcat      300

gacattggtg ccactgtcca tgagctttca cgagataaga agaaagacac agtgccctgg      360

ttcccaagaa ccattcaaga gctggacaga tttgccaatc agattctcag ctatggagcg      420

gaactggatg ctgaccaccc tggttttaaa gatcctgtgt accgtgcaag acggaagcag      480

tttgctgaca ttgcctacaa ctaccgccat gggcagccca tccctcgagt ggaatacatg      540

gaggaagaaa agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc      600

catgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg tggcttccat      660

gaagataaca ttccccagct ggaagacgtt tctcaattcc tgcagacttg cactggtttc      720

cgcctccgac ctgtggctgg cctgctttcc tctcgggatt tcttgggtgg cctggccttc      780

cgagtcttcc actgcacaca gtacatcaga catggatcca agcccatgta tacccccgaa      840

cctgacatct gccatgagct gttgggacat gtgcccttgt tttcagatcg cagctttgcc      900

cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata cattgaaaag      960

ctcgccacaa tttactggtt tactgtggag tttgggctct gcaaacaagg agactccata     1020

aaggcatatg gtgctgggct cctgtcatcc tttggtgaat tacagtactg cttatcagag     1080

aagccaaagc ttctccccct ggagctggag aagacagcca tccaaaatta cactgtcacg     1140

gagttccagc ccctgtatta cgtggcagag agttttaatg atgccaagga gaaagtaagg     1200

aactttgctg ccacaatacc tcggcccttc tcagttcgct acgacccata cacccaaagg     1260

attgaggtct tggacaatac ccagcagctt aagattttgg ctgattccat taacagtgaa     1320

attggaatcc tttgcagtgc cctccagaaa ataaagtaa                            1359


<210>  13
<211>  452
<212>  PRT
<213>  Homo sapiens

<400>  13

Met Ser Thr Ala Val Leu Glu Asn Pro Gly Leu Gly Arg Lys Leu Ser 
1               5                   10                  15      


Asp Phe Gly Gln Glu Thr Ser Tyr Ile Glu Asp Asn Cys Asn Gln Asn 
            20                  25                  30          


Gly Ala Ile Ser Leu Ile Phe Ser Leu Lys Glu Glu Val Gly Ala Leu 
        35                  40                  45              


Ala Lys Val Leu Arg Leu Phe Glu Glu Asn Asp Val Asn Leu Thr His 
    50                  55                  60                  


Ile Glu Ser Arg Pro Ser Arg Leu Lys Lys Asp Glu Tyr Glu Phe Phe 
65                  70                  75                  80  


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


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


Lys Lys Lys Asp Thr Val Pro Trp Phe Pro Arg Thr Ile Gln Glu Leu 
        115                 120                 125             


Asp Arg Phe Ala Asn Gln Ile Leu Ser Tyr Gly Ala Glu Leu Asp Ala 
    130                 135                 140                 


Asp His Pro Gly Phe Lys Asp Pro Val Tyr Arg Ala Arg Arg Lys Gln 
145                 150                 155                 160 


Phe Ala Asp Ile Ala Tyr Asn Tyr Arg His Gly Gln Pro Ile Pro Arg 
                165                 170                 175     


Val Glu Tyr Met Glu Glu Glu Lys Lys Thr Trp Gly Thr Val Phe Lys 
            180                 185                 190         


Thr Leu Lys Ser Leu Tyr Lys Thr His Ala Cys Tyr Glu Tyr Asn His 
        195                 200                 205             


Ile Phe Pro Leu Leu Glu Lys Tyr Cys Gly Phe His Glu Asp Asn Ile 
    210                 215                 220                 


Pro Gln Leu Glu Asp Val Ser Gln Phe Leu Gln Thr Cys Thr Gly Phe 
225                 230                 235                 240 


Arg Leu Arg Pro Val Ala Gly Leu Leu Ser Ser Arg Asp Phe Leu Gly 
                245                 250                 255     


Gly Leu Ala Phe Arg Val Phe His Cys Thr Gln Tyr Ile Arg His Gly 
            260                 265                 270         


Ser Lys Pro Met Tyr Thr Pro Glu Pro Asp Ile Cys His Glu Leu Leu 
        275                 280                 285             


Gly His Val Pro Leu Phe Ser Asp Arg Ser Phe Ala Gln Phe Ser Gln 
    290                 295                 300                 


Glu Ile Gly Leu Ala Ser Leu Gly Ala Pro Asp Glu Tyr Ile Glu Lys 
305                 310                 315                 320 


Leu Ala Thr Ile Tyr Trp Phe Thr Val Glu Phe Gly Leu Cys Lys Gln 
                325                 330                 335     


Gly Asp Ser Ile Lys Ala Tyr Gly Ala Gly Leu Leu Ser Ser Phe Gly 
            340                 345                 350         


Glu Leu Gln Tyr Cys Leu Ser Glu Lys Pro Lys Leu Leu Pro Leu Glu 
        355                 360                 365             


Leu Glu Lys Thr Ala Ile Gln Asn Tyr Thr Val Thr Glu Phe Gln Pro 
    370                 375                 380                 


Leu Tyr Tyr Val Ala Glu Ser Phe Asn Asp Ala Lys Glu Lys Val Arg 
385                 390                 395                 400 


Asn Phe Ala Ala Thr Ile Pro Arg Pro Phe Ser Val Arg Tyr Asp Pro 
                405                 410                 415     


Tyr Thr Gln Arg Ile Glu Val Leu Asp Asn Thr Gln Gln Leu Lys Ile 
            420                 425                 430         


Leu Ala Asp Ser Ile Asn Ser Glu Ile Gly Ile Leu Cys Ser Ala Leu 
        435                 440                 445             


Gln Lys Ile Lys 
    450         


<210>  14
<211>  592
<212>  DNA
<213>  Homo sapiens

<400>  14
gtaaatttta tggaatgtga atcataattc aatttttcaa catgcgttag gagggacatt       60

tcaaactctt ttttacccta gactttccta ccatcaccca gagtatccag ccaggagggg      120

aggggctaga gacaccagaa gtttagcagg gaggagggcg tagggattcg gggaatgaag      180

ggatgggatt cagactaggg ccaggaccca gggatggaga gaaagagatg agagtggttt      240

gggggcttgg tgacttagag aacagagctg caggctcaga ggcacacagg agtttctggg      300

ctcaccctgc ccccttccaa cccctcagtt cccatcctcc agcagctgtt tgtgtgctgc      360

ctctgaagtc cacactgaac aaacttcagc ctactcatgt ccctaaaatg ggcaaacatt      420

gcaagcagca aacagcaaac acacagccct ccctgcctgc tgaccttgga gctggggcag      480

aggtcagaga cctctctggg cccatgccac ctccaacatc cactcgaccc cttggaattt      540

cggtggagag gagcagaggt tgtcctggcg tggtttaggt agtgtgagag gg              592


<210>  15
<211>  423
<212>  DNA
<213>  Homo sapiens

<400>  15
gctctaaccc actctgatct cccagggcgg cagtaagtct tcagcatcag gcattttggg       60

gtgactcagt aaatggtaga tcttgctacc agtggaacag ccactaagga ttctgcagtg      120

agagcagagg gccagctaag tggtactctc ccagagactg tctgactcac gccaccccct      180

ccaccttgga cacaggacgc tgtggtttct gagccaggta caatgactcc tttcggtaag      240

tgcagtggaa gctgtacact gcccaggcaa agcgtccggg cagcgtaggc gggcgactca      300

gatcccagcc agtggactta gcccctgttt gctcctccga taactggggt gaccttggtt      360

aatattcacc agcagcctcc cccgttgccc ctctggatcc actgcttaaa tacggacgag      420

gac                                                                    423


<210>  16
<211>  145
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  AAV2 5' ITR

<400>  16
ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc       60

cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgcag agagggagtg      120

gccaactcca tcactagggg ttcct                                            145


<210>  17
<211>  145
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  AAV2 3' ITR

<400>  17
aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg ctcactgagg       60

ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc      120

gagcgcgcag agagggagtg gccaa                                            145


<210>  18
<211>  167
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  AAV5 5' ITR

<400>  18
ctctcccccc tgtcgcgttc gctcgctcgc tggctcgttt gggggggtgg cagctcaaag       60

agctgccaga cgacggccct ctggccgtcg cccccccaaa cgagccagcg agcgagcgaa      120

cgcgacaggg gggagagtgc cacactctca agcaaggggg ttttgta                    167


<210>  19
<211>  167
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  AAV5 3' ITR

<400>  19
tacaaaacct ccttgcttga gagtgtggca ctctcccccc tgtcgcgttc gctcgctcgc       60

tggctcgttt gggggggtgg cagctcaaag agctgccaga cgacggccct ctggccgtcg      120

cccccccaaa cgagccagcg agcgagcgaa cgcgacaggg gggagag                    167


<210>  20
<211>  37
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  37 bp additional 3' ITR sequence from wtAAV2

<400>  20
gtagataagt agcatggcgg gttaatcatt aactaca                                37


<210>  21
<211>  180
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  3'ITR with additional 37 bp sequence

<400>  21
gtagataagt agcatggcgg gttaatcatt aactacaagg aacccctagt gatggagttg       60

gccactccct ctctgcgcgc tcgctcgctc actgaggccg ggcgaccaaa ggtcgcccga      120

cgcccgggct ttgcccgggc ggcctcagtg agcgagcgag cgcgcagaga gggagtggcc      180


<210>  22
<211>  621
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AAV2 Rep

<400>  22

Met Pro Gly Phe Tyr Glu Ile Val Ile Lys Val Pro Ser Asp Leu Asp 
1               5                   10                  15      


Glu His Leu Pro Gly Ile Ser Asp Ser Phe Val Asn Trp Val Ala Glu 
            20                  25                  30          


Lys Glu Trp Glu Leu Pro Pro Asp Ser Asp Met Asp Leu Asn Leu Ile 
        35                  40                  45              


Glu Gln Ala Pro Leu Thr Val Ala Glu Lys Leu Gln Arg Asp Phe Leu 
    50                  55                  60                  


Thr Glu Trp Arg Arg Val Ser Lys Ala Pro Glu Ala Leu Phe Phe Val 
65                  70                  75                  80  


Gln Phe Glu Lys Gly Glu Ser Tyr Phe His Met His Val Leu Val Glu 
                85                  90                  95      


Thr Thr Gly Val Lys Ser Met Val Leu Gly Arg Phe Leu Ser Gln Ile 
            100                 105                 110         


Arg Glu Lys Leu Ile Gln Arg Ile Tyr Arg Gly Ile Glu Pro Thr Leu 
        115                 120                 125             


Pro Asn Trp Phe Ala Val Thr Lys Thr Arg Asn Gly Ala Gly Gly Gly 
    130                 135                 140                 


Asn Lys Val Val Asp Glu Cys Tyr Ile Pro Asn Tyr Leu Leu Pro Lys 
145                 150                 155                 160 


Thr Gln Pro Glu Leu Gln Trp Ala Trp Thr Asn Met Glu Gln Tyr Leu 
                165                 170                 175     


Ser Ala Cys Leu Asn Leu Thr Glu Arg Lys Arg Leu Val Ala Gln His 
            180                 185                 190         


Leu Thr His Val Ser Gln Thr Gln Glu Gln Asn Lys Glu Asn Gln Asn 
        195                 200                 205             


Pro Asn Ser Asp Ala Pro Val Ile Arg Ser Lys Thr Ser Ala Arg Tyr 
    210                 215                 220                 


Met Glu Leu Val Gly Trp Leu Val Asp Lys Gly Ile Thr Ser Glu Lys 
225                 230                 235                 240 


Gln Trp Ile Gln Glu Asp Gln Ala Ser Tyr Ile Ser Phe Asn Ala Ala 
                245                 250                 255     


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


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


Pro Val Glu Asp Ile Ser Ser Asn Arg Ile Tyr Lys Ile Leu Glu Leu 
    290                 295                 300                 


Asn Gly Tyr Asp Pro Gln Tyr Ala Ala Ser Val Phe Leu Gly Trp Ala 
305                 310                 315                 320 


Thr Lys Lys Phe Gly Lys Arg Asn Thr Ile Trp Leu Phe Gly Pro Ala 
                325                 330                 335     


Thr Thr Gly Lys Thr Asn Ile Ala Glu Ala Ile Ala His Thr Val Pro 
            340                 345                 350         


Phe Tyr Gly Cys Val Asn Trp Thr Asn Glu Asn Phe Pro Phe Asn Asp 
        355                 360                 365             


Cys Val Asp Lys Met Val Ile Trp Trp Glu Glu Gly Lys Met Thr Ala 
    370                 375                 380                 


Lys Val Val Glu Ser Ala Lys Ala Ile Leu Gly Gly Ser Lys Val Arg 
385                 390                 395                 400 


Val Asp Gln Lys Cys Lys Ser Ser Ala Gln Ile Asp Pro Thr Pro Val 
                405                 410                 415     


Ile Val Thr Ser Asn Thr Asn Met Cys Ala Val Ile Asp Gly Asn Ser 
            420                 425                 430         


Thr Thr Phe Glu His Gln Gln Pro Leu Gln Asp Arg Met Phe Lys Phe 
        435                 440                 445             


Glu Leu Thr Arg Arg Leu Asp His Asp Phe Gly Lys Val Thr Lys Gln 
    450                 455                 460                 


Glu Val Lys Asp Phe Phe Arg Trp Ala Lys Asp His Val Val Glu Val 
465                 470                 475                 480 


Glu His Glu Phe Tyr Val Lys Lys Gly Gly Ala Lys Lys Arg Pro Ala 
                485                 490                 495     


Pro Ser Asp Ala Asp Ile Ser Glu Pro Lys Arg Val Arg Glu Ser Val 
            500                 505                 510         


Ala Gln Pro Ser Thr Ser Asp Ala Glu Ala Ser Ile Asn Tyr Ala Asp 
        515                 520                 525             


Arg Tyr Gln Asn Lys Cys Ser Arg His Val Gly Met Asn Leu Met Leu 
    530                 535                 540                 


Phe Pro Cys Arg Gln Cys Glu Arg Met Asn Gln Asn Ser Asn Ile Cys 
545                 550                 555                 560 


Phe Thr His Gly Gln Lys Asp Cys Leu Glu Cys Phe Pro Val Ser Glu 
                565                 570                 575     


Ser Gln Pro Val Ser Val Val Lys Lys Ala Tyr Gln Lys Leu Cys Tyr 
            580                 585                 590         


Ile His His Ile Met Gly Lys Val Pro Asp Ala Cys Thr Ala Cys Asp 
        595                 600                 605             


Leu Val Asn Val Asp Leu Asp Asp Cys Ile Phe Glu Gln 
    610                 615                 620     


<210>  23
<211>  6020
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  pHMI-hPAH-TC-025 full sequence

<400>  23
aacgccagca acgcggcctt tttacggttc ctggcctttt gctggccttt tgctcacatg       60

ttctttcctg cgttatcccc tgattctgtg gataaccgta ttaccgcctt tgagtgagct      120

gataccgctc gccgcagccg aacgaccgag cgcagcgagt cagtgagcga ggaagcggaa      180

gagcgcccaa tacgcaaacc gcctctcccc gcgcgttggc cgattcatta atgcagcagc      240

tggcgtaata gcgaagaggc ccgcaccgat cgcccttccc aacagttgcg cagcctgaat      300

ggcgaatgga attccagacg attgagcgtc aaaatgtagg tatttccatg agcgtttttc      360

ctgttgcaat ggctggcggt aatattgttc tggatattac cagcaaggcc gatagtttga      420

gttcttctac tcaggcaagt gatgttatta ctaatcaaag aagtattgcg acaacggtta      480

atttgcgtga tggacagact cttttactcg gtggcctcac tgattataaa aacacttctc      540

aggattctgg cgtaccgttc ctgtctaaaa tccctttaat cggcctcctg tttagctccc      600

gctctgattc taacgaggaa agcacgttat acgtgctcgt caaagcaacc atagtacgcg      660

ccctgtagcg gcgcattaag cgcggcgggt gtggtggtta cgcgcagcgt gaccgctaca      720

cttgccagcg ccctagcgcc cgctcctttc gctttcttcc cttcctttct cgccacgttc      780

gccggctttc cccgtcaagc tctaaatcgg gggctccctt tagggttccg atttagtgct      840

ttacggcacc tcgaccccaa aaaacttgat tagggtgatg gttcacgtag tgggccatcg      900

ccctgataga cggtttttcg ccctttgacg ttggagtcca cgttctttaa tagtggactc      960

ttgttccaaa ctggaacaac actcaaccct atctcggtct attcttttga tttataaggg     1020

attttgccga tttcggccta ttggttaaaa aatgagctga tttaacaaaa atttaacgcg     1080

aattttaaca aaatattaac gcttacaatt taaatatttg cttatacaat cttcctgttt     1140

ttggggcttt tctgattatc aaccggggta catatgattg acatgctagt tttacgatta     1200

ccgttcatcg ccctgcgcgc tcgctcgctc actgaggccg cccgggcaaa gcccgggcgt     1260

cgggcgacct ttggtcgccc ggcctcagtg agcgagcgag cgcgcagaga gggagtggaa     1320

ttcacgcgtg gatctgaatt caattcacgc gtggtacctc cctaaaatgg gcaaacattg     1380

caagcagcaa acagcaaaca cacagccctc cctgcctgct gaccttggag ctggggcaga     1440

ggtcagagac ctctctgggc ccatgccacc tccaacatcc actcgacccc ttggaatttc     1500

ggtggagagg agcagaggtt gtcctggcgt ggtttaggta gtgtgagagg ggaatgactc     1560

ctttcggtaa gtgcagtgga agctgtacac tgcccaggca aagcgtccgg gcagcgtagg     1620

cgggcgactc agatcccagc cagtggactt agcccctgtt tgctcctccg ataactgggg     1680

tgaccttggt taatattcac cagcagcctc ccccgttgcc cctctggatc cactgcttaa     1740

atacggacga ggacagggcc ctgtctcctc agcttcaggc accaccactg acctgggaca     1800

gtgaatcctc taaggtaaat ataaaatttt taagtgtata atgtgttaaa ctactgattc     1860

taattgtttc tctcttttag attccaacct ttggaactga ccgccaccat gtccaccgct     1920

gtgctggaga accctgggct ggggaggaaa ctgtcagact tcgggcagga gacttcatac     1980

attgaggata actgtaacca gaatggcgcc atctctctga tcttcagcct gaaggaggaa     2040

gtgggcgccc tggcaaaggt gctgcgcctg tttgaggaga acgacgtgaa tctgacccac     2100

atcgagtccc ggccttctag actgaagaag gacgagtacg agttctttac ccacctggat     2160

aagcggtccc tgccagccct gacaaacatc atcaagatcc tgaggcacga catcggagca     2220

accgtgcacg agctgtctcg ggacaagaag aaggataccg tgccctggtt ccctcggaca     2280

atccaggagc tggatagatt tgccaaccag atcctgtctt acggagcaga gctggacgca     2340

gatcaccctg gcttcaagga cccagtgtat cgggcccgga gaaagcagtt tgccgatatc     2400

gcctacaatt ataggcacgg acagccaatc cctcgcgtgg agtatatgga ggaggagaag     2460

aagacctggg gcacagtgtt caagaccctg aagagcctgt acaagacaca cgcctgctac     2520

gagtataacc acatcttccc cctgctggag aagtattgtg gctttcacga ggacaatatc     2580

cctcagctgg aggacgtgag ccagttcctg cagacctgca caggctttag gctgaggcca     2640

gtggcaggac tgctgagctc ccgggacttc ctgggaggac tggccttcag agtgtttcac     2700

tgcacccagt acatcaggca cggctccaag ccaatgtata caccagagcc cgacatctgt     2760

cacgagctgc tgggccacgt gcccctgttt agcgatagat ccttcgccca gttttcccag     2820

gagatcggac tggcatctct gggagcacct gacgagtaca tcgagaagct ggccaccatc     2880

tattggttca cagtggagtt tggcctgtgc aagcagggcg atagcatcaa ggcctacgga     2940

gcaggactgc tgtctagctt cggcgagctg cagtattgtc tgtccgagaa gccaaagctg     3000

ctgcccctgg agctggagaa gaccgccatc cagaactaca ccgtgacaga gttccagccc     3060

ctgtactatg tggccgagtc ttttaacgat gccaaggaga aggtgagaaa tttcgccgcc     3120

acaatcccta ggcccttcag cgtgcggtac gacccttata cccagaggat cgaggtgctg     3180

gataatacac agcagctgaa gatcctggct gactcaatca atagcgaaat cggaatcctg     3240

tgctccgccc tgcagaaaat caaatgaatg ctttatttgt gaaatttgtg atgctattgc     3300

tttatttgta accattataa gctgcaataa acaagttaac aacaacaatt gcattcattt     3360

tatgtttcag gttcaggggg aggtgtggga ggttttttaa agcatgctgg ggagagatcg     3420

atctgaggaa cccctagtga tggagttggc cactccctct ctgcgcgctc gctcgctcac     3480

tgaggccggg cgaccaaagg tcgcccgacg cccgggcttt gcccgggcgg cctcagtgag     3540

cgagcgagcg cgcagagagg gagtggcccc cccccccccc ccccccggcg attctcttgt     3600

ttgctccaga ctctcaggca atgacctgat agcctttgta gagacctctc aaaaatagct     3660

accctctccg gcatgaattt atcagctaga acggttgaat atcatattga tggtgatttg     3720

actgtctccg gcctttctca cccgtttgaa tctttaccta cacattactc aggcattgca     3780

tttaaaatat atgagggttc taaaaatttt tatccttgcg ttgaaataaa ggcttctccc     3840

gcaaaagtat tacagggtca taatgttttt ggtacaaccg atttagcttt atgctctgag     3900

gctttattgc ttaattttgc taattctttg ccttgcctgt atgatttatt ggatgttgga     3960

atcgcctgat gcggtatttt ctccttacgc atctgtgcgg tatttcacac cgcatatggt     4020

gcactctcag tacaatctgc tctgatgccg catagttaag ccagccccga cacccgccaa     4080

cacccgctga cgcgccctga cgggcttgtc tgctcccggc atccgcttac agacaagctg     4140

tgaccgtctc cgggagctgc atgtgtcaga ggttttcacc gtcatcaccg aaacgcgcga     4200

gacgaaaggg cctcgtgata cgcctatttt tataggttaa tgtcatgata ataatggttt     4260

cttagacgtc aggtggcact tttcggggaa atgtgcgcgg aacccctatt tgtttatttt     4320

tctaaataca ttcaaatatg tatccgctca tgagacaata accctgataa atgcttcaat     4380

aatattgaaa aaggaagagt atgagtattc aacatttccg tgtcgccctt attccctttt     4440

ttgcggcatt ttgccttcct gtttttgctc acccagaaac gctggtgaaa gtaaaagatg     4500

ctgaagatca gttgggtgca cgagtgggtt acatcgaact ggatctcaac agcggtaaga     4560

tccttgagag ttttcgcccc gaagaacgtt ttccaatgat gagcactttt aaagttctgc     4620

tatgtggcgc ggtattatcc cgtattgacg ccgggcaaga gcaactcggt cgccgcatac     4680

actattctca gaatgacttg gttgagtact caccagtcac agaaaagcat cttacggatg     4740

gcatgacagt aagagaatta tgcagtgctg ccataaccat gagtgataac actgcggcca     4800

acttacttct gacaacgatc ggaggaccga aggagctaac cgcttttttg cacaacatgg     4860

gggatcatgt aactcgcctt gatcgttggg aaccggagct gaatgaagcc ataccaaacg     4920

acgagcgtga caccacgatg cctgtagcaa tggcaacaac gttgcgcaaa ctattaactg     4980

gcgaactact tactctagct tcccggcaac aattaataga ctggatggag gcggataaag     5040

ttgcaggacc acttctgcgc tcggcccttc cggctggctg gtttattgct gataaatctg     5100

gagccggtga gcgtgggtct cgcggtatca ttgcagcact ggggccagat ggtaagccct     5160

cccgtatcgt agttatctac acgacgggga gtcaggcaac tatggatgaa cgaaatagac     5220

agatcgctga gataggtgcc tcactgatta agcattggta actgtcagac caagtttact     5280

catatatact ttagattgat ttaaaacttc atttttaatt taaaaggatc taggtgaaga     5340

tcctttttga taatctcatg accaaaatcc cttaacgtga gttttcgttc cactgagcgt     5400

cagaccccgt agaaaagatc aaaggatctt cttgagatcc tttttttctg cgcgtaatct     5460

gctgcttgca aacaaaaaaa ccaccgctac cagcggtggt ttgtttgccg gatcaagagc     5520

taccaactct ttttccgaag gtaactggct tcagcagagc gcagatacca aatactgtcc     5580

ttctagtgta gccgtagtta ggccaccact tcaagaactc tgtagcaccg cctacatacc     5640

tcgctctgct aatcctgtta ccagtggctg ctgccagtgg cgataagtcg tgtcttaccg     5700

ggttggactc aagacgatag ttaccggata aggcgcagcg gtcgggctga acggggggtt     5760

cgtgcacaca gcccagcttg gagcgaacga cctacaccga actgagatac ctacagcgtg     5820

agctatgaga aagcgccacg cttcccgaag ggagaaaggc ggacaggtat ccggtaagcg     5880

gcagggtcgg aacaggagag cgcacgaggg agcttccagg gggaaacgcc tggtatcttt     5940

atagtcctgt cgggtttcgc cacctctgac ttgagcgtcg atttttgtga tgctcgtcag     6000

gggggcggag cctatggaaa                                                 6020


