                         SEQUENCE LISTING

<110>  BioMarin Pharmaceutical Inc.
 
<120>  METHODS OF TREATING PHENYLKETONURIA

<130>  11808-407-228

<140>  PCT/US2019/031252 
<141>  2019-05-08

<150>  62/819,414
<151>  2019-03-15

<150>  62/802,608
<151>  2019-02-07

<150>  62/755,207
<151>  2018-11-02

<150>  62/669,292
<151>  2018-05-09

<160>  23    

<170>  PatentIn version 3.5

<210>  1
<211>  1359
<212>  DNA
<213>  Homo sapiens

<220>
<223>  wild-type human PAH

<400>  1
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 tctcagttcc tgcagacttg cactggtttc      720

cgcctccgac ctgtagctgg 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>  2
<211>  452
<212>  PRT
<213>  Homo sapiens

<220>
<223>  wild-type human PAH

<400>  2

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>  3
<211>  405
<212>  DNA
<213>  Homo sapiens

<220>
<223>  hAAT promoter sequence

<400>  3
gatcttgcta ccagtggaac agccactaag gattctgcag tgagagcaga gggccagcta       60

agtggtactc tcccagagac tgtctgactc acgccacccc ctccaccttg gacacaggac      120

gctgtggttt ctgagccagg tacaatgact cctttcggta agtgcagtgg aagctgtaca      180

ctgcccaggc aaagcgtccg ggcagcgtag gcgggcgact cagatcccag ccagtggact      240

tagcccctgt ttgctcctcc gataactggg gtgaccttgg ttaatattca ccagcagcct      300

cccccgttgc ccctctggat ccactgctta aatacggacg aggacagggc cctgtctcct      360

cagcttcagg caccaccact gacctgggac agtgaatcgt aagta                      405


<210>  4
<211>  321
<212>  DNA
<213>  Homo sapiens

<220>
<223>  HCR enhancer or ApoE enhancer sequence

<400>  4
aggctcagag gcacacagga gtttctgggc tcaccctgcc cccttccaac ccctcagttc       60

ccatcctcca gcagctgttt gtgtgctgcc tctgaagtcc acactgaaca aacttcagcc      120

tactcatgtc cctaaaatgg gcaaacattg caagcagcaa acagcaaaca cacagccctc      180

cctgcctgct gaccttggag ctggggcaga ggtcagagac ctctctgggc ccatgccacc      240

tccaacatcc actcgacccc ttggaatttc ggtggagagg agcagaggtt gtcctggcgt      300

ggtttaggta gtgtgagagg g                                                321


<210>  5

<400>  5
000

<210>  6
<211>  2734
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  synthetic promoter sequence (hAAT promoter, HCR enhancer/ApoE 
enhancer)

<400>  6
aggctcagag gcacacagga gtttctgggc tcaccctgcc cccttccaac ccctcagttc       60

ccatcctcca gcagctgttt gtgtgctgcc tctgaagtcc acactgaaca aacttcagcc      120

tactcatgtc cctaaaatgg gcaaacattg caagcagcaa acagcaaaca cacagccctc      180

cctgcctgct gaccttggag ctggggcaga ggtcagagac ctctctgggc ccatgccacc      240

tccaacatcc actcgacccc ttggaatttc ggtggagagg agcagaggtt gtcctggcgt      300

ggtttaggta gtgtgagagg ggtcgacgat cttgctacca gtggaacagc cactaaggat      360

tctgcagtga gagcagaggg ccagctaagt ggtactctcc cagagactgt ctgactcacg      420

ccaccccctc caccttggac acaggacgct gtggtttctg agccaggtac aatgactcct      480

ttcggtaagt gcagtggaag ctgtacactg cccaggcaaa gcgtccgggc agcgtaggcg      540

ggcgactcag atcccagcca gtggacttag cccctgtttg ctcctccgat aactggggtg      600

accttggtta atattcacca gcagcctccc ccgttgcccc tctggatcca ctgcttaaat      660

acggacgagg acagggccct gtctcctcag cttcaggcac caccactgac ctgggacagt      720

gaatcgtaag tatgcctttc actgcgaggg gttctggaga ggcttctgag ctccccatgg      780

cccaggcagg cagcaggtct ggggcaggag gggggttgtg gagtgggtat ccgcctgctg      840

aggtgcaggg cagatggaga ggctgcagct gagctcctat tttcataata acagcagcca      900

tgagggttgt gtcctgtttc ccagtcctgc ccggtccccc ctcggtacct cctggtggat      960

acactggttc ctgtaagcag aagtggatga gggtgtctag gtctgcagtc ctggcacccc     1020

aggatggggg acaccagcca agatacagca acagcaacaa agcgcagcca tttctttctg     1080

tttgcacagc tcctctgtct gtcgggggct cctgtctgtt gtctcctata agcctcacca     1140

cctctcctac tgcttgggca tgcatctttc tccccttcta tagatgagga ggttaaggtc     1200

cagagagggg tggggaggaa cgccggctca cattctccat cccctccaga tatgaccagg     1260

aacagacctg tgccaggcct cagccttaca tcaaaatggg cctccccatg caccgtggac     1320

ctctgggccc tcctgtccca gtggaggaca ggaagctatg aggggcactg tcacccaggg     1380

ctcaagctgg cattcctgaa taatcgctct gcaccaggcc acggctaagc tcagtgcgtg     1440

attaagcctc ataaccctcc aaggcagtta ctagtgtgat tcccatttta cagatgagga     1500

agatggggac agagaggtga ataactggcc ccaaatcaca caccatccat aattcgggct     1560

caggcacctg gctccagtcc ccaaactctt gaacctggcc ctagtgtcac tgtttctctt     1620

gggtctcagg cgctggatgg ggaacaggaa acctgggctg gacttgaggc ctctctgatg     1680

ctcggtgact tcagacagtt gctcaacctc tctgttctct tgggcaaaac atgataacct     1740

ttgacttctg tcccctcccc tcaccccacc cgaccttgat ctctgaagtg ttggaaggat     1800

ttaatttttc ctgcactgag ttttggagac aggtcaaaaa gatgaccaag gccaaggtgg     1860

ccagtttcct atagaacgcc tctaaaagac ctgcagcaat agcagcaaga actggtattc     1920

tcgagaactt gctgcgcagc aggcacttct tggcatttta tgtgtattta atttcacaat     1980

agctctatga caaagtccac ctttctcatc tccaggaaac tgaggttcag agaggttaag     2040

taacttgtcc aaggtcacac agctaatagc aagttgacgt ggagcaatct ggcctcagag     2100

cctttaattt tagccacaga ctgatgctcc cctcttcatt tagccaggct gcctctgaag     2160

ttttctgatt caagacttct ggcttcagct ttgtacacag agatgattca atgtcaggtt     2220

ttggagtgaa atctgtttaa tcccagacaa aacatttagg attacatctc agttttgtaa     2280

gcaagtagct ctgtgatttt tagtgagtta tttaatgctc tttggggctc aatttttcta     2340

tctataaaat agggctaata atttgcacct tatagggtaa gctttgagga cagattagat     2400

gatacggtgc ctgtaaaaca ccaggtgtta gtaagtgtgg caatgatggt gacgctgagg     2460

ctgatgtttg cttagcatag ggttaggcag ctggcaggca gtaaacagtt ggataattta     2520

atggaaaatt tgccaaactc agatgctagc agctacaatc cagctaccat tctgctttta     2580

ttttatggtt gggataaggc tggattattc tgagtccaag ctaggccctt ttgctaatca     2640

tgttcatacc tcttatcttc ctcccacagc tcctgggcaa cgtgctggtc tgtgtgctgg     2700

cccatcactt tggcaaagaa ttgcgatcgc cacc                                 2734


<210>  7
<211>  1359
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  codon optimised human PAH sequence (GENEius 1/Operon1)

<400>  7
atgagcactg ctgtgctgga gaaccctggc ctgggcagaa agctgtctga ctttggccag       60

gagaccagct acattgagga caactgcaac cagaatggag ccatcagcct gatcttcagc      120

ctgaaggagg aggtgggagc cctggccaag gtgctgagac tgtttgagga gaatgatgtg      180

aacctgaccc acattgagag cagacccagc agactgaaga aggatgagta tgagttcttc      240

acccacctgg acaagagaag cctgcctgcc ctgaccaaca tcatcaagat cctgagacac      300

gatattggag ccactgtgca cgagctgagc agagacaaga agaaggacac tgtgccctgg      360

ttccccagaa ctatccagga gctggacaga tttgccaacc agatcctgag ctatggagct      420

gagctggatg ctgaccaccc tggcttcaag gaccctgtgt acagagccag aagaaagcag      480

tttgctgaca ttgcctacaa ctacagacac ggccagccca tccccagagt ggagtacatg      540

gaggaggaga agaagacctg gggcactgtg ttcaagaccc tgaagagcct gtacaagacc      600

cacgcctgct atgagtacaa ccacatcttc cccctgctgg agaagtactg tggcttccac      660

gaggacaaca tcccccagct ggaggatgtg agccagttcc tgcagacctg cactggcttc      720

agactgagac ctgtggctgg cctgctgagc agcagagact tcctgggggg cctggccttc      780

agagtgttcc actgcaccca gtacatcaga cacggcagca agcccatgta cacccctgag      840

cctgatatct gccacgagct gctgggccac gtgcccctgt tctctgacag aagctttgcc      900

cagttcagcc aggagattgg cctggccagc ctgggagccc ctgatgagta tattgagaag      960

ctggccacta tctactggtt cactgtggag tttggcctgt gcaagcaggg ggacagcatc     1020

aaggcctatg gagctggcct gctgagcagc tttggggagc tgcagtactg cctgtctgag     1080

aagcccaagc tgctgcccct ggagctggag aagactgcca tccagaacta cactgtgact     1140

gagttccagc ccctgtacta tgtggctgag agcttcaatg atgccaagga gaaggtgaga     1200

aactttgctg ccaccatccc cagacccttc tctgtgagat atgaccccta cacccagaga     1260

attgaggtgc tggacaacac ccagcagctg aagatcctgg ctgacagcat caactctgag     1320

attggcatcc tgtgctctgc cctgcagaag atcaagtaa                            1359


<210>  8
<211>  1359
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  codon optimised human PAH sequence (GENEius 2/Operon2)

<400>  8
atgagcactg ctgtgctgga gaaccctggc ctgggcagaa agctgtctga ctttggccag       60

gagaccagct acattgagga caactgcaac cagaatgggg ccatcagcct gatcttcagc      120

ctgaaggagg aggtgggggc cctggccaag gtgctgagac tgtttgagga gaatgatgtg      180

aacctgaccc acattgagag cagacccagc agactgaaga aggatgagta tgagttcttc      240

acccacctgg acaagagaag cctgcctgcc ctgaccaaca tcatcaagat cctgagacac      300

gatattgggg ccactgtgca cgagctgagc agagacaaga agaaggacac tgtgccctgg      360

ttccccagaa ctatccagga gctggacaga tttgccaacc agatcctgag ctatggggct      420

gagctggatg ctgaccaccc tggcttcaag gaccctgtgt acagagccag aagaaagcag      480

tttgctgaca ttgcctacaa ctacagacac ggccagccca tccccagagt ggagtacatg      540

gaggaggaga agaagacctg gggcactgtg ttcaagaccc tgaagagcct gtacaagacc      600

cacgcctgct atgagtacaa ccacatcttc cccctgctgg agaagtactg tggcttccac      660

gaggacaaca tcccccagct ggaggatgtg agccagttcc tgcagacctg cactggcttc      720

agactgagac ctgtggctgg cctgctgagc agcagagact tcctgggggg cctggccttc      780

agagtgttcc actgcaccca gtacatcaga cacggcagca agcccatgta cacccctgag      840

cctgatatct gccacgagct gctgggccac gtgcccctgt tctctgacag aagctttgcc      900

cagttcagcc aggagattgg cctggccagc ctgggggccc ctgatgagta tattgagaag      960

ctggccacta tctactggtt cactgtggag tttggcctgt gcaagcaggg ggacagcatc     1020

aaggcctatg gggctggcct gctgagcagc tttggggagc tgcagtactg cctgtctgag     1080

aagcccaagc tgctgcccct ggagctggag aagactgcca tccagaacta cactgtgact     1140

gagttccagc ccctgtacta tgtggctgag agcttcaatg atgccaagga gaaggtgaga     1200

aactttgctg ccaccatccc cagacccttc tctgtgagat acgaccccta cacccagaga     1260

attgaggtgc tggacaacac ccagcagctg aagatcctgg ctgacagcat caactctgag     1320

attggcatcc tgtgctctgc cctgcagaag atcaagtga                            1359


<210>  9
<211>  1359
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  codon optimised human PAH sequence (Nathwani / NW2-Cop)

<400>  9
atgtccactg ctgtcctgga aaacccaggc ttgggcagga aactctctga ctttggacag       60

gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact gatcttctca      120

ctcaaagaag aagttggtgc attggccaaa gtactgaggt tatttgagga gaatgatgta      180

aacctgaccc acattgaatc tagaccttct aggttaaaga aagatgagta tgaatttttc      240

acccatttgg ataaaaggag cctgcctgct ctgacaaaca tcatcaagat cttgaggcac      300

gacattggtg ccactgtcca cgagctttca agggataaga agaaagacac agtgccctgg      360

ttcccaagaa ctattcaaga gctggacaga tttgccaatc agattctcag ctatggagct      420

gaactggatg ctgaccaccc tggttttaaa gatcctgtgt acagggcaag aaggaagcag      480

tttgctgaca ttgcctacaa ctacaggcat gggcagccca tccctagggt ggaatacatg      540

gaggaagaaa agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc      600

cacgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg tggcttccac      660

gaagataaca ttccccagct ggaagatgtt tctcagttcc tgcagacttg cactggtttc      720

aggctcaggc ctgtagctgg cctgctttcc tctagggatt tcttgggtgg cctggccttc      780

agggtcttcc actgcacaca gtacatcaga cacggctcca agcccatgta tacccctgaa      840

cctgacatct gccacgagct gttgggacac gtgcccttgt tttcagatag gagctttgcc      900

cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata tattgaaaag      960

ctggccacaa tctactggtt tactgtggag tttgggctct gcaaacaagg agactccata     1020

aaggcatatg gtgctgggct cctgtcatcc tttggtgaat tacagtactg cttatcagag     1080

aagccaaagc ttctccccct ggagctggag aagacagcca tccaaaatta cactgtcact     1140

gagttccagc ccctgtatta tgtggcagag agttttaatg atgccaagga gaaagtaagg     1200

aactttgctg ccacaatacc taggcccttc tcagttaggt atgacccata cacccaaagg     1260

attgaggtct tggacaatac ccagcagctt aagattttgg ctgattccat taacagtgaa     1320

attggaatcc tttgcagtgc cctccagaaa atcaagtaa                            1359


<210>  10
<211>  1359
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  codon optimised human PAH sequence (Nathwani-RCG / NW-RCG)

<400>  10
atgtccactg ctgtcctgga aaacccaggc ttgggcagga aactctctga ctttggacag       60

gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact gatcttctca      120

ctcaaagaag aagttggtgc attggccaaa gtactgaggt tatttgagga gaatgatgta      180

aacctgaccc acattgaatc tagaccttct aggttaaaga aagatgagta tgaatttttc      240

acccatttgg ataaaaggag cctgcctgct ctgacaaaca tcatcaagat cttgaggcac      300

gacattggtg ccactgtcca cgagctttca agggataaga agaaagacac agtgccctgg      360

ttcccaagaa ctattcaaga gctggacaga tttgccaatc agattctcag ctatggagct      420

gaactggatg ctgaccaccc tggttttaaa gatcctgtgt acagggcaag aaggaagcag      480

tttgctgaca ttgcctacaa ctacaggcat gggcagccca tccctagggt ggaatacatg      540

gaggaagaaa agaaaacatg gggcacagtg ttcaagactc tgaagtcctt gtataaaacc      600

cacgcttgct atgagtacaa tcacattttt ccacttcttg aaaagtactg tggcttccac      660

gaagataaca ttccccagct ggaagatgtt tctcagttcc tgcagacttg cactggtttc      720

aggctcaggc ctgtagctgg cctgctttcc tctagggatt tcttgggtgg cctggccttc      780

agggtcttcc actgcacaca gtacatcaga cacggctcca agcccatgta tacccctgaa      840

cctgacatct gccacgagct gttgggacac gtgcccttgt tttcagatag gagctttgcc      900

cagttttccc aggaaattgg ccttgcctct ctgggtgcac ctgatgaata tattgaaaag      960

ctggccacaa tttactggtt tactgtggag tttgggctct gcaaacaagg agactccata     1020

aaggcatatg gtgctgggct cctgtcatcc tttggtgaat tacagtactg cttatcagag     1080

aagccaaagc ttctccccct ggagctggag aagacagcca tccaaaatta cactgtcact     1140

gagttccagc ccctgtatta tgtggcagag agttttaatg atgccaagga gaaagtaagg     1200

aactttgctg ccacaatacc taggcccttc tcagttaggt atgacccata cacccaaagg     1260

attgaggtct tggacaatac ccagcagctt aagattttgg ctgattccat taacagtgaa     1320

attggaatcc tttgcagtgc cctccagaaa ataaagtaa                            1359


<210>  11
<211>  1359
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  codon optimised human PAH sequence (ATUM (DNA2.0-op/D20-P))

<400>  11
atgtccactg cggtgttgga aaaccccgga ctgggcagaa agttgtccga cttcggccag       60

gaaacctctt acattgagga caactgcaac cagaacgggg ccatctcact gatcttttcg      120

ctgaaagaag aagtcggagc tctggccaaa gtgctgcgcc tgttcgagga aaacgacgtc      180

aacctgaccc acatcgagtc aagaccgagc aggctgaaga aggatgagta cgagtttttc      240

acccatctcg acaagagatc cctgcctgcc ctgaccaata ttatcaagat tttgcggcac      300

gacattggcg caaccgtgca tgaactctcc cgggacaaga agaaggacac cgtgccgtgg      360

ttcccccgaa ccatccagga actcgaccgc ttcgctaacc agatcctgtc ctacggcgcc      420

gaactggatg ccgatcaccc tggattcaag gacccagtgt acagagcccg gcgcaagcag      480

ttcgccgata tcgcctacaa ttatcggcac ggacagccaa tcccgagggt ggagtacatg      540

gaggaggaaa agaaaacctg gggaactgtg ttcaagacct tgaagtccct gtacaagact      600

cacgcctgct acgagtacaa ccacatcttc cccctgctcg aaaagtactg cgggttccat      660

gaggacaaca tcccccaact ggaagatgtg tcgcagttcc tgcaaacctg taccggattc      720

cggctgaggc ctgtcgcggg acttctgtcc tcccgggatt ttcttggcgg tctggccttc      780

cgggtgttcc actgtactca gtacattaga cacgggagca agcctatgta cactcctgaa      840

cccgacattt gccacgaact cctgggtcat gtgcccctct tctcggatcg gagcttcgcc      900

cagttcagcc aagagatcgg tctggctagc ttgggagcac ccgacgagta catcgagaag      960

ctggccacta tctactggtt taccgtggaa ttcggactgt gcaagcaggg ggactcaatc     1020

aaggcctatg gcgcgggact cctgagctcc ttcggggagc tgcagtactg cctgtccgaa     1080

aagccaaagc tgctccctct tgaactggag aaaacggcca tccagaacta caccgtgacc     1140

gaattccagc cgctctacta cgtcgcggag tccttcaacg atgccaagga gaaggtccgc     1200

aacttcgccg caactatccc gcggccgttt tccgtgcgct atgacccgta cacacaacgc     1260

atcgaagtgc tggacaacac ccagcaactt aagattctgg ccgactcgat caactccgag     1320

attggcattc tgtgctcggc gctgcagaag atcaagtaa                            1359


<210>  12
<211>  1359
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  codon optimised human PAH sequence (ATUM-RCG (DNA2.0-Cop1))

<400>  12
atgtccactg cggtcctgga aaaccctggt ctgggccgca agctttctga ctttggacag       60

gaaacctcat acattgagga caactgtaac caaaatggtg caatcagcct gatcttcagc      120

ctcaaggaag aagtgggagc cctggccaag gtcctgagac tgtttgagga gaatgatgtg      180

aacctgaccc acattgagtc caggccctcc agactgaaga aggatgaata cgaattcttc      240

acccacctgg acaagcgctc cctccctgcc ctcaccaaca tcattaagat cctgcggcac      300

gacattggag ccactgtgca tgagttgagc cgggacaaga agaaggatac tgtgccctgg      360

ttcccgagga ccatccagga actggaccgg tttgccaacc aaattctgtc ctatggagct      420

gaattggatg cagaccaccc tggcttcaag gacccagtgt acagagcaag gagaaagcag      480

tttgcagaca tagcctacaa ctacagacat ggacagccca tcccgagggt ggagtacatg      540

gaagaggaga agaaaacctg gggcactgtg tttaagaccc tcaagagcct gtacaagacc      600

cacgcctgct atgagtacaa ccacatcttc ccactcctgg agaaatactg tggcttccat      660

gaggacaaca tcccacagct ggaggatgtg tcccagttcc tgcagacttg cactggcttc      720

cggttgaggc ctgtggctgg cctgctctcc tcaagggact tcttgggggg actggcattc      780

agggtgttcc actgcaccca atacatcaga cacggcagca agccaatgta cacccctgaa      840

ccggacatct gccacgaact cctgggccac gtccctctgt tctcggacag aagctttgcc      900

cagttctccc aagagattgg ccttgcctcc ctgggggccc ctgatgaata cattgaaaag      960

ctggccacaa tctactggtt cactgtggaa tttggacttt gcaagcaggg agatagcatc     1020

aaggcctacg gggctggact tctgtcctcc ttcggtgaac tgcagtactg tctgtcagag     1080

aagcccaagc tgctgcccct ggaactggag aaaactgcca tccaaaacta cactgtgact     1140

gagttccagc ccctctacta tgtggctgag tccttcaatg atgccaaaga aaaggtcaga     1200

aattttgcgg ccaccattcc taggcctttc tcagtccgct atgaccctta cacccagaga     1260

attgaggtgc tggacaacac ccagcagctc aagatcctgg cagactccat caactcagaa     1320

attgggatct tgtgctcggc cctccaaaag atcaagtaa                            1359


<210>  13
<211>  1359
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  codon optimised human PAH sequence (JCAT (JCAT))

<400>  13
atgagcactg ctgtgctgga gaaccctggc ctgggcagaa agctgtctga ctttggccag       60

gagaccagct acattgagga caactgcaac cagaatgggg ccatcagcct gatcttcagc      120

ctgaaggagg aggtgggggc cctggccaag gtgctgagac tgtttgagga gaatgatgtg      180

aacctgaccc acattgagag cagacccagc agactgaaga aggatgagta tgagttcttc      240

acccacctgg acaagagaag cctgccagcc ctgaccaata ttatcaagat cctgaggcac      300

gatattgggg ccacagtgca cgagctgagc agagacaaga agaaggacac agtgccctgg      360

ttccccagga ctatccagga gctggacagg tttgccaacc agatcctgag ctacggagct      420

gagctggatg cagaccaccc tggcttcaag gaccctgtgt acagagccag gagaaagcag      480

tttgcagata tagcctacaa ctacaggcac ggccagccaa tccctagagt ggagtacatg      540

gaggaggaga agaagacctg gggcactgtg ttcaagaccc tgaagagcct gtacaagacc      600

cacgcctgct acgagtacaa ccacatcttc cccctgctgg agaagtactg tggcttccac      660

gaggacaaca tcccccagct ggaggatgtg agccagttcc tgcagacctg cacaggcttc      720

aggctgagac cagtggcagg cctgctgagc agcagggact tcctgggggg cctggccttc      780

agagtgttcc actgcaccca gtatatcagg cacggcagca agccaatgta cacccctgag      840

ccagatatct gccacgagct gctgggccac gttcccctgt tctcagacag aagctttgcc      900

cagttcagcc aggagattgg cctggccagc ctgggggccc ctgacgagta tattgagaag      960

ctggccacta tctactggtt cacagtggag tttggcctgt gcaagcaggg ggacagcatc     1020

aaggcctatg gggctggcct gctgagcagc tttggggagc tgcagtactg cctgtcagag     1080

aagccaaagc tgctgcccct ggagctggag aagacagcta tccagaacta cactgtgact     1140

gagttccagc ccctgtacta tgtggcagag agcttcaatg atgccaagga gaaggtgaga     1200

aactttgctg ccaccatccc caggcccttc tctgtgagat atgaccccta cacccagagg     1260

attgaggtgc tggacaacac ccagcagctg aagatcctgg cagacagcat caacagtgag     1320

attggtatcc tgtgctctgc cctgcagaag atcaagtaa                            1359


<210>  14
<211>  2002
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  composite globin/AIAT intron nucleic acid sequence

<400>  14
tgcctttcac tgcgaggggt tctggagagg cttctgagct ccccatggcc caggcaggca       60

gcaggtctgg ggcaggaggg gggttgtgga gtgggtatcc gcctgctgag gtgcagggca      120

gatggagagg ctgcagctga gctcctattt tcataataac agcagccatg agggttgtgt      180

cctgtttccc agtcctgccc ggtcccccct cggtacctcc tggtggatac actggttcct      240

gtaagcagaa gtggatgagg gtgtctaggt ctgcagtcct ggcaccccag gatgggggac      300

accagccaag atacagcaac agcaacaaag cgcagccatt tctttctgtt tgcacagctc      360

ctctgtctgt cgggggctcc tgtctgttgt ctcctataag cctcaccacc tctcctactg      420

cttgggcatg catctttctc cccttctata gatgaggagg ttaaggtcca gagaggggtg      480

gggaggaacg ccggctcaca ttctccatcc cctccagata tgaccaggaa cagacctgtg      540

ccaggcctca gccttacatc aaaatgggcc tccccatgca ccgtggacct ctgggccctc      600

ctgtcccagt ggaggacagg aagctatgag gggcactgtc acccagggct caagctggca      660

ttcctgaata atcgctctgc accaggccac ggctaagctc agtgcgtgat taagcctcat      720

aaccctccaa ggcagttact agtgtgattc ccattttaca gatgaggaag atggggacag      780

agaggtgaat aactggcccc aaatcacaca ccatccataa ttcgggctca ggcacctggc      840

tccagtcccc aaactcttga acctggccct agtgtcactg tttctcttgg gtctcaggcg      900

ctggatgggg aacaggaaac ctgggctgga cttgaggcct ctctgatgct cggtgacttc      960

agacagttgc tcaacctctc tgttctcttg ggcaaaacat gataaccttt gacttctgtc     1020

ccctcccctc accccacccg accttgatct ctgaagtgtt ggaaggattt aatttttcct     1080

gcactgagtt ttggagacag gtcaaaaaga tgaccaaggc caaggtggcc agtttcctat     1140

agaacgcctc taaaagacct gcagcaatag cagcaagaac tggtattctc gagaacttgc     1200

tgcgcagcag gcacttcttg gcattttatg tgtatttaat ttcacaatag ctctatgaca     1260

aagtccacct ttctcatctc caggaaactg aggttcagag aggttaagta acttgtccaa     1320

ggtcacacag ctaatagcaa gttgacgtgg agcaatctgg cctcagagcc tttaatttta     1380

gccacagact gatgctcccc tcttcattta gccaggctgc ctctgaagtt ttctgattca     1440

agacttctgg cttcagcttt gtacacagag atgattcaat gtcaggtttt ggagtgaaat     1500

ctgtttaatc ccagacaaaa catttaggat tacatctcag ttttgtaagc aagtagctct     1560

gtgattttta gtgagttatt taatgctctt tggggctcaa tttttctatc tataaaatag     1620

ggctaataat ttgcacctta tagggtaagc tttgaggaca gattagatga tacggtgcct     1680

gtaaaacacc aggtgttagt aagtgtggca atgatggtga cgctgaggct gatgtttgct     1740

tagcataggg ttaggcagct ggcaggcagt aaacagttgg ataatttaat ggaaaatttg     1800

ccaaactcag atgctagcag ctacaatcca gctaccattc tgcttttatt ttatggttgg     1860

gataaggctg gattattctg agtccaagct aggccctttt gctaatcatg ttcatacctc     1920

ttatcttcct cccacagctc ctgggcaacg tgctggtctg tgtgctggcc catcactttg     1980

gcaaagaatt gcgatcgcca cc                                              2002


<210>  15
<211>  2822
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Vector 1 (ApoE-HCR-hAAT.GI.hPAH.bGH) nucleic acid sequence

<400>  15
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc       60

gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc tgcggccgca cgcgtaggct cagaggcaca caggagtttc      180

tgggctcacc ctgccccctt ccaacccctc agttcccatc ctccagcagc tgtttgtgtg      240

ctgcctctga agtccacact gaacaaactt cagcctactc atgtccctaa aatgggcaaa      300

cattgcaagc agcaaacagc aaacacacag ccctccctgc ctgctgacct tggagctggg      360

gcagaggtca gagacctctc tgggcccatg ccacctccaa catccactcg accccttgga      420

atttcggtgg agaggagcag aggttgtcct ggcgtggttt aggtagtgtg agaggggtcg      480

acgatcttgc taccagtgga acagccacta aggattctgc agtgagagca gagggccagc      540

taagtggtac tctcccagag actgtctgac tcacgccacc ccctccacct tggacacagg      600

acgctgtggt ttctgagcca ggtacaatga ctcctttcgg taagtgcagt ggaagctgta      660

cactgcccag gcaaagcgtc cgggcagcgt aggcgggcga ctcagatccc agccagtgga      720

cttagcccct gtttgctcct ccgataactg gggtgacctt ggttaatatt caccagcagc      780

ctcccccgtt gcccctctgg atccactgct taaatacgga cgaggacagg gccctgtctc      840

ctcagcttca ggcaccacca ctgacctggg acagtgaatc gtaagtacta gcagctacaa      900

tccagctacc attctgcttt tattttatgg ttgggataag gctggattat tctgagtcca      960

agctaggccc ttttgctaat catgttcata cctcttatct tcctcccaca gctcctgggc     1020

aacgtgctgg tctgtgtgct ggcccatcac tttggcaaag aattgcgatc gccaccatgt     1080

ccactgcggt cctggaaaac ccaggcttgg gcaggaaact ctctgacttt ggacaggaaa     1140

caagctatat tgaagacaac tgcaatcaaa atggtgccat atcactgatc ttctcactca     1200

aagaagaagt tggtgcattg gccaaagtat tgcgcttatt tgaggagaat gatgtaaacc     1260

tgacccacat tgaatctaga ccttctcgtt taaagaaaga tgagtatgaa tttttcaccc     1320

atttggataa acgtagcctg cctgctctga caaacatcat caagatcttg aggcatgaca     1380

ttggtgccac tgtccatgag ctttcacgag ataagaagaa agacacagtg ccctggttcc     1440

caagaaccat tcaagagctg gacagatttg ccaatcagat tctcagctat ggagcggaac     1500

tggatgctga ccaccctggt tttaaagatc ctgtgtaccg tgcaagacgg aagcagtttg     1560

ctgacattgc ctacaactac cgccatgggc agcccatccc tcgagtggaa tacatggagg     1620

aagaaaagaa aacatggggc acagtgttca agactctgaa gtccttgtat aaaacccatg     1680

cttgctatga gtacaatcac atttttccac ttcttgaaaa gtactgtggc ttccatgaag     1740

ataacattcc ccagctggaa gacgtttctc agttcctgca gacttgcact ggtttccgcc     1800

tccgacctgt agctggcctg ctttcctctc gggatttctt gggtggcctg gccttccgag     1860

tcttccactg cacacagtac atcagacatg gatccaagcc catgtatacc cccgaacctg     1920

acatctgcca tgagctgttg ggacatgtgc ccttgttttc agatcgcagc tttgcccagt     1980

tttcccagga aattggcctt gcctctctgg gtgcacctga tgaatacatt gaaaagctcg     2040

ccacaattta ctggtttact gtggagtttg ggctctgcaa acaaggagac tccataaagg     2100

catatggtgc tgggctcctg tcatcctttg gtgaattaca gtactgctta tcagagaagc     2160

caaagcttct ccccctggag ctggagaaga cagccatcca aaattacact gtcacggagt     2220

tccagcccct gtattacgtg gcagagagtt ttaatgatgc caaggagaaa gtaaggaact     2280

ttgctgccac aatacctcgg cccttctcag ttcgctacga cccatacacc caaaggattg     2340

aggtcttgga caatacccag cagcttaaga ttttggctga ttccattaac agtgaaattg     2400

gaatcctttg cagtgccctc cagaaaataa agtaacctcg agctgtgcct tctagttgcc     2460

agccatctgt tgtttgcccc tcccccgtgc cttccttgac cctggaaggt gccactccca     2520

ctgtcctttc ctaataaaat gaggaaattg catcgcattg tctgagtagg tgtcattcta     2580

ttctgggggg tggggtgggg caggacagca agggggagga ttgggaagac aatagcaggc     2640

atgctgggga tgcggtgggc tctatggacc ggtgcggccg caggaacccc tagtgatgga     2700

gttggccact ccctctctgc gcgctcgctc gctcactgag gccgggcgac caaaggtcgc     2760

ccgacgcccg ggctttgccc gggcggcctc agtgagcgag cgagcgcgca gctgcctgca     2820

gg                                                                    2822


<210>  16
<211>  2822
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  GENEius1 (ApoE-HCR-hAAT.GI.hPAHco1.bGH) nucleic acid sequence

<400>  16
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc       60

gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc tgcggccgca cgcgtaggct cagaggcaca caggagtttc      180

tgggctcacc ctgccccctt ccaacccctc agttcccatc ctccagcagc tgtttgtgtg      240

ctgcctctga agtccacact gaacaaactt cagcctactc atgtccctaa aatgggcaaa      300

cattgcaagc agcaaacagc aaacacacag ccctccctgc ctgctgacct tggagctggg      360

gcagaggtca gagacctctc tgggcccatg ccacctccaa catccactcg accccttgga      420

atttcggtgg agaggagcag aggttgtcct ggcgtggttt aggtagtgtg agaggggtcg      480

acgatcttgc taccagtgga acagccacta aggattctgc agtgagagca gagggccagc      540

taagtggtac tctcccagag actgtctgac tcacgccacc ccctccacct tggacacagg      600

acgctgtggt ttctgagcca ggtacaatga ctcctttcgg taagtgcagt ggaagctgta      660

cactgcccag gcaaagcgtc cgggcagcgt aggcgggcga ctcagatccc agccagtgga      720

cttagcccct gtttgctcct ccgataactg gggtgacctt ggttaatatt caccagcagc      780

ctcccccgtt gcccctctgg atccactgct taaatacgga cgaggacagg gccctgtctc      840

ctcagcttca ggcaccacca ctgacctggg acagtgaatc gtaagtacta gcagctacaa      900

tccagctacc attctgcttt tattttatgg ttgggataag gctggattat tctgagtcca      960

agctaggccc ttttgctaat catgttcata cctcttatct tcctcccaca gctcctgggc     1020

aacgtgctgg tctgtgtgct ggcccatcac tttggcaaag aattgcgatc gccaccatga     1080

gcactgctgt gctggagaac cctggcctgg gcagaaagct gtctgacttt ggccaggaga     1140

ccagctacat tgaggacaac tgcaaccaga atggagccat cagcctgatc ttcagcctga     1200

aggaggaggt gggagccctg gccaaggtgc tgagactgtt tgaggagaat gatgtgaacc     1260

tgacccacat tgagagcaga cccagcagac tgaagaagga tgagtatgag ttcttcaccc     1320

acctggacaa gagaagcctg cctgccctga ccaacatcat caagatcctg agacacgata     1380

ttggagccac tgtgcacgag ctgagcagag acaagaagaa ggacactgtg ccctggttcc     1440

ccagaactat ccaggagctg gacagatttg ccaaccagat cctgagctat ggagctgagc     1500

tggatgctga ccaccctggc ttcaaggacc ctgtgtacag agccagaaga aagcagtttg     1560

ctgacattgc ctacaactac agacacggcc agcccatccc cagagtggag tacatggagg     1620

aggagaagaa gacctggggc actgtgttca agaccctgaa gagcctgtac aagacccacg     1680

cctgctatga gtacaaccac atcttccccc tgctggagaa gtactgtggc ttccacgagg     1740

acaacatccc ccagctggag gatgtgagcc agttcctgca gacctgcact ggcttcagac     1800

tgagacctgt ggctggcctg ctgagcagca gagacttcct ggggggcctg gccttcagag     1860

tgttccactg cacccagtac atcagacacg gcagcaagcc catgtacacc cctgagcctg     1920

atatctgcca cgagctgctg ggccacgtgc ccctgttctc tgacagaagc tttgcccagt     1980

tcagccagga gattggcctg gccagcctgg gagcccctga tgagtatatt gagaagctgg     2040

ccactatcta ctggttcact gtggagtttg gcctgtgcaa gcagggggac agcatcaagg     2100

cctatggagc tggcctgctg agcagctttg gggagctgca gtactgcctg tctgagaagc     2160

ccaagctgct gcccctggag ctggagaaga ctgccatcca gaactacact gtgactgagt     2220

tccagcccct gtactatgtg gctgagagct tcaatgatgc caaggagaag gtgagaaact     2280

ttgctgccac catccccaga cccttctctg tgagatatga cccctacacc cagagaattg     2340

aggtgctgga caacacccag cagctgaaga tcctggctga cagcatcaac tctgagattg     2400

gcatcctgtg ctctgccctg cagaagatca agtaacctcg agctgtgcct tctagttgcc     2460

agccatctgt tgtttgcccc tcccccgtgc cttccttgac cctggaaggt gccactccca     2520

ctgtcctttc ctaataaaat gaggaaattg catcgcattg tctgagtagg tgtcattcta     2580

ttctgggggg tggggtgggg caggacagca agggggagga ttgggaagac aatagcaggc     2640

atgctgggga tgcggtgggc tctatggacc ggtgcggccg caggaacccc tagtgatgga     2700

gttggccact ccctctctgc gcgctcgctc gctcactgag gccgggcgac caaaggtcgc     2760

ccgacgcccg ggctttgccc gggcggcctc agtgagcgag cgagcgcgca gctgcctgca     2820

gg                                                                    2822


<210>  17
<211>  4635
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Large Intron-Vector 1 (ApoE-HCR-hAAT.cG-AIATI.hPAH.bGH) sequence

<400>  17
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc       60

gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc tgcggccgca cgcgtaggct cagaggcaca caggagtttc      180

tgggctcacc ctgccccctt ccaacccctc agttcccatc ctccagcagc tgtttgtgtg      240

ctgcctctga agtccacact gaacaaactt cagcctactc atgtccctaa aatgggcaaa      300

cattgcaagc agcaaacagc aaacacacag ccctccctgc ctgctgacct tggagctggg      360

gcagaggtca gagacctctc tgggcccatg ccacctccaa catccactcg accccttgga      420

atttcggtgg agaggagcag aggttgtcct ggcgtggttt aggtagtgtg agaggggtcg      480

acgatcttgc taccagtgga acagccacta aggattctgc agtgagagca gagggccagc      540

taagtggtac tctcccagag actgtctgac tcacgccacc ccctccacct tggacacagg      600

acgctgtggt ttctgagcca ggtacaatga ctcctttcgg taagtgcagt ggaagctgta      660

cactgcccag gcaaagcgtc cgggcagcgt aggcgggcga ctcagatccc agccagtgga      720

cttagcccct gtttgctcct ccgataactg gggtgacctt ggttaatatt caccagcagc      780

ctcccccgtt gcccctctgg atccactgct taaatacgga cgaggacagg gccctgtctc      840

ctcagcttca ggcaccacca ctgacctggg acagtgaatc gtaagtatgc ctttcactgc      900

gaggggttct ggagaggctt ctgagctccc catggcccag gcaggcagca ggtctggggc      960

aggagggggg ttgtggagtg ggtatccgcc tgctgaggtg cagggcagat ggagaggctg     1020

cagctgagct cctattttca taataacagc agccatgagg gttgtgtcct gtttcccagt     1080

cctgcccggt cccccctcgg tacctcctgg tggatacact ggttcctgta agcagaagtg     1140

gatgagggtg tctaggtctg cagtcctggc accccaggat gggggacacc agccaagata     1200

cagcaacagc aacaaagcgc agccatttct ttctgtttgc acagctcctc tgtctgtcgg     1260

gggctcctgt ctgttgtctc ctataagcct caccacctct cctactgctt gggcatgcat     1320

ctttctcccc ttctatagat gaggaggtta aggtccagag aggggtgggg aggaacgccg     1380

gctcacattc tccatcccct ccagatatga ccaggaacag acctgtgcca ggcctcagcc     1440

ttacatcaaa atgggcctcc ccatgcaccg tggacctctg ggccctcctg tcccagtgga     1500

ggacaggaag ctatgagggg cactgtcacc cagggctcaa gctggcattc ctgaataatc     1560

gctctgcacc aggccacggc taagctcagt gcgtgattaa gcctcataac cctccaaggc     1620

agttactagt gtgattccca ttttacagat gaggaagatg gggacagaga ggtgaataac     1680

tggccccaaa tcacacacca tccataattc gggctcaggc acctggctcc agtccccaaa     1740

ctcttgaacc tggccctagt gtcactgttt ctcttgggtc tcaggcgctg gatggggaac     1800

aggaaacctg ggctggactt gaggcctctc tgatgctcgg tgacttcaga cagttgctca     1860

acctctctgt tctcttgggc aaaacatgat aacctttgac ttctgtcccc tcccctcacc     1920

ccacccgacc ttgatctctg aagtgttgga aggatttaat ttttcctgca ctgagttttg     1980

gagacaggtc aaaaagatga ccaaggccaa ggtggccagt ttcctataga acgcctctaa     2040

aagacctgca gcaatagcag caagaactgg tattctcgag aacttgctgc gcagcaggca     2100

cttcttggca ttttatgtgt atttaatttc acaatagctc tatgacaaag tccacctttc     2160

tcatctccag gaaactgagg ttcagagagg ttaagtaact tgtccaaggt cacacagcta     2220

atagcaagtt gacgtggagc aatctggcct cagagccttt aattttagcc acagactgat     2280

gctcccctct tcatttagcc aggctgcctc tgaagttttc tgattcaaga cttctggctt     2340

cagctttgta cacagagatg attcaatgtc aggttttgga gtgaaatctg tttaatccca     2400

gacaaaacat ttaggattac atctcagttt tgtaagcaag tagctctgtg atttttagtg     2460

agttatttaa tgctctttgg ggctcaattt ttctatctat aaaatagggc taataatttg     2520

caccttatag ggtaagcttt gaggacagat tagatgatac ggtgcctgta aaacaccagg     2580

tgttagtaag tgtggcaatg atggtgacgc tgaggctgat gtttgcttag catagggtta     2640

ggcagctggc aggcagtaaa cagttggata atttaatgga aaatttgcca aactcagatg     2700

ctagcagcta caatccagct accattctgc ttttatttta tggttgggat aaggctggat     2760

tattctgagt ccaagctagg cccttttgct aatcatgttc atacctctta tcttcctccc     2820

acagctcctg ggcaacgtgc tggtctgtgt gctggcccat cactttggca aagaattgcg     2880

atcgccacca tgtccactgc ggtcctggaa aacccaggct tgggcaggaa actctctgac     2940

tttggacagg aaacaagcta tattgaagac aactgcaatc aaaatggtgc catatcactg     3000

atcttctcac tcaaagaaga agttggtgca ttggccaaag tattgcgctt atttgaggag     3060

aatgatgtaa acctgaccca cattgaatct agaccttctc gtttaaagaa agatgagtat     3120

gaatttttca cccatttgga taaacgtagc ctgcctgctc tgacaaacat catcaagatc     3180

ttgaggcatg acattggtgc cactgtccat gagctttcac gagataagaa gaaagacaca     3240

gtgccctggt tcccaagaac cattcaagag ctggacagat ttgccaatca gattctcagc     3300

tatggagcgg aactggatgc tgaccaccct ggttttaaag atcctgtgta ccgtgcaaga     3360

cggaagcagt ttgctgacat tgcctacaac taccgccatg ggcagcccat ccctcgagtg     3420

gaatacatgg aggaagaaaa gaaaacatgg ggcacagtgt tcaagactct gaagtccttg     3480

tataaaaccc atgcttgcta tgagtacaat cacatttttc cacttcttga aaagtactgt     3540

ggcttccatg aagataacat tccccagctg gaagacgttt ctcagttcct gcagacttgc     3600

actggtttcc gcctccgacc tgtagctggc ctgctttcct ctcgggattt cttgggtggc     3660

ctggccttcc gagtcttcca ctgcacacag tacatcagac atggatccaa gcccatgtat     3720

acccccgaac ctgacatctg ccatgagctg ttgggacatg tgcccttgtt ttcagatcgc     3780

agctttgccc agttttccca ggaaattggc cttgcctctc tgggtgcacc tgatgaatac     3840

attgaaaagc tcgccacaat ttactggttt actgtggagt ttgggctctg caaacaagga     3900

gactccataa aggcatatgg tgctgggctc ctgtcatcct ttggtgaatt acagtactgc     3960

ttatcagaga agccaaagct tctccccctg gagctggaga agacagccat ccaaaattac     4020

actgtcacgg agttccagcc cctgtattac gtggcagaga gttttaatga tgccaaggag     4080

aaagtaagga actttgctgc cacaatacct cggcccttct cagttcgcta cgacccatac     4140

acccaaagga ttgaggtctt ggacaatacc cagcagctta agattttggc tgattccatt     4200

aacagtgaaa ttggaatcct ttgcagtgcc ctccagaaaa taaagtaacc tcgagctgtg     4260

ccttctagtt gccagccatc tgttgtttgc ccctcccccg tgccttcctt gaccctggaa     4320

ggtgccactc ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca ttgtctgagt     4380

aggtgtcatt ctattctggg gggtggggtg gggcaggaca gcaaggggga ggattgggaa     4440

gacaatagca ggcatgctgg ggatgcggtg ggctctatgg accggtgcgg ccgcaggaac     4500

ccctagtgat ggagttggcc actccctctc tgcgcgctcg ctcgctcact gaggccgggc     4560

gaccaaaggt cgcccgacgc ccgggctttg cccgggcggc ctcagtgagc gagcgagcgc     4620

gcagctgcct gcagg                                                      4635


<210>  18
<211>  4635
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Large Intron-GENEius 1(ApoE-HCR-hAAT.cG-AIATI.hPAHco1.bGH) sequence

<400>  18
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc       60

gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc tgcggccgca cgcgtaggct cagaggcaca caggagtttc      180

tgggctcacc ctgccccctt ccaacccctc agttcccatc ctccagcagc tgtttgtgtg      240

ctgcctctga agtccacact gaacaaactt cagcctactc atgtccctaa aatgggcaaa      300

cattgcaagc agcaaacagc aaacacacag ccctccctgc ctgctgacct tggagctggg      360

gcagaggtca gagacctctc tgggcccatg ccacctccaa catccactcg accccttgga      420

atttcggtgg agaggagcag aggttgtcct ggcgtggttt aggtagtgtg agaggggtcg      480

acgatcttgc taccagtgga acagccacta aggattctgc agtgagagca gagggccagc      540

taagtggtac tctcccagag actgtctgac tcacgccacc ccctccacct tggacacagg      600

acgctgtggt ttctgagcca ggtacaatga ctcctttcgg taagtgcagt ggaagctgta      660

cactgcccag gcaaagcgtc cgggcagcgt aggcgggcga ctcagatccc agccagtgga      720

cttagcccct gtttgctcct ccgataactg gggtgacctt ggttaatatt caccagcagc      780

ctcccccgtt gcccctctgg atccactgct taaatacgga cgaggacagg gccctgtctc      840

ctcagcttca ggcaccacca ctgacctggg acagtgaatc gtaagtatgc ctttcactgc      900

gaggggttct ggagaggctt ctgagctccc catggcccag gcaggcagca ggtctggggc      960

aggagggggg ttgtggagtg ggtatccgcc tgctgaggtg cagggcagat ggagaggctg     1020

cagctgagct cctattttca taataacagc agccatgagg gttgtgtcct gtttcccagt     1080

cctgcccggt cccccctcgg tacctcctgg tggatacact ggttcctgta agcagaagtg     1140

gatgagggtg tctaggtctg cagtcctggc accccaggat gggggacacc agccaagata     1200

cagcaacagc aacaaagcgc agccatttct ttctgtttgc acagctcctc tgtctgtcgg     1260

gggctcctgt ctgttgtctc ctataagcct caccacctct cctactgctt gggcatgcat     1320

ctttctcccc ttctatagat gaggaggtta aggtccagag aggggtgggg aggaacgccg     1380

gctcacattc tccatcccct ccagatatga ccaggaacag acctgtgcca ggcctcagcc     1440

ttacatcaaa atgggcctcc ccatgcaccg tggacctctg ggccctcctg tcccagtgga     1500

ggacaggaag ctatgagggg cactgtcacc cagggctcaa gctggcattc ctgaataatc     1560

gctctgcacc aggccacggc taagctcagt gcgtgattaa gcctcataac cctccaaggc     1620

agttactagt gtgattccca ttttacagat gaggaagatg gggacagaga ggtgaataac     1680

tggccccaaa tcacacacca tccataattc gggctcaggc acctggctcc agtccccaaa     1740

ctcttgaacc tggccctagt gtcactgttt ctcttgggtc tcaggcgctg gatggggaac     1800

aggaaacctg ggctggactt gaggcctctc tgatgctcgg tgacttcaga cagttgctca     1860

acctctctgt tctcttgggc aaaacatgat aacctttgac ttctgtcccc tcccctcacc     1920

ccacccgacc ttgatctctg aagtgttgga aggatttaat ttttcctgca ctgagttttg     1980

gagacaggtc aaaaagatga ccaaggccaa ggtggccagt ttcctataga acgcctctaa     2040

aagacctgca gcaatagcag caagaactgg tattctcgag aacttgctgc gcagcaggca     2100

cttcttggca ttttatgtgt atttaatttc acaatagctc tatgacaaag tccacctttc     2160

tcatctccag gaaactgagg ttcagagagg ttaagtaact tgtccaaggt cacacagcta     2220

atagcaagtt gacgtggagc aatctggcct cagagccttt aattttagcc acagactgat     2280

gctcccctct tcatttagcc aggctgcctc tgaagttttc tgattcaaga cttctggctt     2340

cagctttgta cacagagatg attcaatgtc aggttttgga gtgaaatctg tttaatccca     2400

gacaaaacat ttaggattac atctcagttt tgtaagcaag tagctctgtg atttttagtg     2460

agttatttaa tgctctttgg ggctcaattt ttctatctat aaaatagggc taataatttg     2520

caccttatag ggtaagcttt gaggacagat tagatgatac ggtgcctgta aaacaccagg     2580

tgttagtaag tgtggcaatg atggtgacgc tgaggctgat gtttgcttag catagggtta     2640

ggcagctggc aggcagtaaa cagttggata atttaatgga aaatttgcca aactcagatg     2700

ctagcagcta caatccagct accattctgc ttttatttta tggttgggat aaggctggat     2760

tattctgagt ccaagctagg cccttttgct aatcatgttc atacctctta tcttcctccc     2820

acagctcctg ggcaacgtgc tggtctgtgt gctggcccat cactttggca aagaattgcg     2880

atcgccacca tgagcactgc tgtgctggag aaccctggcc tgggcagaaa gctgtctgac     2940

tttggccagg agaccagcta cattgaggac aactgcaacc agaatggagc catcagcctg     3000

atcttcagcc tgaaggagga ggtgggagcc ctggccaagg tgctgagact gtttgaggag     3060

aatgatgtga acctgaccca cattgagagc agacccagca gactgaagaa ggatgagtat     3120

gagttcttca cccacctgga caagagaagc ctgcctgccc tgaccaacat catcaagatc     3180

ctgagacacg atattggagc cactgtgcac gagctgagca gagacaagaa gaaggacact     3240

gtgccctggt tccccagaac tatccaggag ctggacagat ttgccaacca gatcctgagc     3300

tatggagctg agctggatgc tgaccaccct ggcttcaagg accctgtgta cagagccaga     3360

agaaagcagt ttgctgacat tgcctacaac tacagacacg gccagcccat ccccagagtg     3420

gagtacatgg aggaggagaa gaagacctgg ggcactgtgt tcaagaccct gaagagcctg     3480

tacaagaccc acgcctgcta tgagtacaac cacatcttcc ccctgctgga gaagtactgt     3540

ggcttccacg aggacaacat cccccagctg gaggatgtga gccagttcct gcagacctgc     3600

actggcttca gactgagacc tgtggctggc ctgctgagca gcagagactt cctggggggc     3660

ctggccttca gagtgttcca ctgcacccag tacatcagac acggcagcaa gcccatgtac     3720

acccctgagc ctgatatctg ccacgagctg ctgggccacg tgcccctgtt ctctgacaga     3780

agctttgccc agttcagcca ggagattggc ctggccagcc tgggagcccc tgatgagtat     3840

attgagaagc tggccactat ctactggttc actgtggagt ttggcctgtg caagcagggg     3900

gacagcatca aggcctatgg agctggcctg ctgagcagct ttggggagct gcagtactgc     3960

ctgtctgaga agcccaagct gctgcccctg gagctggaga agactgccat ccagaactac     4020

actgtgactg agttccagcc cctgtactat gtggctgaga gcttcaatga tgccaaggag     4080

aaggtgagaa actttgctgc caccatcccc agacccttct ctgtgagata tgacccctac     4140

acccagagaa ttgaggtgct ggacaacacc cagcagctga agatcctggc tgacagcatc     4200

aactctgaga ttggcatcct gtgctctgcc ctgcagaaga tcaagtaacc tcgagctgtg     4260

ccttctagtt gccagccatc tgttgtttgc ccctcccccg tgccttcctt gaccctggaa     4320

ggtgccactc ccactgtcct ttcctaataa aatgaggaaa ttgcatcgca ttgtctgagt     4380

aggtgtcatt ctattctggg gggtggggtg gggcaggaca gcaaggggga ggattgggaa     4440

gacaatagca ggcatgctgg ggatgcggtg ggctctatgg accggtgcgg ccgcaggaac     4500

ccctagtgat ggagttggcc actccctctc tgcgcgctcg ctcgctcact gaggccgggc     4560

gaccaaaggt cgcccgacgc ccgggctttg cccgggcggc ctcagtgagc gagcgagcgc     4620

gcagctgcct gcagg                                                      4635


<210>  19
<211>  4640
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  hPAH+truncated 2nd intron (ApoE-HCR-hAAT.hPAH-tI2.bGH) sequence

<400>  19
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc       60

gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc tgcggccgca cgcgtaggct cagaggcaca caggagtttc      180

tgggctcacc ctgccccctt ccaacccctc agttcccatc ctccagcagc tgtttgtgtg      240

ctgcctctga agtccacact gaacaaactt cagcctactc atgtccctaa aatgggcaaa      300

cattgcaagc agcaaacagc aaacacacag ccctccctgc ctgctgacct tggagctggg      360

gcagaggtca gagacctctc tgggcccatg ccacctccaa catccactcg accccttgga      420

atttcggtgg agaggagcag aggttgtcct ggcgtggttt aggtagtgtg agaggggtcg      480

acgatcttgc taccagtgga acagccacta aggattctgc agtgagagca gagggccagc      540

taagtggtac tctcccagag actgtctgac tcacgccacc ccctccacct tggacacagg      600

acgctgtggt ttctgagcca ggtacaatga ctcctttcgg taagtgcagt ggaagctgta      660

cactgcccag gcaaagcgtc cgggcagcgt aggcgggcga ctcagatccc agccagtgga      720

cttagcccct gtttgctcct ccgataactg gggtgacctt ggttaatatt caccagcagc      780

ctcccccgtt gcccctctgg atccactgct taaatacgga cgaggacagg gccctgtctc      840

ctcagcttca ggcaccacca ctgacctggg acagtgaatc agccagagac ctcactcccg      900

gggagccagc atgtccactg cggtcctgga aaacccaggc ttgggcagga aactctctga      960

ctttggacag gaaacaagct atattgaaga caactgcaat caaaatggtg ccatatcact     1020

gatcttctca ctcaaagaag aagttggtgc attggccaaa gtattgcgct tatttgaggt     1080

cagtgctaca atcatgtttg tcttggataa tgtcgtagca aacttccatg ttcttttcta     1140

gttagatgca atgaaaagaa cacaggatct ggaacaggca gatttgaatt tgagctcaag     1200

tttttacatt aaccaactgt gtgaccttag ttaagtcatt caatctctct gagcttcagt     1260

ttttccattc ataatatagt gctgataata tgtgccttgt cagtttcaac aggaactttg     1320

tgatgaaata atgtgttttg taaaatgcct aatcatatgt gtgattaggc atgattaact     1380

ataagtcata tgtgacacgt gattacattt cacataacat gtaatcacat gtgtcacatg     1440

tgattacagt taaagagtaa acaagaaata aatattaatt cttttattca ctaaattaat     1500

attgattgtc ttctatgtat aagtgtaaaa taatatgcaa gacaccgtcc ctttcttcaa     1560

gtagcttaac ccaaaactat gctttagaaa atagctaatg ttcttcaaga cattggtaaa     1620

tgtcttatga ttaaagtggt tccataatta ataaacttgg gaaattcggg catattattt     1680

tacctgattt ctttattata ggacttttag agtctataaa actaattata ctaagttgtt     1740

tacagagaga aatgtatgta ttattttcca aacttacttg actgtggatc ctttttattt     1800

taagaacatg tattcacatc tgggaacaga gtttaggaaa cgttgatttg ggtgtttgct     1860

gggcagccaa acttcacaga actccaaata ggtttcctca gccagattcc ttccgagtac     1920

tatgctaata tttttggtgg gattttgtcc cacctgaaaa tacattgctt tatgctaaga     1980

ttcctgtgac ctctctagct gattgggagg caggggtagc acattggtca gggctgtgca     2040

catacttagt gctcagtgtg tttgggcatg caatcaacaa atccttttgg ggcatgactg     2100

gatacgatta gatatcttgt gaaaacctat gatgttctca gcactgtggg tggggaggaa     2160

gatgggggac acatagaaat tgtaaggaag agaaactgcc tcctttagga tctaacaggg     2220

gaagcaaata ttctgagcag ctggggaggg aaggcagagc atgagaagtt atctcagtaa     2280

aaggtagctt tatagacatg atcttattca gtctaatgaa aataacatga ggtaggagct     2340

atttctgccc ccatttttca gagatagaaa ctgatgctta gaggggttag gtaaatgtgc     2400

ccaaggtcaa acagctagta aatacggaag aaatcattta aacccaggca ttctgagtct     2460

agaacctaca tacactctta actgctattc agtactgccc cagacagaac gggcttcata     2520

gtttgcaggg cgcagtgcaa aatgaaaacg tggggtctct tcctcaataa caggaaataa     2580

tgctgttaaa agtactaaaa tatataactt tatcctttct tctgtggtct ctctcatgtc     2640

ctgttatggt gtttttgatt tgccatttag ttgtgctctc ctcccctggg caccttggcc     2700

ctctaactgc tgggttccct gtccagccag ggctgggctg acagccaagc ccctaccaag     2760

gatggggaaa tccatcttcc atttccgtgg acctgctgca ccaacccaca gtgatgagct     2820

atcccccaag agattgtaac ctctggaatg agaatggaaa ggaagcttgc ctgaacttgg     2880

ttttaaagaa gaaaaagtaa acaacttttg caaatttaag gactttttta tactcttata     2940

aaaataattg tattcttgaa ctctccattt tgttgcgtta ggttttcctg ttctggttct     3000

gcatctttgg cctgcgttag ttccagtgac tgtctcctca ccctccccat tctctcttct     3060

aggagaatga tgtaaacctg acccacattg aatctagacc ttctcgttta aagaaagatg     3120

agtatgaatt tttcacccat ttggataaac gtagcctgcc tgctctgaca aacatcatca     3180

agatcttgag gcatgacatt ggtgccactg tccatgagct ttcacgagat aagaagaaag     3240

acacagtgcc ctggttccca agaaccattc aagagctgga cagatttgcc aatcagattc     3300

tcagctatgg agcggaactg gatgctgacc accctggttt taaagatcct gtgtaccgtg     3360

caagacggaa gcagtttgct gacattgcct acaactaccg ccatgggcag cccatccctc     3420

gagtggaata catggaggaa gaaaagaaaa catggggcac agtgttcaag actctgaagt     3480

ccttgtataa aacccatgct tgctatgagt acaatcacat ttttccactt cttgaaaagt     3540

actgtggctt ccatgaagat aacattcccc agctggaaga cgtttctcag ttcctgcaga     3600

cttgcactgg tttccgcctc cgacctgtag ctggcctgct ttcctctcgg gatttcttgg     3660

gtggcctggc cttccgagtc ttccactgca cacagtacat cagacatgga tccaagccca     3720

tgtatacccc cgaacctgac atctgccatg agctgttggg acatgtgccc ttgttttcag     3780

atcgcagctt tgcccagttt tcccaggaaa ttggccttgc ctctctgggt gcacctgatg     3840

aatacattga aaagctcgcc acaatttact ggtttactgt ggagtttggg ctctgcaaac     3900

aaggagactc cataaaggca tatggtgctg ggctcctgtc atcctttggt gaattacagt     3960

actgcttatc agagaagcca aagcttctcc ccctggagct ggagaagaca gccatccaaa     4020

attacactgt cacggagttc cagcccctgt attacgtggc agagagtttt aatgatgcca     4080

aggagaaagt aaggaacttt gctgccacaa tacctcggcc cttctcagtt cgctacgacc     4140

catacaccca aaggattgag gtcttggaca atacccagca gcttaagatt ttggctgatt     4200

ccattaacag tgaaattgga atcctttgca gtgccctcca gaaaataaag taacctcgag     4260

ctgtgccttc tagttgccag ccatctgttg tttgcccctc ccccgtgcct tccttgaccc     4320

tggaaggtgc cactcccact gtcctttcct aataaaatga ggaaattgca tcgcattgtc     4380

tgagtaggtg tcattctatt ctggggggtg gggtggggca ggacagcaag ggggaggatt     4440

gggaagacaa tagcaggcat gctggggatg cggtgggctc tatggaccgg tgcggccgca     4500

ggaaccccta gtgatggagt tggccactcc ctctctgcgc gctcgctcgc tcactgaggc     4560

cgggcgacca aaggtcgccc gacgcccggg ctttgcccgg gcggcctcag tgagcgagcg     4620

agcgcgcagc tgcctgcagg                                                 4640


<210>  20
<211>  2822
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  pFB-ApoE-hAAT-hPAH-Genius2 (vector sequence)

<400>  20
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc       60

gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc tgcggccgca cgcgtaggct cagaggcaca caggagtttc      180

tgggctcacc ctgccccctt ccaacccctc agttcccatc ctccagcagc tgtttgtgtg      240

ctgcctctga agtccacact gaacaaactt cagcctactc atgtccctaa aatgggcaaa      300

cattgcaagc agcaaacagc aaacacacag ccctccctgc ctgctgacct tggagctggg      360

gcagaggtca gagacctctc tgggcccatg ccacctccaa catccactcg accccttgga      420

atttcggtgg agaggagcag aggttgtcct ggcgtggttt aggtagtgtg agaggggtcg      480

acgatcttgc taccagtgga acagccacta aggattctgc agtgagagca gagggccagc      540

taagtggtac tctcccagag actgtctgac tcacgccacc ccctccacct tggacacagg      600

acgctgtggt ttctgagcca ggtacaatga ctcctttcgg taagtgcagt ggaagctgta      660

cactgcccag gcaaagcgtc cgggcagcgt aggcgggcga ctcagatccc agccagtgga      720

cttagcccct gtttgctcct ccgataactg gggtgacctt ggttaatatt caccagcagc      780

ctcccccgtt gcccctctgg atccactgct taaatacgga cgaggacagg gccctgtctc      840

ctcagcttca ggcaccacca ctgacctggg acagtgaatc gtaagtacta gcagctacaa      900

tccagctacc attctgcttt tattttatgg ttgggataag gctggattat tctgagtcca      960

agctaggccc ttttgctaat catgttcata cctcttatct tcctcccaca gctcctgggc     1020

aacgtgctgg tctgtgtgct ggcccatcac tttggcaaag aattgcgatc gccaccatga     1080

gcactgctgt gctggagaac cctggcctgg gcagaaagct gtctgacttt ggccaggaga     1140

ccagctacat tgaggacaac tgcaaccaga atggggccat cagcctgatc ttcagcctga     1200

aggaggaggt gggggccctg gccaaggtgc tgagactgtt tgaggagaat gatgtgaacc     1260

tgacccacat tgagagcaga cccagcagac tgaagaagga tgagtatgag ttcttcaccc     1320

acctggacaa gagaagcctg cctgccctga ccaacatcat caagatcctg agacacgata     1380

ttggggccac tgtgcacgag ctgagcagag acaagaagaa ggacactgtg ccctggttcc     1440

ccagaactat ccaggagctg gacagatttg ccaaccagat cctgagctat ggggctgagc     1500

tggatgctga ccaccctggc ttcaaggacc ctgtgtacag agccagaaga aagcagtttg     1560

ctgacattgc ctacaactac agacacggcc agcccatccc cagagtggag tacatggagg     1620

aggagaagaa gacctggggc actgtgttca agaccctgaa gagcctgtac aagacccacg     1680

cctgctatga gtacaaccac atcttccccc tgctggagaa gtactgtggc ttccacgagg     1740

acaacatccc ccagctggag gatgtgagcc agttcctgca gacctgcact ggcttcagac     1800

tgagacctgt ggctggcctg ctgagcagca gagacttcct ggggggcctg gccttcagag     1860

tgttccactg cacccagtac atcagacacg gcagcaagcc catgtacacc cctgagcctg     1920

atatctgcca cgagctgctg ggccacgtgc ccctgttctc tgacagaagc tttgcccagt     1980

tcagccagga gattggcctg gccagcctgg gggcccctga tgagtatatt gagaagctgg     2040

ccactatcta ctggttcact gtggagtttg gcctgtgcaa gcagggggac agcatcaagg     2100

cctatggggc tggcctgctg agcagctttg gggagctgca gtactgcctg tctgagaagc     2160

ccaagctgct gcccctggag ctggagaaga ctgccatcca gaactacact gtgactgagt     2220

tccagcccct gtactatgtg gctgagagct tcaatgatgc caaggagaag gtgagaaact     2280

ttgctgccac catccccaga cccttctctg tgagatacga cccctacacc cagagaattg     2340

aggtgctgga caacacccag cagctgaaga tcctggctga cagcatcaac tctgagattg     2400

gcatcctgtg ctctgccctg cagaagatca agtgacctcg agctgtgcct tctagttgcc     2460

agccatctgt tgtttgcccc tcccccgtgc cttccttgac cctggaaggt gccactccca     2520

ctgtcctttc ctaataaaat gaggaaattg catcgcattg tctgagtagg tgtcattcta     2580

ttctgggggg tggggtgggg caggacagca agggggagga ttgggaagac aatagcaggc     2640

atgctgggga tgcggtgggc tctatggacc ggtgcggccg caggaacccc tagtgatgga     2700

gttggccact ccctctctgc gcgctcgctc gctcactgag gccgggcgac caaaggtcgc     2760

ccgacgcccg ggctttgccc gggcggcctc agtgagcgag cgagcgcgca gctgcctgca     2820

gg                                                                    2822


<210>  21
<211>  2822
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  pFB-ApoE-hAAT-hPAH-JCAT (vector sequence)

<400>  21
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc       60

gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc tgcggccgca cgcgtaggct cagaggcaca caggagtttc      180

tgggctcacc ctgccccctt ccaacccctc agttcccatc ctccagcagc tgtttgtgtg      240

ctgcctctga agtccacact gaacaaactt cagcctactc atgtccctaa aatgggcaaa      300

cattgcaagc agcaaacagc aaacacacag ccctccctgc ctgctgacct tggagctggg      360

gcagaggtca gagacctctc tgggcccatg ccacctccaa catccactcg accccttgga      420

atttcggtgg agaggagcag aggttgtcct ggcgtggttt aggtagtgtg agaggggtcg      480

acgatcttgc taccagtgga acagccacta aggattctgc agtgagagca gagggccagc      540

taagtggtac tctcccagag actgtctgac tcacgccacc ccctccacct tggacacagg      600

acgctgtggt ttctgagcca ggtacaatga ctcctttcgg taagtgcagt ggaagctgta      660

cactgcccag gcaaagcgtc cgggcagcgt aggcgggcga ctcagatccc agccagtgga      720

cttagcccct gtttgctcct ccgataactg gggtgacctt ggttaatatt caccagcagc      780

ctcccccgtt gcccctctgg atccactgct taaatacgga cgaggacagg gccctgtctc      840

ctcagcttca ggcaccacca ctgacctggg acagtgaatc gtaagtacta gcagctacaa      900

tccagctacc attctgcttt tattttatgg ttgggataag gctggattat tctgagtcca      960

agctaggccc ttttgctaat catgttcata cctcttatct tcctcccaca gctcctgggc     1020

aacgtgctgg tctgtgtgct ggcccatcac tttggcaaag aattgcgatc gccaccatga     1080

gcactgctgt gctggagaac cctggcctgg gcagaaagct gtctgacttt ggccaggaga     1140

ccagctacat tgaggacaac tgcaaccaga atggggccat cagcctgatc ttcagcctga     1200

aggaggaggt gggggccctg gccaaggtgc tgagactgtt tgaggagaat gatgtgaacc     1260

tgacccacat tgagagcaga cccagcagac tgaagaagga tgagtatgag ttcttcaccc     1320

acctggacaa gagaagcctg ccagccctga ccaatattat caagatcctg aggcacgata     1380

ttggggccac agtgcacgag ctgagcagag acaagaagaa ggacacagtg ccctggttcc     1440

ccaggactat ccaggagctg gacaggtttg ccaaccagat cctgagctac ggagctgagc     1500

tggatgcaga ccaccctggc ttcaaggacc ctgtgtacag agccaggaga aagcagtttg     1560

cagatatagc ctacaactac aggcacggcc agccaatccc tagagtggag tacatggagg     1620

aggagaagaa gacctggggc actgtgttca agaccctgaa gagcctgtac aagacccacg     1680

cctgctacga gtacaaccac atcttccccc tgctggagaa gtactgtggc ttccacgagg     1740

acaacatccc ccagctggag gatgtgagcc agttcctgca gacctgcaca ggcttcaggc     1800

tgagaccagt ggcaggcctg ctgagcagca gggacttcct ggggggcctg gccttcagag     1860

tgttccactg cacccagtat atcaggcacg gcagcaagcc aatgtacacc cctgagccag     1920

atatctgcca cgagctgctg ggccacgttc ccctgttctc agacagaagc tttgcccagt     1980

tcagccagga gattggcctg gccagcctgg gggcccctga cgagtatatt gagaagctgg     2040

ccactatcta ctggttcaca gtggagtttg gcctgtgcaa gcagggggac agcatcaagg     2100

cctatggggc tggcctgctg agcagctttg gggagctgca gtactgcctg tcagagaagc     2160

caaagctgct gcccctggag ctggagaaga cagctatcca gaactacact gtgactgagt     2220

tccagcccct gtactatgtg gcagagagct tcaatgatgc caaggagaag gtgagaaact     2280

ttgctgccac catccccagg cccttctctg tgagatatga cccctacacc cagaggattg     2340

aggtgctgga caacacccag cagctgaaga tcctggcaga cagcatcaac agtgagattg     2400

gtatcctgtg ctctgccctg cagaagatca agtaacctcg agctgtgcct tctagttgcc     2460

agccatctgt tgtttgcccc tcccccgtgc cttccttgac cctggaaggt gccactccca     2520

ctgtcctttc ctaataaaat gaggaaattg catcgcattg tctgagtagg tgtcattcta     2580

ttctgggggg tggggtgggg caggacagca agggggagga ttgggaagac aatagcaggc     2640

atgctgggga tgcggtgggc tctatggacc ggtgcggccg caggaacccc tagtgatgga     2700

gttggccact ccctctctgc gcgctcgctc gctcactgag gccgggcgac caaaggtcgc     2760

ccgacgcccg ggctttgccc gggcggcctc agtgagcgag cgagcgcgca gctgcctgca     2820

gg                                                                    2822


<210>  22
<211>  2674
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  pFB-hPAHV1-TBG2uGlob (vector sequence)

<400>  22
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc       60

gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc tgcggccgca cgcgtcaggt taatttttaa aaagcagtca      180

aaagtccaag tggcccttgg cagcatttac tctctctgtt tgctctggtt aataatctca      240

ggagcacaaa cattccagat ccaggttaat ttttaaaaag cagtcaaaag tccaagtggc      300

ccttggcagc atttactctc tctgtttgct ctggttaata atctcaggag cacaaacatt      360

ccagatccgg cgcgccaggg ctggaagcta cctttgacat catttcctct gcgaatgcat      420

gtataatttc tacagaacct attagaaagg atcacccagc ctctgctttt gtacaacttt      480

cccttaaaaa actgccaatt ccactgctgt ttggcccaat agtgagaact ttttcctgct      540

gcctcttggt gcttttgcct atggccccta ttctgcctgc tgaagacact cttgccagca      600

tggacttaaa cccctccagc tctgacaatc ctctttctct tttgttttac atgaagggtc      660

tggcagccaa agcaatcact caaagttcaa accttatcat tttttgcttt gttcctcttg      720

gccttggttt tgtacatcag ctttgaaaat accatcccag ggttaatgct ggggttaatt      780

tataactaag agtgctctag ttttgcaata caggacatgc tataaaaatg gaaagatgtt      840

gctttctgag agatgcaggt ggattcttgg gcatttgctg taagtactag cagctacaat      900

ccagctacca ttctgctttt attttatggt tgggataagg ctggattatt ctgagtccaa      960

gctaggccct tttgctaatc atgttcatac ctcttatctt cctcccacag ctcctgggca     1020

acgtgctggt ctgtgtgctg gcccatcact ttggcaaaga attgcgatcg ccaccatgtc     1080

cactgcggtc ctggaaaacc caggcttggg caggaaactc tctgactttg gacaggaaac     1140

aagctatatt gaagacaact gcaatcaaaa tggtgccata tcactgatct tctcactcaa     1200

agaagaagtt ggtgcattgg ccaaagtatt gcgcttattt gaggagaatg atgtaaacct     1260

gacccacatt gaatctagac cttctcgttt aaagaaagat gagtatgaat ttttcaccca     1320

tttggataaa cgtagcctgc ctgctctgac aaacatcatc aagatcttga ggcatgacat     1380

tggtgccact gtccatgagc tttcacgaga taagaagaaa gacacagtgc cctggttccc     1440

aagaaccatt caagagctgg acagatttgc caatcagatt ctcagctatg gagcggaact     1500

ggatgctgac caccctggtt ttaaagatcc tgtgtaccgt gcaagacgga agcagtttgc     1560

tgacattgcc tacaactacc gccatgggca gcccatccct cgagtggaat acatggagga     1620

agaaaagaaa acatggggca cagtgttcaa gactctgaag tccttgtata aaacccatgc     1680

ttgctatgag tacaatcaca tttttccact tcttgaaaag tactgtggct tccatgaaga     1740

taacattccc cagctggaag acgtttctca gttcctgcag acttgcactg gtttccgcct     1800

ccgacctgta gctggcctgc tttcctctcg ggatttcttg ggtggcctgg ccttccgagt     1860

cttccactgc acacagtaca tcagacatgg atccaagccc atgtataccc ccgaacctga     1920

catctgccat gagctgttgg gacatgtgcc cttgttttca gatcgcagct ttgcccagtt     1980

ttcccaggaa attggccttg cctctctggg tgcacctgat gaatacattg aaaagctcgc     2040

cacaatttac tggtttactg tggagtttgg gctctgcaaa caaggagact ccataaaggc     2100

atatggtgct gggctcctgt catcctttgg tgaattacag tactgcttat cagagaagcc     2160

aaagcttctc cccctggagc tggagaagac agccatccaa aattacactg tcacggagtt     2220

ccagcccctg tattacgtgg cagagagttt taatgatgcc aaggagaaag taaggaactt     2280

tgctgccaca atacctcggc ccttctcagt tcgctacgac ccatacaccc aaaggattga     2340

ggtcttggac aatacccagc agcttaagat tttggctgat tccattaaca gtgaaattgg     2400

aatcctttgc agtgccctcc agaaaataaa gtaacctcga gctgtgcctt ctagttgcca     2460

gccatctgtt gtttgcccct cccccgtgcc ttccttgacc ctggaaggtg ccactcccac     2520

tgtcctttcc taataaaatg aggaaattgc atcgcattgt ctgagtaggt gtcattctat     2580

tctggggggt ggggtggggc aggacagcaa gggggaggat tgggaagaca atagcaggca     2640

tgctggggat gcggtgggct ctatggaccg gtgc                                 2674


<210>  23
<211>  2387
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  pFB-hPAHV1-TTR (vector sequence)

<400>  23
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc       60

gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc tgcggccgcg tctgtctgca catttcgtag agcgagtgtt      180

ccgatactct aatctcccta ggcaaggttc atattgactt aggttactta ttctcctttt      240

gttgactaag tcaataatca gaatcagcag gtttggagtc agcttggcag ggatcagcag      300

cctgggttgg aaggaggggg tataaaagcc ccttcaccag gagaagccgt cacacagatc      360

cacaagctcc tgacaggagg cttcccttcg actcttcctc ctttgcctcg ctggactggt      420

atttgtgtct gaagctggcc ccgcggtaag tactagcagc tacaatccag ctaccattct      480

gcttttattt tatggttggg ataaggctgg attattctga gtccaagcta ggcccttttg      540

ctaatcatgt tcatacctct tatcttcctc ccacagctcc tgggcaacgt gctggtctgt      600

gtgctggccc atcactttgg caaagaattg cgatcgccac catgtccact gcggtcctgg      660

aaaacccagg cttgggcagg aaactctctg actttggaca ggaaacaagc tatattgaag      720

acaactgcaa tcaaaatggt gccatatcac tgatcttctc actcaaagaa gaagttggtg      780

cattggccaa agtattgcgc ttatttgagg agaatgatgt aaacctgacc cacattgaat      840

ctagaccttc tcgtttaaag aaagatgagt atgaattttt cacccatttg gataaacgta      900

gcctgcctgc tctgacaaac atcatcaaga tcttgaggca tgacattggt gccactgtcc      960

atgagctttc acgagataag aagaaagaca cagtgccctg gttcccaaga accattcaag     1020

agctggacag atttgccaat cagattctca gctatggagc ggaactggat gctgaccacc     1080

ctggttttaa agatcctgtg taccgtgcaa gacggaagca gtttgctgac attgcctaca     1140

actaccgcca tgggcagccc atccctcgag tggaatacat ggaggaagaa aagaaaacat     1200

ggggcacagt gttcaagact ctgaagtcct tgtataaaac ccatgcttgc tatgagtaca     1260

atcacatttt tccacttctt gaaaagtact gtggcttcca tgaagataac attccccagc     1320

tggaagacgt ttctcagttc ctgcagactt gcactggttt ccgcctccga cctgtagctg     1380

gcctgctttc ctctcgggat ttcttgggtg gcctggcctt ccgagtcttc cactgcacac     1440

agtacatcag acatggatcc aagcccatgt atacccccga acctgacatc tgccatgagc     1500

tgttgggaca tgtgcccttg ttttcagatc gcagctttgc ccagttttcc caggaaattg     1560

gccttgcctc tctgggtgca cctgatgaat acattgaaaa gctcgccaca atttactggt     1620

ttactgtgga gtttgggctc tgcaaacaag gagactccat aaaggcatat ggtgctgggc     1680

tcctgtcatc ctttggtgaa ttacagtact gcttatcaga gaagccaaag cttctccccc     1740

tggagctgga gaagacagcc atccaaaatt acactgtcac ggagttccag cccctgtatt     1800

acgtggcaga gagttttaat gatgccaagg agaaagtaag gaactttgct gccacaatac     1860

ctcggccctt ctcagttcgc tacgacccat acacccaaag gattgaggtc ttggacaata     1920

cccagcagct taagattttg gctgattcca ttaacagtga aattggaatc ctttgcagtg     1980

ccctccagaa aataaagtaa cctcgagctg tgccttctag ttgccagcca tctgttgttt     2040

gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac tcccactgtc ctttcctaat     2100

aaaatgagga aattgcatcg cattgtctga gtaggtgtca ttctattctg gggggtgggg     2160

tggggcagga cagcaagggg gaggattggg aagacaatag caggcatgct ggggatgcgg     2220

tgggctctat ggaccggtgc ggccgcagga acccctagtg atggagttgg ccactccctc     2280

tctgcgcgct cgctcgctca ctgaggccgg gcgaccaaag gtcgcccgac gcccgggctt     2340

tgcccgggcg gcctcagtga gcgagcgagc gcgcagctgc ctgcagg                   2387


