                         SEQUENCE LISTING

<110>  THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE 
       SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
 
<120>  GENE THERAPY FOR COMBINED METHYLMALONIC ACIDEMIA/ACIDURIA AND 
       HYPERHOMOCYSTEINEMIA/HOMOCYSTINURIA, COBALAMIN C TYPE, AND 
       DEFICIENCY OF MMACHC

<130>  723684

<150>  US 62/279,285
<151>  2016-01-15

<150>  US 62/266,352
<151>  2015-12-11

<160>  12    

<170>  PatentIn version 3.5

<210>  1
<211>  846
<212>  DNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<223>  wild-type human MMACHC

<400>  1
atggagccga aagtcgcaga gctgaagcag aagatcgagg acacgctatg tccttttggc       60

ttcgaggttt accccttcca ggtggcatgg tacaatgaac tcttgcctcc agccttccac      120

ctaccgctgc caggacctac cctggccttc ctggtactca gcacgcctgc catgtttgac      180

cgggccctca agcccttctt gcagagctgc cacctccgaa tgctgactga cccagtggac      240

cagtgtgtgg cctaccatct gggccgtgtt agagagagcc tcccagagct gcagatagaa      300

atcattgctg actacgaggt gcaccccaac cgacgcccca agatcctggc ccagacagca      360

gcccatgtag ctggggctgc ttactactac caacgacaag atgtggaggc tgacccatgg      420

gggaaccagc gcatatcagg tgtgtgcata cacccccgat ttgggggctg gtttgccatc      480

cgaggggtag tgctgctgcc agggatagag gtgccagatc tgccacccag aaaacctcat      540

gactgtgtac ctacaagagc tgaccgtatc gccctactcg aaggcttcaa tttccactgg      600

cgtgattgga cttaccggga tgctgtgaca ccccaggagc gctactcaga agagcagaag      660

gcctacttct ccactccacc tgcccaacga ttggccctat tgggcttggc tcagccctca      720

gagaagccta gttctccctc cccggacctt ccctttacca cacccgcccc caagaagcct      780

gggaatccca gcagagcccg gagctggctc agccccaggg tctcaccacc tgcatcccct      840

ggccct                                                                 846


<210>  2
<211>  846
<212>  DNA
<213>  Homo sapiens


<220>
<221>  misc_feature
<223>  codon optimized human MMACHC

<400>  2
atggaaccta aagtcgcaga actcaagcag aagatcgagg acaccctgtg cccgttcgga       60

ttcgaggtgt accctttcca agtggcctgg tacaacgagc tcctgccccc tgctttccat      120

ttgccactgc ccggtccgac tctcgcgttt cttgtgctgt cgacccccgc gatgttcgac      180

cgcgccctca agccgttcct gcaatcatgt catctgcgga tgctgaccga tccggtcgat      240

cagtgcgtgg cctaccacct gggtcgcgtc agggaatccc tgccggagct tcagatcgag      300

atcatcgcgg attacgaagt gcacccaaac cggcggccca agattctcgc ccaaaccgcc      360

gcgcacgtgg ctggcgccgc ctattactac cagcgccagg acgtcgaggc ggacccttgg      420

ggcaatcaga gaatctctgg agtgtgcatc cacccacggt tcgggggatg gttcgcaatt      480

cggggcgtgg tgctgctgcc gggaatcgag gtgccagact tgcctcctcg aaagccccac      540

gactgcgtgc caactagagc cgatagaatt gccctgctgg aagggttcaa cttccattgg      600

cgcgactgga cctaccggga cgctgtgact cctcaagaac gctacagcga agaacagaag      660

gcctactttt caactccgcc ggcccagcgc ctggcactcc tgggactggc ccagccctcc      720

gagaagccta gctccccctc gccggacttg cccttcacca ccccggcccc caaaaagccc      780

ggcaacccta gccgggccag gtcctggctg tccccgaggg tgtccccgcc tgcctccccc      840

ggccct                                                                 846


<210>  3
<211>  27
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  hemagglutinin (HA) tag

<400>  3
tacccgtatg atgtgcccga ctacgcc                                           27


<210>  4
<211>  81
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  3xFLAG tag

<400>  4
gactacaaag atgacgacga caagggagac tataaggacg acgacgataa gggagattac       60

aaggatgacg atgacaaggg c                                                 81


<210>  5
<211>  6037
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  AAV with wild-type human MMACHC

<400>  5
gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc gggcgacctt       60

tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca actccatcac      120

taggggttcc ttgtagttaa tgattaaccc gccatgctac ttatctacca gggtaatggg      180

gatcctctag aactatagct agtcgacatt gattattgac tagttattaa tagtaatcaa      240

ttacggggtc attagttcat agcccatata tggagttccg cgttacataa cttacggtaa      300

atggcccgcc tggctgaccg cccaacgacc cccgcccatt gacgtcaata atgacgtatg      360

ttcccatagt aacgccaata gggactttcc attgacgtca atgggtggag tatttacggt      420

aaactgccca cttggcagta catcaagtgt atcatatgcc aagtacgccc cctattgacg      480

tcaatgacgg taaatggccc gcctggcatt atgcccagta catgacctta tgggactttc      540

ctacttggca gtacatctac gtattagtca tcgctattac catggtcgag gtgagcccca      600

cgttctgctt cactctcccc atctcccccc cctccccacc cccaattttg tatttattta      660

ttttttaatt attttgtgca gcgatggggg cggggggggg gggggggcgc gcgccaggcg      720

gggcggggcg gggcgagggg cggggcgggg cgaggcggag aggtgcggcg gcagccaatc      780

agagcggcgc gctccgaaag tttcctttta tggcgaggcg gcggcggcgg cggccctata      840

aaaagcgaag cgcgcggcgg gcgggagtcg ctgcgcgctg ccttcgcccc gtgccccgct      900

ccgccgccgc ctcgcgccgc ccgccccggc tctgactgac cgcgttactc ccacaggtga      960

gcgggcggga cggcccttct cctccgggct gtaattagcg cttggtttaa tgacggcttg     1020

tttcttttct gtggctgcgt gaaagccttg aggggctccg ggagggccct ttgtgcgggg     1080

ggagcggctc ggggggtgcg tgcgtgtgtg tgtgcgtggg gagcgccgcg tgcggctccg     1140

cgctgcccgg cggctgtgag cgctgcgggc gcggcgcggg gctttgtgcg ctccgcagtg     1200

tgcgcgaggg gagcgcggcc gggggcggtg ccccgcggtg cggggggggc tgcgagggga     1260

acaaaggctg cgtgcggggt gtgtgcgtgg gggggtgagc agggggtgtg ggcgcgtcgg     1320

tcgggctgca accccccctg cacccccctc cccgagttgc tgagcacggc ccggcttcgg     1380

gtgcggggct ccgtacgggg cgtggcgcgg ggctcgccgt gccgggcggg gggtggcggc     1440

aggtgggggt gccgggcggg gcggggccgc ctcgggccgg ggagggctcg ggggaggggc     1500

gcggcggccc ccggagcgcc ggcggctgtc gaggcgcggc gagccgcagc cattgccttt     1560

tatggtaatc gtgcgagagg gcgcagggac ttcctttgtc ccaaatctgt gcggagccga     1620

aatctgggag gcgccgccgc accccctcta gcgggcgcgg ggcgaagcgg tgcggcgccg     1680

gcaggaagga aatgggcggg gagggccttc gtgcgtcgcc gcgccgccgt ccccttctcc     1740

ctctccagcc tcggggctgt ccgcgggggg acggctgcct tcggggggga cggggcaggg     1800

cggggttcgg cttctggcgt gtgaccggcg gctctagagc ctctgctaac catgttcatg     1860

ccttcttctt tttcctacag ctcctgggca acgtgctggt tattgtgctg tctcatcatt     1920

ttggcaaaga attcgtcgac tggatccggt accgaggaga tctgccgccg cgatcgccat     1980

ggagccgaaa gtcgcagagc tgaagcagaa gatcgaggac acgctatgtc cttttggctt     2040

cgaggtttac cccttccagg tggcatggta caatgaactc ttgcctccag ccttccacct     2100

accgctgcca ggacctaccc tggccttcct ggtactcagc acgcctgcca tgtttgaccg     2160

ggccctcaag cccttcttgc agagctgcca cctccgaatg ctgactgacc cagtggacca     2220

gtgtgtggcc taccatctgg gccgtgttag agagagcctc ccagagctgc agatagaaat     2280

cattgctgac tacgaggtgc accccaaccg acgccccaag atcctggccc agacagcagc     2340

ccatgtagct ggggctgctt actactacca acgacaagat gtggaggctg acccatgggg     2400

gaaccagcgc atatcaggtg tgtgcataca cccccgattt gggggctggt ttgccatccg     2460

aggggtagtg ctgctgccag ggatagaggt gccagatctg ccacccagaa aacctcatga     2520

ctgtgtacct acaagagctg accgtatcgc cctactcgaa ggcttcaatt tccactggcg     2580

tgattggact taccgggatg ctgtgacacc ccaggagcgc tactcagaag agcagaaggc     2640

ctacttctcc actccacctg cccaacgatt ggccctattg ggcttggctc agccctcaga     2700

gaagcctagt tctccctccc cggaccttcc ctttaccaca cccgccccca agaagcctgg     2760

gaatcccagc agagcccgga gctggctcag ccccagggtc tcaccacctg catcccctgg     2820

ccctacgcgt acgcggccgc tcgaggacgg ggtgaactac gcctgaggat ccgatctttt     2880

tccctctgcc aaaaattatg gggacatcat gaagcccctt gagcatctga cttctggcta     2940

ataaaggaaa tttattttca ttgcaatagt gtgttggaat tttttgtgtc tctcactcgg     3000

aagcaattcg ttgatctgaa tttcgaccac ccataatacc cattaccctg gtagataagt     3060

agcatggcgg gttaatcatt aactacaagg aacccctagt gatggagttg gccactccct     3120

ctctgcgcgc tcgctcgctc actgaggccg ggcgaccaaa ggtcgcccga cgcccgggct     3180

ttgcccgggc ggcctcagtg agcgagcgag cgcgcagcct taattaacct aattcactgg     3240

ccgtcgtttt acaacgtcgt gactgggaaa accctggcgt tacccaactt aatcgccttg     3300

cagcacatcc ccctttcgcc agctggcgta atagcgaaga ggcccgcacc gatcgccctt     3360

cccaacagtt gcgcagcctg aatggcgaat gggacgcgcc ctgtagcggc gcattaagcg     3420

cggcgggtgt ggtggttacg cgcagcgtga ccgctacact tgccagcgcc ctagcgcccg     3480

ctcctttcgc tttcttccct tcctttctcg ccacgttcgc cggctttccc cgtcaagctc     3540

taaatcgggg gctcccttta gggttccgat ttagtgcttt acggcacctc gaccccaaaa     3600

aacttgatta gggtgatggt tcacgtagtg ggccatcgcc ctgatagacg gtttttcgcc     3660

ctttgacgtt ggagtccacg ttctttaata gtggactctt gttccaaact ggaacaacac     3720

tcaaccctat ctcggtctat tcttttgatt tataagggat tttgccgatt tcggcctatt     3780

ggttaaaaaa tgagctgatt taacaaaaat ttaacgcgaa ttttaacaaa atattaacgc     3840

ttacaattta ggtggcactt ttcggggaaa tgtgcgcgga acccctattt gtttattttt     3900

ctaaatacat tcaaatatgt atccgctcat gagacaataa ccctgataaa tgcttcaata     3960

atattgaaaa aggaagagta tgagtattca acatttccgt gtcgccctta ttcccttttt     4020

tgcggcattt tgccttcctg tttttgctca cccagaaacg ctggtgaaag taaaagatgc     4080

tgaagatcag ttgggtgcac gagtgggtta catcgaactg gatctcaaca gcggtaagat     4140

ccttgagagt tttcgccccg aagaacgttt tccaatgatg agcactttta aagttctgct     4200

atgtggcgcg gtattatccc gtattgacgc cgggcaagag caactcggtc gccgcataca     4260

ctattctcag aatgacttgg ttgagtactc accagtcaca gaaaagcatc ttacggatgg     4320

catgacagta agagaattat gcagtgctgc cataaccatg agtgataaca ctgcggccaa     4380

cttacttctg acaacgatcg gaggaccgaa ggagctaacc gcttttttgc acaacatggg     4440

ggatcatgta actcgccttg atcgttggga accggagctg aatgaagcca taccaaacga     4500

cgagcgtgac accacgatgc ctgtagcaat ggcaacaacg ttgcgcaaac tattaactgg     4560

cgaactactt actctagctt cccggcaaca attaatagac tggatggagg cggataaagt     4620

tgcaggacca cttctgcgct cggcccttcc ggctggctgg tttattgctg ataaatctgg     4680

agccggtgag cgtgggtctc gcggtatcat tgcagcactg gggccagatg gtaagccctc     4740

ccgtatcgta gttatctaca cgacggggag tcaggcaact atggatgaac gaaatagaca     4800

gatcgctgag ataggtgcct cactgattaa gcattggtaa ctgtcagacc aagtttactc     4860

atatatactt tagattgatt taaaacttca tttttaattt aaaaggatct aggtgaagat     4920

cctttttgat aatctcatga ccaaaatccc ttaacgtgag ttttcgttcc actgagcgtc     4980

agaccccgta gaaaagatca aaggatcttc ttgagatcct ttttttctgc gcgtaatctg     5040

ctgcttgcaa acaaaaaaac caccgctacc agcggtggtt tgtttgccgg atcaagagct     5100

accaactctt tttccgaagg taactggctt cagcagagcg cagataccaa atactgttct     5160

tctagtgtag ccgtagttag gccaccactt caagaactct gtagcaccgc ctacatacct     5220

cgctctgcta atcctgttac cagtggctgc tgccagtggc gataagtcgt gtcttaccgg     5280

gttggactca agacgatagt taccggataa ggcgcagcgg tcgggctgaa cggggggttc     5340

gtgcacacag cccagcttgg agcgaacgac ctacaccgaa ctgagatacc tacagcgtga     5400

gctatgagaa agcgccacgc ttcccgaagg gagaaaggcg gacaggtatc cggtaagcgg     5460

cagggtcgga acaggagagc gcacgaggga gcttccaggg ggaaacgcct ggtatcttta     5520

tagtcctgtc gggtttcgcc acctctgact tgagcgtcga tttttgtgat gctcgtcagg     5580

ggggcggagc ctatggaaaa acgccagcaa cgcggccttt ttacggttcc tggccttttg     5640

ctggcctttt gctcacatgt tctttcctgc gttatcccct gattctgtgg ataaccgtat     5700

taccgccttt gagtgagctg ataccgctcg ccgcagccga acgaccgagc gcagcgagtc     5760

agtgagcgag gaagcggaag agcgcccaat acgcaaaccg cctctccccg cgcgttggcc     5820

gattcattaa tgcagctggc acgacaggtt tcccgactgg aaagcgggca gtgagcgcaa     5880

cgcaattaat gtgagttagc tcactcatta ggcaccccag gctttacact ttatgcttcc     5940

ggctcgtatg ttgtgtggaa ttgtgagcgg ataacaattt cacacaggaa acagctatga     6000

ccatgattac gccagattta attaaggcct taattag                              6037


<210>  6
<211>  6007
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  AAV with wild-type mouse Mmachc

<400>  6
gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc gggcgacctt       60

tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca actccatcac      120

taggggttcc ttgtagttaa tgattaaccc gccatgctac ttatctacca gggtaatggg      180

gatcctctag aactatagct agtcgacatt gattattgac tagttattaa tagtaatcaa      240

ttacggggtc attagttcat agcccatata tggagttccg cgttacataa cttacggtaa      300

atggcccgcc tggctgaccg cccaacgacc cccgcccatt gacgtcaata atgacgtatg      360

ttcccatagt aacgccaata gggactttcc attgacgtca atgggtggag tatttacggt      420

aaactgccca cttggcagta catcaagtgt atcatatgcc aagtacgccc cctattgacg      480

tcaatgacgg taaatggccc gcctggcatt atgcccagta catgacctta tgggactttc      540

ctacttggca gtacatctac gtattagtca tcgctattac catggtcgag gtgagcccca      600

cgttctgctt cactctcccc atctcccccc cctccccacc cccaattttg tatttattta      660

ttttttaatt attttgtgca gcgatggggg cggggggggg gggggggcgc gcgccaggcg      720

gggcggggcg gggcgagggg cggggcgggg cgaggcggag aggtgcggcg gcagccaatc      780

agagcggcgc gctccgaaag tttcctttta tggcgaggcg gcggcggcgg cggccctata      840

aaaagcgaag cgcgcggcgg gcgggagtcg ctgcgcgctg ccttcgcccc gtgccccgct      900

ccgccgccgc ctcgcgccgc ccgccccggc tctgactgac cgcgttactc ccacaggtga      960

gcgggcggga cggcccttct cctccgggct gtaattagcg cttggtttaa tgacggcttg     1020

tttcttttct gtggctgcgt gaaagccttg aggggctccg ggagggccct ttgtgcgggg     1080

ggagcggctc ggggggtgcg tgcgtgtgtg tgtgcgtggg gagcgccgcg tgcggctccg     1140

cgctgcccgg cggctgtgag cgctgcgggc gcggcgcggg gctttgtgcg ctccgcagtg     1200

tgcgcgaggg gagcgcggcc gggggcggtg ccccgcggtg cggggggggc tgcgagggga     1260

acaaaggctg cgtgcggggt gtgtgcgtgg gggggtgagc agggggtgtg ggcgcgtcgg     1320

tcgggctgca accccccctg cacccccctc cccgagttgc tgagcacggc ccggcttcgg     1380

gtgcggggct ccgtacgggg cgtggcgcgg ggctcgccgt gccgggcggg gggtggcggc     1440

aggtgggggt gccgggcggg gcggggccgc ctcgggccgg ggagggctcg ggggaggggc     1500

gcggcggccc ccggagcgcc ggcggctgtc gaggcgcggc gagccgcagc cattgccttt     1560

tatggtaatc gtgcgagagg gcgcagggac ttcctttgtc ccaaatctgt gcggagccga     1620

aatctgggag gcgccgccgc accccctcta gcgggcgcgg ggcgaagcgg tgcggcgccg     1680

gcaggaagga aatgggcggg gagggccttc gtgcgtcgcc gcgccgccgt ccccttctcc     1740

ctctccagcc tcggggctgt ccgcgggggg acggctgcct tcggggggga cggggcaggg     1800

cggggttcgg cttctggcgt gtgaccggcg gctctagagc ctctgctaac catgttcatg     1860

ccttcttctt tttcctacag ctcctgggca acgtgctggt tattgtgctg tctcatcatt     1920

ttggcaaaga attcgccctt agccccggga gatctttcag cgtgcgttat ggagccgcga     1980

gtcgcagagc tgaagcagaa gattgaggac accttgtgtc cttttggctt cgaagtttat     2040

cccttccagg tggcgtggta caatgaactc ctgcctccag ccttccactt gcccttccca     2100

ggacctaccc tggccttcct ggtactcagc acacctgcta tgtttgacag agccctcaaa     2160

cccttcttaa agagctgcca cttccaaaca ctgagagacc cggtggatca atgtgtgtcc     2220

taccacctga ggagtgttac agagaagttt ccagaagtgc atatggaagt cattgctgac     2280

tatgaggtac accccaatcg gcgacctaag attctcgccc agacagcagc ccatgtggca     2340

ggtgctgctt attactacca acgacaagat gtggatgcag acccatgggg gacccagcac     2400

atagcaggtg tgtgcataca cccccgattt gggggctggt ttgccatccg aggggttatg     2460

ttgctgccag ggattgaagt gccaaatttg ccacccagaa agccccctga ctgtgtgcct     2520

acaagagctg gccgcatcac tctgcttgaa ggtttcaatt tccattggcg ggactggact     2580

taccgtgatg ctgtgactcc tgaagaacgg tactccgaag aacagaagat ctacttttcc     2640

accccacctg cccaacgctt ggccctatta ggcttagccc aaccctcaga acaccctagc     2700

actacatctg agcttcctct ttccttgctt actaaacctc agaattccag gagagctcga     2760

agctggctga gtccaagtgt ctcaccacct gtatccccag gcccttgatc tcgaggacgg     2820

ggtgaactac gcctgaggat ccgatctttt tccctctgcc aaaaattatg gggacatcat     2880

gaagcccctt gagcatctga cttctggcta ataaaggaaa tttattttca ttgcaatagt     2940

gtgttggaat tttttgtgtc tctcactcgg aagcaattcg ttgatctgaa tttcgaccac     3000

ccataatacc cattaccctg gtagataagt agcatggcgg gttaatcatt aactacaagg     3060

aacccctagt gatggagttg gccactccct ctctgcgcgc tcgctcgctc actgaggccg     3120

ggcgaccaaa ggtcgcccga cgcccgggct ttgcccgggc ggcctcagtg agcgagcgag     3180

cgcgcagcct taattaacct aattcactgg ccgtcgtttt acaacgtcgt gactgggaaa     3240

accctggcgt tacccaactt aatcgccttg cagcacatcc ccctttcgcc agctggcgta     3300

atagcgaaga ggcccgcacc gatcgccctt cccaacagtt gcgcagcctg aatggcgaat     3360

gggacgcgcc ctgtagcggc gcattaagcg cggcgggtgt ggtggttacg cgcagcgtga     3420

ccgctacact tgccagcgcc ctagcgcccg ctcctttcgc tttcttccct tcctttctcg     3480

ccacgttcgc cggctttccc cgtcaagctc taaatcgggg gctcccttta gggttccgat     3540

ttagtgcttt acggcacctc gaccccaaaa aacttgatta gggtgatggt tcacgtagtg     3600

ggccatcgcc ctgatagacg gtttttcgcc ctttgacgtt ggagtccacg ttctttaata     3660

gtggactctt gttccaaact ggaacaacac tcaaccctat ctcggtctat tcttttgatt     3720

tataagggat tttgccgatt tcggcctatt ggttaaaaaa tgagctgatt taacaaaaat     3780

ttaacgcgaa ttttaacaaa atattaacgc ttacaattta ggtggcactt ttcggggaaa     3840

tgtgcgcgga acccctattt gtttattttt ctaaatacat tcaaatatgt atccgctcat     3900

gagacaataa ccctgataaa tgcttcaata atattgaaaa aggaagagta tgagtattca     3960

acatttccgt gtcgccctta ttcccttttt tgcggcattt tgccttcctg tttttgctca     4020

cccagaaacg ctggtgaaag taaaagatgc tgaagatcag ttgggtgcac gagtgggtta     4080

catcgaactg gatctcaaca gcggtaagat ccttgagagt tttcgccccg aagaacgttt     4140

tccaatgatg agcactttta aagttctgct atgtggcgcg gtattatccc gtattgacgc     4200

cgggcaagag caactcggtc gccgcataca ctattctcag aatgacttgg ttgagtactc     4260

accagtcaca gaaaagcatc ttacggatgg catgacagta agagaattat gcagtgctgc     4320

cataaccatg agtgataaca ctgcggccaa cttacttctg acaacgatcg gaggaccgaa     4380

ggagctaacc gcttttttgc acaacatggg ggatcatgta actcgccttg atcgttggga     4440

accggagctg aatgaagcca taccaaacga cgagcgtgac accacgatgc ctgtagcaat     4500

ggcaacaacg ttgcgcaaac tattaactgg cgaactactt actctagctt cccggcaaca     4560

attaatagac tggatggagg cggataaagt tgcaggacca cttctgcgct cggcccttcc     4620

ggctggctgg tttattgctg ataaatctgg agccggtgag cgtgggtctc gcggtatcat     4680

tgcagcactg gggccagatg gtaagccctc ccgtatcgta gttatctaca cgacggggag     4740

tcaggcaact atggatgaac gaaatagaca gatcgctgag ataggtgcct cactgattaa     4800

gcattggtaa ctgtcagacc aagtttactc atatatactt tagattgatt taaaacttca     4860

tttttaattt aaaaggatct aggtgaagat cctttttgat aatctcatga ccaaaatccc     4920

ttaacgtgag ttttcgttcc actgagcgtc agaccccgta gaaaagatca aaggatcttc     4980

ttgagatcct ttttttctgc gcgtaatctg ctgcttgcaa acaaaaaaac caccgctacc     5040

agcggtggtt tgtttgccgg atcaagagct accaactctt tttccgaagg taactggctt     5100

cagcagagcg cagataccaa atactgttct tctagtgtag ccgtagttag gccaccactt     5160

caagaactct gtagcaccgc ctacatacct cgctctgcta atcctgttac cagtggctgc     5220

tgccagtggc gataagtcgt gtcttaccgg gttggactca agacgatagt taccggataa     5280

ggcgcagcgg tcgggctgaa cggggggttc gtgcacacag cccagcttgg agcgaacgac     5340

ctacaccgaa ctgagatacc tacagcgtga gctatgagaa agcgccacgc ttcccgaagg     5400

gagaaaggcg gacaggtatc cggtaagcgg cagggtcgga acaggagagc gcacgaggga     5460

gcttccaggg ggaaacgcct ggtatcttta tagtcctgtc gggtttcgcc acctctgact     5520

tgagcgtcga tttttgtgat gctcgtcagg ggggcggagc ctatggaaaa acgccagcaa     5580

cgcggccttt ttacggttcc tggccttttg ctggcctttt gctcacatgt tctttcctgc     5640

gttatcccct gattctgtgg ataaccgtat taccgccttt gagtgagctg ataccgctcg     5700

ccgcagccga acgaccgagc gcagcgagtc agtgagcgag gaagcggaag agcgcccaat     5760

acgcaaaccg cctctccccg cgcgttggcc gattcattaa tgcagctggc acgacaggtt     5820

tcccgactgg aaagcgggca gtgagcgcaa cgcaattaat gtgagttagc tcactcatta     5880

ggcaccccag gctttacact ttatgcttcc ggctcgtatg ttgtgtggaa ttgtgagcgg     5940

ataacaattt cacacaggaa acagctatga ccatgattac gccagattta attaaggcct     6000

taattag                                                               6007


<210>  7
<211>  6005
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  AAV with human codon optimized MMACHC

<400>  7
gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc gggcgacctt       60

tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca actccatcac      120

taggggttcc ttgtagttaa tgattaaccc gccatgctac ttatctacca gggtaatggg      180

gatcctctag aactatagct agtcgacatt gattattgac tagttattaa tagtaatcaa      240

ttacggggtc attagttcat agcccatata tggagttccg cgttacataa cttacggtaa      300

atggcccgcc tggctgaccg cccaacgacc cccgcccatt gacgtcaata atgacgtatg      360

ttcccatagt aacgccaata gggactttcc attgacgtca atgggtggag tatttacggt      420

aaactgccca cttggcagta catcaagtgt atcatatgcc aagtacgccc cctattgacg      480

tcaatgacgg taaatggccc gcctggcatt atgcccagta catgacctta tgggactttc      540

ctacttggca gtacatctac gtattagtca tcgctattac catggtcgag gtgagcccca      600

cgttctgctt cactctcccc atctcccccc cctccccacc cccaattttg tatttattta      660

ttttttaatt attttgtgca gcgatggggg cggggggggg gggggggcgc gcgccaggcg      720

gggcggggcg gggcgagggg cggggcgggg cgaggcggag aggtgcggcg gcagccaatc      780

agagcggcgc gctccgaaag tttcctttta tggcgaggcg gcggcggcgg cggccctata      840

aaaagcgaag cgcgcggcgg gcgggagtcg ctgcgcgctg ccttcgcccc gtgccccgct      900

ccgccgccgc ctcgcgccgc ccgccccggc tctgactgac cgcgttactc ccacaggtga      960

gcgggcggga cggcccttct cctccgggct gtaattagcg cttggtttaa tgacggcttg     1020

tttcttttct gtggctgcgt gaaagccttg aggggctccg ggagggccct ttgtgcgggg     1080

ggagcggctc ggggggtgcg tgcgtgtgtg tgtgcgtggg gagcgccgcg tgcggctccg     1140

cgctgcccgg cggctgtgag cgctgcgggc gcggcgcggg gctttgtgcg ctccgcagtg     1200

tgcgcgaggg gagcgcggcc gggggcggtg ccccgcggtg cggggggggc tgcgagggga     1260

acaaaggctg cgtgcggggt gtgtgcgtgg gggggtgagc agggggtgtg ggcgcgtcgg     1320

tcgggctgca accccccctg cacccccctc cccgagttgc tgagcacggc ccggcttcgg     1380

gtgcggggct ccgtacgggg cgtggcgcgg ggctcgccgt gccgggcggg gggtggcggc     1440

aggtgggggt gccgggcggg gcggggccgc ctcgggccgg ggagggctcg ggggaggggc     1500

gcggcggccc ccggagcgcc ggcggctgtc gaggcgcggc gagccgcagc cattgccttt     1560

tatggtaatc gtgcgagagg gcgcagggac ttcctttgtc ccaaatctgt gcggagccga     1620

aatctgggag gcgccgccgc accccctcta gcgggcgcgg ggcgaagcgg tgcggcgccg     1680

gcaggaagga aatgggcggg gagggccttc gtgcgtcgcc gcgccgccgt ccccttctcc     1740

ctctccagcc tcggggctgt ccgcgggggg acggctgcct tcggggggga cggggcaggg     1800

cggggttcgg cttctggcgt gtgaccggcg gctctagagc ctctgctaac catgttcatg     1860

ccttcttctt tttcctacag ctcctgggca acgtgctggt tattgtgctg tctcatcatt     1920

ttggcaaaga attcgatatc gccgccacca tggaacctaa agtcgcagaa ctcaagcaga     1980

agatcgagga caccctgtgc ccgttcggat tcgaggtgta ccctttccaa gtggcctggt     2040

acaacgagct cctgccccct gctttccatt tgccactgcc cggtccgact ctcgcgtttc     2100

ttgtgctgtc gacccccgcg atgttcgacc gcgccctcaa gccgttcctg caatcatgtc     2160

atctgcggat gctgaccgat ccggtcgatc agtgcgtggc ctaccacctg ggtcgcgtca     2220

gggaatccct gccggagctt cagatcgaga tcatcgcgga ttacgaagtg cacccaaacc     2280

ggcggcccaa gattctcgcc caaaccgccg cgcacgtggc tggcgccgcc tattactacc     2340

agcgccagga cgtcgaggcg gacccttggg gcaatcagag aatctctgga gtgtgcatcc     2400

acccacggtt cgggggatgg ttcgcaattc ggggcgtggt gctgctgccg ggaatcgagg     2460

tgccagactt gcctcctcga aagccccacg actgcgtgcc aactagagcc gatagaattg     2520

ccctgctgga agggttcaac ttccattggc gcgactggac ctaccgggac gctgtgactc     2580

ctcaagaacg ctacagcgaa gaacagaagg cctacttttc aactccgccg gcccagcgcc     2640

tggcactcct gggactggcc cagccctccg agaagcctag ctccccctcg ccggacttgc     2700

ccttcaccac cccggccccc aaaaagcccg gcaaccctag ccgggccagg tcctggctgt     2760

ccccgagggt gtccccgcct gcctcccccg gcccttaatg aaagcttctc gaggacgggg     2820

tgaactacgc ctgaggatcc gatctttttc cctctgccaa aaattatggg gacatcatga     2880

agccccttga gcatctgact tctggctaat aaaggaaatt tattttcatt gcaatagtgt     2940

gttggaattt tttgtgtctc tcactcggaa gcaattcgtt gatctgaatt tcgaccaccc     3000

ataataccca ttaccctggt agataagtag catggcgggt taatcattaa ctacaaggaa     3060

cccctagtga tggagttggc cactccctct ctgcgcgctc gctcgctcac tgaggccggg     3120

cgaccaaagg tcgcccgacg cccgggcttt gcccgggcgg cctcagtgag cgagcgagcg     3180

cgcagcctta attaacctaa ttcactggcc gtcgttttac aacgtcgtga ctgggaaaac     3240

cctggcgtta cccaacttaa tcgccttgca gcacatcccc ctttcgccag ctggcgtaat     3300

agcgaagagg cccgcaccga tcgcccttcc caacagttgc gcagcctgaa tggcgaatgg     3360

gacgcgccct gtagcggcgc attaagcgcg gcgggtgtgg tggttacgcg cagcgtgacc     3420

gctacacttg ccagcgccct agcgcccgct cctttcgctt tcttcccttc ctttctcgcc     3480

acgttcgccg gctttccccg tcaagctcta aatcgggggc tccctttagg gttccgattt     3540

agtgctttac ggcacctcga ccccaaaaaa cttgattagg gtgatggttc acgtagtggg     3600

ccatcgccct gatagacggt ttttcgccct ttgacgttgg agtccacgtt ctttaatagt     3660

ggactcttgt tccaaactgg aacaacactc aaccctatct cggtctattc ttttgattta     3720

taagggattt tgccgatttc ggcctattgg ttaaaaaatg agctgattta acaaaaattt     3780

aacgcgaatt ttaacaaaat attaacgctt acaatttagg tggcactttt cggggaaatg     3840

tgcgcggaac ccctatttgt ttatttttct aaatacattc aaatatgtat ccgctcatga     3900

gacaataacc ctgataaatg cttcaataat attgaaaaag gaagagtatg agtattcaac     3960

atttccgtgt cgcccttatt cccttttttg cggcattttg ccttcctgtt tttgctcacc     4020

cagaaacgct ggtgaaagta aaagatgctg aagatcagtt gggtgcacga gtgggttaca     4080

tcgaactgga tctcaacagc ggtaagatcc ttgagagttt tcgccccgaa gaacgttttc     4140

caatgatgag cacttttaaa gttctgctat gtggcgcggt attatcccgt attgacgccg     4200

ggcaagagca actcggtcgc cgcatacact attctcagaa tgacttggtt gagtactcac     4260

cagtcacaga aaagcatctt acggatggca tgacagtaag agaattatgc agtgctgcca     4320

taaccatgag tgataacact gcggccaact tacttctgac aacgatcgga ggaccgaagg     4380

agctaaccgc ttttttgcac aacatggggg atcatgtaac tcgccttgat cgttgggaac     4440

cggagctgaa tgaagccata ccaaacgacg agcgtgacac cacgatgcct gtagcaatgg     4500

caacaacgtt gcgcaaacta ttaactggcg aactacttac tctagcttcc cggcaacaat     4560

taatagactg gatggaggcg gataaagttg caggaccact tctgcgctcg gcccttccgg     4620

ctggctggtt tattgctgat aaatctggag ccggtgagcg tgggtctcgc ggtatcattg     4680

cagcactggg gccagatggt aagccctccc gtatcgtagt tatctacacg acggggagtc     4740

aggcaactat ggatgaacga aatagacaga tcgctgagat aggtgcctca ctgattaagc     4800

attggtaact gtcagaccaa gtttactcat atatacttta gattgattta aaacttcatt     4860

tttaatttaa aaggatctag gtgaagatcc tttttgataa tctcatgacc aaaatccctt     4920

aacgtgagtt ttcgttccac tgagcgtcag accccgtaga aaagatcaaa ggatcttctt     4980

gagatccttt ttttctgcgc gtaatctgct gcttgcaaac aaaaaaacca ccgctaccag     5040

cggtggtttg tttgccggat caagagctac caactctttt tccgaaggta actggcttca     5100

gcagagcgca gataccaaat actgttcttc tagtgtagcc gtagttaggc caccacttca     5160

agaactctgt agcaccgcct acatacctcg ctctgctaat cctgttacca gtggctgctg     5220

ccagtggcga taagtcgtgt cttaccgggt tggactcaag acgatagtta ccggataagg     5280

cgcagcggtc gggctgaacg gggggttcgt gcacacagcc cagcttggag cgaacgacct     5340

acaccgaact gagataccta cagcgtgagc tatgagaaag cgccacgctt cccgaaggga     5400

gaaaggcgga caggtatccg gtaagcggca gggtcggaac aggagagcgc acgagggagc     5460

ttccaggggg aaacgcctgg tatctttata gtcctgtcgg gtttcgccac ctctgacttg     5520

agcgtcgatt tttgtgatgc tcgtcagggg ggcggagcct atggaaaaac gccagcaacg     5580

cggccttttt acggttcctg gccttttgct ggccttttgc tcacatgttc tttcctgcgt     5640

tatcccctga ttctgtggat aaccgtatta ccgcctttga gtgagctgat accgctcgcc     5700

gcagccgaac gaccgagcgc agcgagtcag tgagcgagga agcggaagag cgcccaatac     5760

gcaaaccgcc tctccccgcg cgttggccga ttcattaatg cagctggcac gacaggtttc     5820

ccgactggaa agcgggcagt gagcgcaacg caattaatgt gagttagctc actcattagg     5880

caccccaggc tttacacttt atgcttccgg ctcgtatgtt gtgtggaatt gtgagcggat     5940

aacaatttca cacaggaaac agctatgacc atgattacgc cagatttaat taaggcctta     6000

attag                                                                 6005


<210>  8
<211>  6044
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  AAV with human MMACHC HA

<400>  8
gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc gggcgacctt       60

tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca actccatcac      120

taggggttcc ttgtagttaa tgattaaccc gccatgctac ttatctacca gggtaatggg      180

gatcctctag aactatagct agtcgacatt gattattgac tagttattaa tagtaatcaa      240

ttacggggtc attagttcat agcccatata tggagttccg cgttacataa cttacggtaa      300

atggcccgcc tggctgaccg cccaacgacc cccgcccatt gacgtcaata atgacgtatg      360

ttcccatagt aacgccaata gggactttcc attgacgtca atgggtggag tatttacggt      420

aaactgccca cttggcagta catcaagtgt atcatatgcc aagtacgccc cctattgacg      480

tcaatgacgg taaatggccc gcctggcatt atgcccagta catgacctta tgggactttc      540

ctacttggca gtacatctac gtattagtca tcgctattac catggtcgag gtgagcccca      600

cgttctgctt cactctcccc atctcccccc cctccccacc cccaattttg tatttattta      660

ttttttaatt attttgtgca gcgatggggg cggggggggg gggggggcgc gcgccaggcg      720

gggcggggcg gggcgagggg cggggcgggg cgaggcggag aggtgcggcg gcagccaatc      780

agagcggcgc gctccgaaag tttcctttta tggcgaggcg gcggcggcgg cggccctata      840

aaaagcgaag cgcgcggcgg gcgggagtcg ctgcgcgctg ccttcgcccc gtgccccgct      900

ccgccgccgc ctcgcgccgc ccgccccggc tctgactgac cgcgttactc ccacaggtga      960

gcgggcggga cggcccttct cctccgggct gtaattagcg cttggtttaa tgacggcttg     1020

tttcttttct gtggctgcgt gaaagccttg aggggctccg ggagggccct ttgtgcgggg     1080

ggagcggctc ggggggtgcg tgcgtgtgtg tgtgcgtggg gagcgccgcg tgcggctccg     1140

cgctgcccgg cggctgtgag cgctgcgggc gcggcgcggg gctttgtgcg ctccgcagtg     1200

tgcgcgaggg gagcgcggcc gggggcggtg ccccgcggtg cggggggggc tgcgagggga     1260

acaaaggctg cgtgcggggt gtgtgcgtgg gggggtgagc agggggtgtg ggcgcgtcgg     1320

tcgggctgca accccccctg cacccccctc cccgagttgc tgagcacggc ccggcttcgg     1380

gtgcggggct ccgtacgggg cgtggcgcgg ggctcgccgt gccgggcggg gggtggcggc     1440

aggtgggggt gccgggcggg gcggggccgc ctcgggccgg ggagggctcg ggggaggggc     1500

gcggcggccc ccggagcgcc ggcggctgtc gaggcgcggc gagccgcagc cattgccttt     1560

tatggtaatc gtgcgagagg gcgcagggac ttcctttgtc ccaaatctgt gcggagccga     1620

aatctgggag gcgccgccgc accccctcta gcgggcgcgg ggcgaagcgg tgcggcgccg     1680

gcaggaagga aatgggcggg gagggccttc gtgcgtcgcc gcgccgccgt ccccttctcc     1740

ctctccagcc tcggggctgt ccgcgggggg acggctgcct tcggggggga cggggcaggg     1800

cggggttcgg cttctggcgt gtgaccggcg gctctagagc ctctgctaac catgttcatg     1860

ccttcttctt tttcctacag ctcctgggca acgtgctggt tattgtgctg tctcatcatt     1920

ttggcaaaga attcgatatc gccgccacca tggaacctaa agtcgcagaa ctcaagcaga     1980

agatcgagga caccctgtgc ccgttcggat tcgaggtgta ccctttccaa gtggcctggt     2040

acaacgagct cctgccccct gctttccatt tgccactgcc cggtccgact ctcgcgtttc     2100

ttgtgctgtc gacccccgcg atgttcgacc gcgccctcaa gccgttcctg caatcatgtc     2160

atctgcggat gctgaccgat ccggtcgatc agtgcgtggc ctaccacctg ggtcgcgtca     2220

gggaatccct gccggagctt cagatcgaga tcatcgcgga ttacgaagtg cacccaaacc     2280

ggcggcccaa gattctcgcc caaaccgccg cgcacgtggc tggcgccgcc tattactacc     2340

agcgccagga cgtcgaggcg gacccttggg gcaatcagag aatctctgga gtgtgcatcc     2400

acccacggtt cgggggatgg ttcgcaattc ggggcgtggt gctgctgccg ggaatcgagg     2460

tgccagactt gcctcctcga aagccccacg actgcgtgcc aactagagcc gatagaattg     2520

ccctgctgga agggttcaac ttccattggc gcgactggac ctaccgggac gctgtgactc     2580

ctcaagaacg ctacagcgaa gaacagaagg cctacttttc aactccgccg gcccagcgcc     2640

tggcactcct gggactggcc cagccctccg agaagcctag ctccccctcg ccggacttgc     2700

ccttcaccac cccggccccc aaaaagcccg gcaaccctag ccgggccagg tcctggctgt     2760

ccccgagggt gtccccgcct gcctcccccg gccctggggg aagctcgtac ccgtatgatg     2820

tgcccgacta cgcctaatga aagcttctcg aggacggggt gaactacgcc tgaggatccg     2880

atctttttcc ctctgccaaa aattatgggg acatcatgaa gccccttgag catctgactt     2940

ctggctaata aaggaaattt attttcattg caatagtgtg ttggaatttt ttgtgtctct     3000

cactcggaag caattcgttg atctgaattt cgaccaccca taatacccat taccctggta     3060

gataagtagc atggcgggtt aatcattaac tacaaggaac ccctagtgat ggagttggcc     3120

actccctctc tgcgcgctcg ctcgctcact gaggccgggc gaccaaaggt cgcccgacgc     3180

ccgggctttg cccgggcggc ctcagtgagc gagcgagcgc gcagccttaa ttaacctaat     3240

tcactggccg tcgttttaca acgtcgtgac tgggaaaacc ctggcgttac ccaacttaat     3300

cgccttgcag cacatccccc tttcgccagc tggcgtaata gcgaagaggc ccgcaccgat     3360

cgcccttccc aacagttgcg cagcctgaat ggcgaatggg acgcgccctg tagcggcgca     3420

ttaagcgcgg cgggtgtggt ggttacgcgc agcgtgaccg ctacacttgc cagcgcccta     3480

gcgcccgctc ctttcgcttt cttcccttcc tttctcgcca cgttcgccgg ctttccccgt     3540

caagctctaa atcgggggct ccctttaggg ttccgattta gtgctttacg gcacctcgac     3600

cccaaaaaac ttgattaggg tgatggttca cgtagtgggc catcgccctg atagacggtt     3660

tttcgccctt tgacgttgga gtccacgttc tttaatagtg gactcttgtt ccaaactgga     3720

acaacactca accctatctc ggtctattct tttgatttat aagggatttt gccgatttcg     3780

gcctattggt taaaaaatga gctgatttaa caaaaattta acgcgaattt taacaaaata     3840

ttaacgctta caatttaggt ggcacttttc ggggaaatgt gcgcggaacc cctatttgtt     3900

tatttttcta aatacattca aatatgtatc cgctcatgag acaataaccc tgataaatgc     3960

ttcaataata ttgaaaaagg aagagtatga gtattcaaca tttccgtgtc gcccttattc     4020

ccttttttgc ggcattttgc cttcctgttt ttgctcaccc agaaacgctg gtgaaagtaa     4080

aagatgctga agatcagttg ggtgcacgag tgggttacat cgaactggat ctcaacagcg     4140

gtaagatcct tgagagtttt cgccccgaag aacgttttcc aatgatgagc acttttaaag     4200

ttctgctatg tggcgcggta ttatcccgta ttgacgccgg gcaagagcaa ctcggtcgcc     4260

gcatacacta ttctcagaat gacttggttg agtactcacc agtcacagaa aagcatctta     4320

cggatggcat gacagtaaga gaattatgca gtgctgccat aaccatgagt gataacactg     4380

cggccaactt acttctgaca acgatcggag gaccgaagga gctaaccgct tttttgcaca     4440

acatggggga tcatgtaact cgccttgatc gttgggaacc ggagctgaat gaagccatac     4500

caaacgacga gcgtgacacc acgatgcctg tagcaatggc aacaacgttg cgcaaactat     4560

taactggcga actacttact ctagcttccc ggcaacaatt aatagactgg atggaggcgg     4620

ataaagttgc aggaccactt ctgcgctcgg cccttccggc tggctggttt attgctgata     4680

aatctggagc cggtgagcgt gggtctcgcg gtatcattgc agcactgggg ccagatggta     4740

agccctcccg tatcgtagtt atctacacga cggggagtca ggcaactatg gatgaacgaa     4800

atagacagat cgctgagata ggtgcctcac tgattaagca ttggtaactg tcagaccaag     4860

tttactcata tatactttag attgatttaa aacttcattt ttaatttaaa aggatctagg     4920

tgaagatcct ttttgataat ctcatgacca aaatccctta acgtgagttt tcgttccact     4980

gagcgtcaga ccccgtagaa aagatcaaag gatcttcttg agatcctttt tttctgcgcg     5040

taatctgctg cttgcaaaca aaaaaaccac cgctaccagc ggtggtttgt ttgccggatc     5100

aagagctacc aactcttttt ccgaaggtaa ctggcttcag cagagcgcag ataccaaata     5160

ctgttcttct agtgtagccg tagttaggcc accacttcaa gaactctgta gcaccgccta     5220

catacctcgc tctgctaatc ctgttaccag tggctgctgc cagtggcgat aagtcgtgtc     5280

ttaccgggtt ggactcaaga cgatagttac cggataaggc gcagcggtcg ggctgaacgg     5340

ggggttcgtg cacacagccc agcttggagc gaacgaccta caccgaactg agatacctac     5400

agcgtgagct atgagaaagc gccacgcttc ccgaagggag aaaggcggac aggtatccgg     5460

taagcggcag ggtcggaaca ggagagcgca cgagggagct tccaggggga aacgcctggt     5520

atctttatag tcctgtcggg tttcgccacc tctgacttga gcgtcgattt ttgtgatgct     5580

cgtcaggggg gcggagccta tggaaaaacg ccagcaacgc ggccttttta cggttcctgg     5640

ccttttgctg gccttttgct cacatgttct ttcctgcgtt atcccctgat tctgtggata     5700

accgtattac cgcctttgag tgagctgata ccgctcgccg cagccgaacg accgagcgca     5760

gcgagtcagt gagcgaggaa gcggaagagc gcccaatacg caaaccgcct ctccccgcgc     5820

gttggccgat tcattaatgc agctggcacg acaggtttcc cgactggaaa gcgggcagtg     5880

agcgcaacgc aattaatgtg agttagctca ctcattaggc accccaggct ttacacttta     5940

tgcttccggc tcgtatgttg tgtggaattg tgagcggata acaatttcac acaggaaaca     6000

gctatgacca tgattacgcc agatttaatt aaggccttaa ttag                      6044


<210>  9
<211>  6098
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  AAV with human MMACHC 3xFLAG

<400>  9
gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc gggcgacctt       60

tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca actccatcac      120

taggggttcc ttgtagttaa tgattaaccc gccatgctac ttatctacca gggtaatggg      180

gatcctctag aactatagct agtcgacatt gattattgac tagttattaa tagtaatcaa      240

ttacggggtc attagttcat agcccatata tggagttccg cgttacataa cttacggtaa      300

atggcccgcc tggctgaccg cccaacgacc cccgcccatt gacgtcaata atgacgtatg      360

ttcccatagt aacgccaata gggactttcc attgacgtca atgggtggag tatttacggt      420

aaactgccca cttggcagta catcaagtgt atcatatgcc aagtacgccc cctattgacg      480

tcaatgacgg taaatggccc gcctggcatt atgcccagta catgacctta tgggactttc      540

ctacttggca gtacatctac gtattagtca tcgctattac catggtcgag gtgagcccca      600

cgttctgctt cactctcccc atctcccccc cctccccacc cccaattttg tatttattta      660

ttttttaatt attttgtgca gcgatggggg cggggggggg gggggggcgc gcgccaggcg      720

gggcggggcg gggcgagggg cggggcgggg cgaggcggag aggtgcggcg gcagccaatc      780

agagcggcgc gctccgaaag tttcctttta tggcgaggcg gcggcggcgg cggccctata      840

aaaagcgaag cgcgcggcgg gcgggagtcg ctgcgcgctg ccttcgcccc gtgccccgct      900

ccgccgccgc ctcgcgccgc ccgccccggc tctgactgac cgcgttactc ccacaggtga      960

gcgggcggga cggcccttct cctccgggct gtaattagcg cttggtttaa tgacggcttg     1020

tttcttttct gtggctgcgt gaaagccttg aggggctccg ggagggccct ttgtgcgggg     1080

ggagcggctc ggggggtgcg tgcgtgtgtg tgtgcgtggg gagcgccgcg tgcggctccg     1140

cgctgcccgg cggctgtgag cgctgcgggc gcggcgcggg gctttgtgcg ctccgcagtg     1200

tgcgcgaggg gagcgcggcc gggggcggtg ccccgcggtg cggggggggc tgcgagggga     1260

acaaaggctg cgtgcggggt gtgtgcgtgg gggggtgagc agggggtgtg ggcgcgtcgg     1320

tcgggctgca accccccctg cacccccctc cccgagttgc tgagcacggc ccggcttcgg     1380

gtgcggggct ccgtacgggg cgtggcgcgg ggctcgccgt gccgggcggg gggtggcggc     1440

aggtgggggt gccgggcggg gcggggccgc ctcgggccgg ggagggctcg ggggaggggc     1500

gcggcggccc ccggagcgcc ggcggctgtc gaggcgcggc gagccgcagc cattgccttt     1560

tatggtaatc gtgcgagagg gcgcagggac ttcctttgtc ccaaatctgt gcggagccga     1620

aatctgggag gcgccgccgc accccctcta gcgggcgcgg ggcgaagcgg tgcggcgccg     1680

gcaggaagga aatgggcggg gagggccttc gtgcgtcgcc gcgccgccgt ccccttctcc     1740

ctctccagcc tcggggctgt ccgcgggggg acggctgcct tcggggggga cggggcaggg     1800

cggggttcgg cttctggcgt gtgaccggcg gctctagagc ctctgctaac catgttcatg     1860

ccttcttctt tttcctacag ctcctgggca acgtgctggt tattgtgctg tctcatcatt     1920

ttggcaaaga attcgatatc gccgccacca tggaacctaa agtcgcagaa ctcaagcaga     1980

agatcgagga caccctgtgc ccgttcggat tcgaggtgta ccctttccaa gtggcctggt     2040

acaacgagct cctgccccct gctttccatt tgccactgcc cggtccgact ctcgcgtttc     2100

ttgtgctgtc gacccccgcg atgttcgacc gcgccctcaa gccgttcctg caatcatgtc     2160

atctgcggat gctgaccgat ccggtcgatc agtgcgtggc ctaccacctg ggtcgcgtca     2220

gggaatccct gccggagctt cagatcgaga tcatcgcgga ttacgaagtg cacccaaacc     2280

ggcggcccaa gattctcgcc caaaccgccg cgcacgtggc tggcgccgcc tattactacc     2340

agcgccagga cgtcgaggcg gacccttggg gcaatcagag aatctctgga gtgtgcatcc     2400

acccacggtt cgggggatgg ttcgcaattc ggggcgtggt gctgctgccg ggaatcgagg     2460

tgccagactt gcctcctcga aagccccacg actgcgtgcc aactagagcc gatagaattg     2520

ccctgctgga agggttcaac ttccattggc gcgactggac ctaccgggac gctgtgactc     2580

ctcaagaacg ctacagcgaa gaacagaagg cctacttttc aactccgccg gcccagcgcc     2640

tggcactcct gggactggcc cagccctccg agaagcctag ctccccctcg ccggacttgc     2700

ccttcaccac cccggccccc aaaaagcccg gcaaccctag ccgggccagg tcctggctgt     2760

ccccgagggt gtccccgcct gcctcccccg gccctggggg ttcctcggac tacaaagatg     2820

acgacgacaa gggagactat aaggacgacg acgataaggg agattacaag gatgacgatg     2880

acaagggcta atgaaagctt ctcgaggacg gggtgaacta cgcctgagga tccgatcttt     2940

ttccctctgc caaaaattat ggggacatca tgaagcccct tgagcatctg acttctggct     3000

aataaaggaa atttattttc attgcaatag tgtgttggaa ttttttgtgt ctctcactcg     3060

gaagcaattc gttgatctga atttcgacca cccataatac ccattaccct ggtagataag     3120

tagcatggcg ggttaatcat taactacaag gaacccctag tgatggagtt ggccactccc     3180

tctctgcgcg ctcgctcgct cactgaggcc gggcgaccaa aggtcgcccg acgcccgggc     3240

tttgcccggg cggcctcagt gagcgagcga gcgcgcagcc ttaattaacc taattcactg     3300

gccgtcgttt tacaacgtcg tgactgggaa aaccctggcg ttacccaact taatcgcctt     3360

gcagcacatc cccctttcgc cagctggcgt aatagcgaag aggcccgcac cgatcgccct     3420

tcccaacagt tgcgcagcct gaatggcgaa tgggacgcgc cctgtagcgg cgcattaagc     3480

gcggcgggtg tggtggttac gcgcagcgtg accgctacac ttgccagcgc cctagcgccc     3540

gctcctttcg ctttcttccc ttcctttctc gccacgttcg ccggctttcc ccgtcaagct     3600

ctaaatcggg ggctcccttt agggttccga tttagtgctt tacggcacct cgaccccaaa     3660

aaacttgatt agggtgatgg ttcacgtagt gggccatcgc cctgatagac ggtttttcgc     3720

cctttgacgt tggagtccac gttctttaat agtggactct tgttccaaac tggaacaaca     3780

ctcaacccta tctcggtcta ttcttttgat ttataaggga ttttgccgat ttcggcctat     3840

tggttaaaaa atgagctgat ttaacaaaaa tttaacgcga attttaacaa aatattaacg     3900

cttacaattt aggtggcact tttcggggaa atgtgcgcgg aacccctatt tgtttatttt     3960

tctaaataca ttcaaatatg tatccgctca tgagacaata accctgataa atgcttcaat     4020

aatattgaaa aaggaagagt atgagtattc aacatttccg tgtcgccctt attccctttt     4080

ttgcggcatt ttgccttcct gtttttgctc acccagaaac gctggtgaaa gtaaaagatg     4140

ctgaagatca gttgggtgca cgagtgggtt acatcgaact ggatctcaac agcggtaaga     4200

tccttgagag ttttcgcccc gaagaacgtt ttccaatgat gagcactttt aaagttctgc     4260

tatgtggcgc ggtattatcc cgtattgacg ccgggcaaga gcaactcggt cgccgcatac     4320

actattctca gaatgacttg gttgagtact caccagtcac agaaaagcat cttacggatg     4380

gcatgacagt aagagaatta tgcagtgctg ccataaccat gagtgataac actgcggcca     4440

acttacttct gacaacgatc ggaggaccga aggagctaac cgcttttttg cacaacatgg     4500

gggatcatgt aactcgcctt gatcgttggg aaccggagct gaatgaagcc ataccaaacg     4560

acgagcgtga caccacgatg cctgtagcaa tggcaacaac gttgcgcaaa ctattaactg     4620

gcgaactact tactctagct tcccggcaac aattaataga ctggatggag gcggataaag     4680

ttgcaggacc acttctgcgc tcggcccttc cggctggctg gtttattgct gataaatctg     4740

gagccggtga gcgtgggtct cgcggtatca ttgcagcact ggggccagat ggtaagccct     4800

cccgtatcgt agttatctac acgacgggga gtcaggcaac tatggatgaa cgaaatagac     4860

agatcgctga gataggtgcc tcactgatta agcattggta actgtcagac caagtttact     4920

catatatact ttagattgat ttaaaacttc atttttaatt taaaaggatc taggtgaaga     4980

tcctttttga taatctcatg accaaaatcc cttaacgtga gttttcgttc cactgagcgt     5040

cagaccccgt agaaaagatc aaaggatctt cttgagatcc tttttttctg cgcgtaatct     5100

gctgcttgca aacaaaaaaa ccaccgctac cagcggtggt ttgtttgccg gatcaagagc     5160

taccaactct ttttccgaag gtaactggct tcagcagagc gcagatacca aatactgttc     5220

ttctagtgta gccgtagtta ggccaccact tcaagaactc tgtagcaccg cctacatacc     5280

tcgctctgct aatcctgtta ccagtggctg ctgccagtgg cgataagtcg tgtcttaccg     5340

ggttggactc aagacgatag ttaccggata aggcgcagcg gtcgggctga acggggggtt     5400

cgtgcacaca gcccagcttg gagcgaacga cctacaccga actgagatac ctacagcgtg     5460

agctatgaga aagcgccacg cttcccgaag ggagaaaggc ggacaggtat ccggtaagcg     5520

gcagggtcgg aacaggagag cgcacgaggg agcttccagg gggaaacgcc tggtatcttt     5580

atagtcctgt cgggtttcgc cacctctgac ttgagcgtcg atttttgtga tgctcgtcag     5640

gggggcggag cctatggaaa aacgccagca acgcggcctt tttacggttc ctggcctttt     5700

gctggccttt tgctcacatg ttctttcctg cgttatcccc tgattctgtg gataaccgta     5760

ttaccgcctt tgagtgagct gataccgctc gccgcagccg aacgaccgag cgcagcgagt     5820

cagtgagcga ggaagcggaa gagcgcccaa tacgcaaacc gcctctcccc gcgcgttggc     5880

cgattcatta atgcagctgg cacgacaggt ttcccgactg gaaagcgggc agtgagcgca     5940

acgcaattaa tgtgagttag ctcactcatt aggcacccca ggctttacac tttatgcttc     6000

cggctcgtat gttgtgtgga attgtgagcg gataacaatt tcacacagga aacagctatg     6060

accatgatta cgccagattt aattaaggcc ttaattag                             6098


<210>  10
<211>  841
<212>  DNA
<213>  Mus musculus


<220>
<221>  misc_feature
<223>  wild-type mouse Mmachc

<400>  10
atggagccgc gagtcgcaga gctgaagcag aagattgagg acaccttgtg tccttttggc       60

ttcgaagttt atcccttcca ggtggcgtgg tacaatgaac tcctgcctcc agccttccac      120

ttgcccttcc caggacctac cctggccttc ctggtactca gcacacctgc tatgtttgac      180

agagccctca aacccttctt aaagagctgc cacttccaaa cactgagaga cccggtggat      240

caatgtgtgt cctaccacct gaggagtgtt acagagaagt ttccagaagt gcatatggaa      300

gtcattgctg actatgaggt acaccccaat cggcgaccta agattctcgc ccagacagca      360

gcccatgtgg caggtgctgc ttattactac caacgacaag atgtggatgc agacccatgg      420

gggacccagc acatagcagg tgtgtgcata cacccccgat ttgggggctg gtttgccatc      480

cgaggggtta tgttgctgcc agggattgaa gtgccaaatt tgccacccag aaagccccct      540

gactgtgtgc ctacaagagc tggccgcatc actctgcttg aaggtttcaa tttccattgg      600

cgggactgga cttaccgtga tgctgtgact cctgaagaac ggtactccga agaacagaag      660

atctactttt ccaccccacc tgcccaacgc ttggccctat taggcttagc ccaaccctca      720

gaacacccta gcactacatc tgagcttcct ctttccttgc ttactaaacc tcagaattcc      780

aggagagctc gaagctggct gagtccaagt gtctcaccac ctgtatcccc aggcccttga      840

t                                                                      841


<210>  11
<211>  885
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  human codon-optimized MMACHC with linker and HA

<400>  11
atggaaccta aagtcgcaga actcaagcag aagatcgagg acaccctgtg cccgttcgga       60

ttcgaggtgt accctttcca agtggcctgg tacaacgagc tcctgccccc tgctttccat      120

ttgccactgc ccggtccgac tctcgcgttt cttgtgctgt cgacccccgc gatgttcgac      180

cgcgccctca agccgttcct gcaatcatgt catctgcgga tgctgaccga tccggtcgat      240

cagtgcgtgg cctaccacct gggtcgcgtc agggaatccc tgccggagct tcagatcgag      300

atcatcgcgg attacgaagt gcacccaaac cggcggccca agattctcgc ccaaaccgcc      360

gcgcacgtgg ctggcgccgc ctattactac cagcgccagg acgtcgaggc ggacccttgg      420

ggcaatcaga gaatctctgg agtgtgcatc cacccacggt tcgggggatg gttcgcaatt      480

cggggcgtgg tgctgctgcc gggaatcgag gtgccagact tgcctcctcg aaagccccac      540

gactgcgtgc caactagagc cgatagaatt gccctgctgg aagggttcaa cttccattgg      600

cgcgactgga cctaccggga cgctgtgact cctcaagaac gctacagcga agaacagaag      660

gcctactttt caactccgcc ggcccagcgc ctggcactcc tgggactggc ccagccctcc      720

gagaagccta gctccccctc gccggacttg cccttcacca ccccggcccc caaaaagccc      780

ggcaacccta gccgggccag gtcctggctg tccccgaggg tgtccccgcc tgcctccccc      840

ggccctgggg gaagctcgta cccgtatgat gtgcccgact acgcc                      885


<210>  12
<211>  939
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  human codon-optimized MMACHC with linker and 3xFLAG

<400>  12
atggaaccta aagtcgcaga actcaagcag aagatcgagg acaccctgtg cccgttcgga       60

ttcgaggtgt accctttcca agtggcctgg tacaacgagc tcctgccccc tgctttccat      120

ttgccactgc ccggtccgac tctcgcgttt cttgtgctgt cgacccccgc gatgttcgac      180

cgcgccctca agccgttcct gcaatcatgt catctgcgga tgctgaccga tccggtcgat      240

cagtgcgtgg cctaccacct gggtcgcgtc agggaatccc tgccggagct tcagatcgag      300

atcatcgcgg attacgaagt gcacccaaac cggcggccca agattctcgc ccaaaccgcc      360

gcgcacgtgg ctggcgccgc ctattactac cagcgccagg acgtcgaggc ggacccttgg      420

ggcaatcaga gaatctctgg agtgtgcatc cacccacggt tcgggggatg gttcgcaatt      480

cggggcgtgg tgctgctgcc gggaatcgag gtgccagact tgcctcctcg aaagccccac      540

gactgcgtgc caactagagc cgatagaatt gccctgctgg aagggttcaa cttccattgg      600

cgcgactgga cctaccggga cgctgtgact cctcaagaac gctacagcga agaacagaag      660

gcctactttt caactccgcc ggcccagcgc ctggcactcc tgggactggc ccagccctcc      720

gagaagccta gctccccctc gccggacttg cccttcacca ccccggcccc caaaaagccc      780

ggcaacccta gccgggccag gtcctggctg tccccgaggg tgtccccgcc tgcctccccc      840

ggccctgggg gttcctcgga ctacaaagat gacgacgaca agggagacta taaggacgac      900

gacgataagg gagattacaa ggatgacgat gacaagggc                             939


