                         SEQUENCE LISTING

<110>  FUNDACION PARA LA INVESTIGACION MEDICA APLICADA
 
<120>  GENE THERAPY VECTOR EXPRESSING CYP27A1 FOR THE TREATMENT OF 
       CEREBROTENDIMOUS XANTHOMATOSIS

<130>  BEP200662

<150>  EP20190351
<151>  2020-08-10

<160>  21    

<170>  PatentIn version 3.5

<210>  1
<211>  531
<212>  PRT
<213>  homo sapiens

<400>  1

Met Ala Ala Leu Gly Cys Ala Arg Leu Arg Trp Ala Leu Arg Gly Ala 
1               5                   10                  15      


Gly Arg Gly Leu Cys Pro His Gly Ala Arg Ala Lys Ala Ala Ile Pro 
            20                  25                  30          


Ala Ala Leu Pro Ser Asp Lys Ala Thr Gly Ala Pro Gly Ala Gly Pro 
        35                  40                  45              


Gly Val Arg Arg Arg Gln Arg Ser Leu Glu Glu Ile Pro Arg Leu Gly 
    50                  55                  60                  


Gln Leu Arg Phe Phe Phe Gln Leu Phe Val Gln Gly Tyr Ala Leu Gln 
65                  70                  75                  80  


Leu His Gln Leu Gln Val Leu Tyr Lys Ala Lys Tyr Gly Pro Met Trp 
                85                  90                  95      


Met Ser Tyr Leu Gly Pro Gln Met His Val Asn Leu Ala Ser Ala Pro 
            100                 105                 110         


Leu Leu Glu Gln Val Met Arg Gln Glu Gly Lys Tyr Pro Val Arg Asn 
        115                 120                 125             


Asp Met Glu Leu Trp Lys Glu His Arg Asp Gln His Asp Leu Thr Tyr 
    130                 135                 140                 


Gly Pro Phe Thr Thr Glu Gly His His Trp Tyr Gln Leu Arg Gln Ala 
145                 150                 155                 160 


Leu Asn Gln Arg Leu Leu Lys Pro Ala Glu Ala Ala Leu Tyr Thr Asp 
                165                 170                 175     


Ala Phe Asn Glu Val Ile Asp Asp Phe Met Thr Arg Leu Asp Gln Leu 
            180                 185                 190         


Arg Ala Glu Ser Ala Ser Gly Asn Gln Val Ser Asp Met Ala Gln Leu 
        195                 200                 205             


Phe Tyr Tyr Phe Ala Leu Glu Ala Ile Cys Tyr Ile Leu Phe Glu Lys 
    210                 215                 220                 


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


Val Arg Ser Ile Gly Leu Met Phe Gln Asn Ser Leu Tyr Ala Thr Phe 
                245                 250                 255     


Leu Pro Lys Trp Thr Arg Pro Val Leu Pro Phe Trp Lys Arg Tyr Leu 
            260                 265                 270         


Asp Gly Trp Asn Ala Ile Phe Ser Phe Gly Lys Lys Leu Ile Asp Glu 
        275                 280                 285             


Lys Leu Glu Asp Met Glu Ala Gln Leu Gln Ala Ala Gly Pro Asp Gly 
    290                 295                 300                 


Ile Gln Val Ser Gly Tyr Leu His Phe Leu Leu Ala Ser Gly Gln Leu 
305                 310                 315                 320 


Ser Pro Arg Glu Ala Met Gly Ser Leu Pro Glu Leu Leu Met Ala Gly 
                325                 330                 335     


Val Asp Thr Thr Ser Asn Thr Leu Thr Trp Ala Leu Tyr His Leu Ser 
            340                 345                 350         


Lys Asp Pro Glu Ile Gln Glu Ala Leu His Glu Glu Val Val Gly Val 
        355                 360                 365             


Val Pro Ala Gly Gln Val Pro Gln His Lys Asp Phe Ala His Met Pro 
    370                 375                 380                 


Leu Leu Lys Ala Val Leu Lys Glu Thr Leu Arg Leu Tyr Pro Val Val 
385                 390                 395                 400 


Pro Thr Asn Ser Arg Ile Ile Glu Lys Glu Ile Glu Val Asp Gly Phe 
                405                 410                 415     


Leu Phe Pro Lys Asn Thr Gln Phe Val Phe Cys His Tyr Val Val Ser 
            420                 425                 430         


Arg Asp Pro Thr Ala Phe Ser Glu Pro Glu Ser Phe Gln Pro His Arg 
        435                 440                 445             


Trp Leu Arg Asn Ser Gln Pro Ala Thr Pro Arg Ile Gln His Pro Phe 
    450                 455                 460                 


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


Ile Ala Glu Leu Glu Met Gln Leu Leu Leu Ala Arg Leu Ile Gln Lys 
                485                 490                 495     


Tyr Lys Val Val Leu Ala Pro Glu Thr Gly Glu Leu Lys Ser Val Ala 
            500                 505                 510         


Arg Ile Val Leu Val Pro Asn Lys Lys Val Gly Leu Gln Phe Leu Gln 
        515                 520                 525             


Arg Gln Cys 
    530     


<210>  2
<211>  1596
<212>  DNA
<213>  artificial sequence

<220>
<223>  Nucleotide sequence encoding CYP27A1

<400>  2
atggctgcgc tgggctgcgc gaggctgagg tgggcgctgc gaggggccgg ccgtggcctc       60

tgcccccacg gggccagagc caaggccgcg atccctgccg ccctcccctc ggacaaggcc      120

accggagctc ccggagccgg gcctggtgtc cggcggcggc aacggagctt agaggagatt      180

ccacgtctag gacagctgcg cttcttcttt cagctgttcg ttcaaggcta tgccctgcaa      240

ctgcaccagt tacaggtgct ttacaaggcc aagtacggtc caatgtggat gtcctactta      300

gggcctcaga tgcacgtgaa cctggccagt gccccgctct tggagcaagt gatgcggcaa      360

gagggcaagt acccagtacg gaacgacatg gagctatgga aggagcaccg ggaccagcac      420

gacctgacct atgggccgtt caccacggaa ggacaccact ggtaccagct gcgccaggct      480

ctgaaccagc ggttgctgaa gccagcggaa gcagcgctct atacggatgc tttcaatgag      540

gtgattgatg actttatgac tcgactggac cagctgcggg cagagagtgc ttcggggaac      600

caggtgtcgg acatggctca actcttctac tactttgcct tggaagctat ttgctacatc      660

ctgttcgaga aacgcattgg ctgcctgcag cgatccatcc ccgaggacac cgtgaccttc      720

gtcagatcca tcgggttaat gttccagaac tcactctatg ccaccttcct ccccaagtgg      780

actcgccccg tgctgccttt ctggaagcga tacctggatg gttggaatgc catcttttcc      840

tttgggaaga agctgattga tgagaagctc gaagatatgg aggcccaact gcaggcagca      900

gggccagatg gcatccaggt gtctggctac ctgcacttct tactggccag tggacagctc      960

agtcctcggg aggccatggg cagcctgcct gagctgctca tggctggagt ggacacgaca     1020

tccaacacgc tgacatgggc cctgtaccac ctctcaaagg accctgagat ccaggaggcc     1080

ttgcacgagg aagtggtggg tgtggtgcca gccgggcaag tgccccagca caaggacttt     1140

gcccacatgc cgttgctcaa agctgtgctt aaggagactc tgcgtctcta ccctgtggtc     1200

cccacaaact cccggatcat agaaaaggaa attgaagttg atggcttcct cttccccaag     1260

aacacccagt ttgtgttctg ccactatgtg gtgtcccggg accccactgc cttctctgag     1320

cctgaaagct tccagcccca ccgctggctg agaaacagcc agcctgctac ccccaggatc     1380

cagcacccat ttggctctgt gccctttggc tatggggtcc gggcctgcct gggccgcagg     1440

attgcagagc tggagatgca gctactcctc gcaaggctga tccagaagta caaggtggtc     1500

ctggccccgg agacggggga gttgaagagt gtggcccgca ttgtcctggt tcccaataag     1560

aaagtgggcc tgcagttcct gcagagacag tgctga                               1596


<210>  3
<211>  2030
<212>  DNA
<213>  Artificial sequence

<220>
<223>  CYP27A1 regulatory element

<400>  3
ttaacttttg tgtcaaggca tttttgaaca agcaagggct atccctaaag tcatgaggca       60

gtattgtcct ggtgtaccat tgggtaatag tagtttcagg attagtctac ttgaaaggaa      120

ataagttctg agagtcgaag tgcaaaggaa tacaaaagaa agcattctta tgatctaaca      180

ctgtgaacta attggtgttt tctggtattt ggttaagtat agtataagga tttggcacta      240

taggatgtaa gagaattatg acctcgttaa tggctcctaa gtcttgaact agatcatata      300

tatatatata tatatataat tttttttttt tgagatggag tctcactctg ttgtccaggt      360

tggagtgcat ggcacaatct cagctcactg caatctccgc ctcccgggtt caagcgattc      420

tcctgcctca gtctccccaa gtagctggga tcacgtgtgc caccacgttt ttaaagcatg      480

gcctcctgtc cttcctgtcc aaaaaccaaa tgaaaaatat ggtctaggtt gggtgctgtg      540

gctcacacct gtaattccag cactttggga ggccgaggta ggtagatcat ctgaggtcag      600

gagtttgaga ccagcctggc caacatggca aaaccctatc tctactaaaa atacaaaaat      660

tagccgggcg tggtggcggg cacctctaat tccagctact ctggaggctg agaccggaga      720

attgcttgaa ccgggaggcg gaggttgcag cgagccagga ttgcaccact gcactccagc      780

ctggacgaca gggtgagact ctggggagtg gggaggagag aattaacaaa ctatatgaca      840

caaaggaaca aaaatacaca agacaggata agagagagga aggatacagg gagagctaac      900

atacatatag cagtttgaag tcccgggaaa ggagaaaaaa atggggagga gcaatatttg      960

aacagataat atctgagaaa ctccccagac tgatcaaaga catccagtca cagagtcaag     1020

aaactaggag tcctagaata aataagtaga aagccacacc tagcaactca gctgtcagcc     1080

taattgaact taatatgccc tttcttctct ggctgcctgt aaatcaccaa tttttcaaat     1140

gctgttagaa ccagctgtac catcctgctg ggtccttcat tcctggcttg aatgtgatct     1200

ttgaccctgt atttatttta tacttgcgtg agttatgttt ttaaactttt tgacaactat     1260

actttgaata tacatgaaac ataggattca taagacaata cttttttttt cttcttgctg     1320

tacgttttcc gtactatgtt actctttcca ttttattaaa aataattctg gccatcatct     1380

acgaaatctg gtctcaacct gcagtttgaa atatcctgcc ttggcagacg cggcagggag     1440

gtgcgtggag ggagaattga attaaaaaaa aaaacaacaa aacacgaata tttagatttc     1500

tttgttcagc ggcccccctc cagggatcag atgactggcc cccctcgctc cgaactgact     1560

ccgggatcaa tccggaaggc cattgggaga agccgagggc agcttagcca cggccggttc     1620

ccgttccctc caggacgcga gggtcgcctt gggtggggaa ccgcgaccgg gcgaggacct     1680

atcccggtgt ggggcttccc gatttcgaaa gaatctcgct gcacccccgc ccagagttca     1740

gaccaagcga aaagttattt gagaggcctc gggggcgcgg ggtgaggagt cgtggcggag     1800

gccttggtcg gggcgccgtg gatatccccg agtcaccgcg tccctctcct gcagctcccg     1860

cgtcgctggg aggagcgagg gagcgagcgg gaaggggtct agctggcctt tgctcggccc     1920

tccccagcgc ccggctttga acccgccctg cactgctgtc tgggcgggtc cggggactca     1980

gcactcgacc caaaggtgca ggcgcgcgag cacaacccgc tagcgaattc                2030


<210>  4
<211>  305
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Human alpha-1 anti-trypsin gene promoter

<400>  4
cgccaccccc tccaccttgg acacaggacg ctgtggtttc tgagccaggt acaatgactc       60

ctttcggtaa gtgcagtgga agctgtacac tgcccaggca aagcgtccgg gcagcgtagg      120

cgggcgactc agatcccagc cagtggactt agcccctgtt tgctcctccg ataactgggg      180

tgaccttggt taatattcac cagcagcctc ccccgttgcc cctctggatc cactgcttaa      240

atacggacga ggacagggcc ctgtctcctc agcttcaggc accaccactg acctgggaca      300

gtgaa                                                                  305


<210>  5
<211>  384
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Mouse serum albumin enhancer

<400>  5
gttcctagat tacactacac attctgcaag catagcacag agcaatgttc tactttaatt       60

actttcattt tcttgtatcc tcacagccta gaaaataacc tgcgttacag catccactca      120

gtatcccttg agcatgaggt gacactactt aacataggga cgagatggta ctttgtgtct      180

cctgctctgt cagcagggca cagtacttgc tgataccagg gaatgtttgt tcttaaatac      240

catcattccg gacgtgtttg ccttggccag ttttccatgt acatgcagaa agaagtttgg      300

actgatcaat acagtcctct gcctttaaag caataggaaa aggccaactt gtctacgttt      360

agtatgtggc tgtagatctg tacc                                             384


<210>  6
<211>  689
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Chimeric promoter sequence EATT

<400>  6
gttcctagat tacactacac attctgcaag catagcacag agcaatgttc tactttaatt       60

actttcattt tcttgtatcc tcacagccta gaaaataacc tgcgttacag catccactca      120

gtatcccttg agcatgaggt gacactactt aacataggga cgagatggta ctttgtgtct      180

cctgctctgt cagcagggca cagtacttgc tgataccagg gaatgtttgt tcttaaatac      240

catcattccg gacgtgtttg ccttggccag ttttccatgt acatgcagaa agaagtttgg      300

actgatcaat acagtcctct gcctttaaag caataggaaa aggccaactt gtctacgttt      360

agtatgtggc tgtagatctg tacccgccac cccctccacc ttggacacag gacgctgtgg      420

tttctgagcc aggtacaatg actcctttcg gtaagtgcag tggaagctgt acactgccca      480

ggcaaagcgt ccgggcagcg taggcgggcg actcagatcc cagccagtgg acttagcccc      540

tgtttgctcc tccgataact ggggtgacct tggttaatat tcaccagcag cctcccccgt      600

tgcccctctg gatccactgc ttaaatacgg acgaggacag ggccctgtct cctcagcttc      660

aggcaccacc actgacctgg gacagtgaa                                        689


<210>  7
<211>  149
<212>  DNA
<213>  Artificial sequence

<220>
<223>  5'-ITR

<400>  7
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc       60

gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc tgcggccgc                                        149


<210>  8
<211>  148
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  3'-ITR

<400>  8
gcggccgcag gaacccctag tgatggagtt ggccactccc tctctgcgcg ctcgctcgct       60

cactgaggcc gggcgaccaa aggtcgcccg acgcccgggc tttgcccggg cggcctcagt      120

gagcgagcga gcgcgcagct gcctgcag                                         148


<210>  9
<211>  2945
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Nucleic acid construct: ITR-EAAT-CYP27A1-polyA-ITR

<400>  9
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc       60

gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca      120

actccatcac taggggttcc tgcggccgca cgcgtgttcc tagattacac tacacattct      180

gcaagcatag cacagagcaa tgttctactt taattacttt cattttcttg tatcctcaca      240

gcctagaaaa taacctgcgt tacagcatcc actcagtatc ccttgagcat gaggtgacac      300

tacttaacat agggacgaga tggtactttg tgtctcctgc tctgtcagca gggcacagta      360

cttgctgata ccagggaatg tttgttctta aataccatca ttccggacgt gtttgccttg      420

gccagttttc catgtacatg cagaaagaag tttggactga tcaatacagt cctctgcctt      480

taaagcaata ggaaaaggcc aacttgtcta cgtttagtat gtggctgtag atctgtaccc      540

gccaccccct ccaccttgga cacaggacgc tgtggtttct gagccaggta caatgactcc      600

tttcggtaag tgcagtggaa gctgtacact gcccaggcaa agcgtccggg cagcgtaggc      660

gggcgactca gatcccagcc agtggactta gcccctgttt gctcctccga taactggggt      720

gaccttggtt aatattcacc agcagcctcc cccgttgccc ctctggatcc actgcttaaa      780

tacggacgag gacagggccc tgtctcctca gcttcaggca ccaccactga cctgggacag      840

tgaagcggcc gctagcgaat tcttggcatt ccggtactgt tggtaaagcc accatggctg      900

cgctgggctg cgcgaggctg aggtgggcgc tgcgaggggc cggccgtggc ctctgccccc      960

acggggccag agccaaggcc gcgatccctg ccgccctccc ctcggacaag gccaccggag     1020

ctcccggagc cgggcctggt gtccggcggc ggcaacggag cttagaggag attccacgtc     1080

taggacagct gcgcttcttc tttcagctgt tcgttcaagg ctatgccctg caactgcacc     1140

agttacaggt gctttacaag gccaagtacg gtccaatgtg gatgtcctac ttagggcctc     1200

agatgcacgt gaacctggcc agtgccccgc tcttggagca agtgatgcgg caagagggca     1260

agtacccagt acggaacgac atggagctat ggaaggagca ccgggaccag cacgacctga     1320

cctatgggcc gttcaccacg gaaggacacc actggtacca gctgcgccag gctctgaacc     1380

agcggttgct gaagccagcg gaagcagcgc tctatacgga tgctttcaat gaggtgattg     1440

atgactttat gactcgactg gaccagctgc gggcagagag tgcttcgggg aaccaggtgt     1500

cggacatggc tcaactcttc tactactttg ccttggaagc tatttgctac atcctgttcg     1560

agaaacgcat tggctgcctg cagcgatcca tccccgagga caccgtgacc ttcgtcagat     1620

ccatcgggtt aatgttccag aactcactct atgccacctt cctccccaag tggactcgcc     1680

ccgtgctgcc tttctggaag cgatacctgg atggttggaa tgccatcttt tcctttggga     1740

agaagctgat tgatgagaag ctcgaagata tggaggccca actgcaggca gcagggccag     1800

atggcatcca ggtgtctggc tacctgcact tcttactggc cagtggacag ctcagtcctc     1860

gggaggccat gggcagcctg cctgagctgc tcatggctgg agtggacacg acatccaaca     1920

cgctgacatg ggccctgtac cacctctcaa aggaccctga gatccaggag gccttgcacg     1980

aggaagtggt gggtgtggtg ccagccgggc aagtgcccca gcacaaggac tttgcccaca     2040

tgccgttgct caaagctgtg cttaaggaga ctctgcgtct ctaccctgtg gtccccacaa     2100

actcccggat catagaaaag gaaattgaag ttgatggctt cctcttcccc aagaacaccc     2160

agtttgtgtt ctgccactat gtggtgtccc gggaccccac tgccttctct gagcctgaaa     2220

gcttccagcc ccaccgctgg ctgagaaaca gccagcctgc tacccccagg atccagcacc     2280

catttggctc tgtgcccttt ggctatgggg tccgggcctg cctgggccgc aggattgcag     2340

agctggagat gcagctactc ctcgcaaggc tgatccagaa gtacaaggtg gtcctggccc     2400

cggagacggg ggagttgaag agtgtggccc gcattgtcct ggttcccaat aagaaagtgg     2460

gcctgcagtt cctgcagaga cagtgctgag cggccaacaa tgcgatccga tggccgcgac     2520

tctagagtcg gggcggccgg ccgcttcgag cagacatgat aagatacatt gatgagtttg     2580

gacaaaccac aactagaatg cagtgaaaaa aatgctttat ttgtgaaatt tgtgatgcta     2640

ttgctttatt tgtaaccatt ataagctgca ataaacaagt taacaacaac aattgcattc     2700

attttatgtt tcaggttcag ggggaggtgt gggaggtttt ttaaagcaag taaaacctct     2760

acaaatgtgg taaaatcgat aagcccgtgc ggaccgagcg gccgcaggaa cccctagtga     2820

tggagttggc cactccctct ctgcgcgctc gctcgctcac tgaggccggg cgaccaaagg     2880

tcgcccgacg cccgggcttt gcccgggcgg cctcagtgag cgagcgagcg cgcagctgcc     2940

tgcag                                                                 2945


<210>  10
<211>  21
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Human Cyp27A1 Forward primer

<400>  10
tgtgcttaag gagactctgc g                                                 21


<210>  11
<211>  22
<212>  DNA
<213>  Artificial sequence

<220>
<223>  Human Cyp27a1 Reverse primer

<400>  11
atagtggcag aacacaaact gg                                                22


<210>  12
<211>  22
<212>  DNA
<213>  artificial sequence

<220>
<223>  Mouse Cyp27a1 exons 1/2 Forward primer

<400>  12
acaaggctat gtgctgcact tg                                                22


<210>  13
<211>  22
<212>  DNA
<213>  artificial sequence

<220>
<223>  Mouse Cyp27a1 exons 1/2 reverse primer

<400>  13
tgatccatgt ggtctcttat tg                                                22


<210>  14
<211>  20
<212>  DNA
<213>  artificial sequence

<220>
<223>  Mouse Cyp27a1 exons 8/9 forward primer

<400>  14
atggctgagg aagaaagagg                                                   20


<210>  15
<211>  23
<212>  DNA
<213>  artificial sequence

<220>
<223>  Mouse Cyp27a1 exons 8/9 reverse primer

<400>  15
acacagtctt tacttctccc atc                                               23


<210>  16
<211>  20
<212>  DNA
<213>  artificial sequence

<220>
<223>  Mouse Cyp7a1 forward primer

<400>  16
gaagcaatga aagcagcctc                                                   20


<210>  17
<211>  20
<212>  DNA
<213>  artificial sequence

<220>
<223>  Mouse Cyp7a1 reverse primer

<400>  17
gtaaatggca ttccctccag                                                   20


<210>  18
<211>  27
<212>  DNA
<213>  artificial sequence

<220>
<223>  Mouse Cyp3a11 forward primer

<400>  18
tgaatatgaa acttgctctc actaaaa                                           27


<210>  19
<211>  24
<212>  DNA
<213>  artificial sequence

<220>
<223>  Mouse Cyp3a11reverse primer

<400>  19
ccttgtctgc ttaatttcag aggt                                              24


<210>  20
<211>  21
<212>  DNA
<213>  artificial sequence

<220>
<223>  Mouse 36b4 forward primer

<400>  20
aacaatctcc cccttctcct t                                                 21


<210>  21
<211>  20
<212>  DNA
<213>  artificial sequence

<220>
<223>  Mouse 36b4 reverse primer

<400>  21
gaaggccttg accttttcag                                                   20


