                         SEQUENCE LISTING

<110>  Consejo Superior de Investigaciones Científicas (CSIC)
 
<120>  DOUBLE AND INDUCIBLE SUICIDE GENE CONSTRUCT AND ITS USE 
IN GENE THERAPY
        
<130>  PCT1641.1285

<150>  EP18382792
<151>  2018-11-07

<160>  12    

<170>  PatentIn version 3.5

<210>  1
<211>  1200
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Encoding nucleotide sequence for the icaspase9 protein

<400>  1
atgctcgagg gagtgcaggt ggaaaccatc tccccaggag acgggcgcac cttccccaag       60

cgcggccaga cctgcgtggt gcactacacc gggatgcttg aagatggaaa gaaagttgat      120

tcctcccggg acagaaacaa gccctttaag tttatgctag gcaagcagga ggtgatccga      180

ggctgggaag aaggggttgc ccagatgagt gtgggtcaga gagccaaact gactatatct      240

ccagattatg cctatggtgc cactgggcac ccaggcatca tcccaccaca tgccactctc      300

gtcttcgatg tggagcttct aaaactggaa tctggcggtg gatccggagt cgacggattt      360

ggtgatgtcg gtgctcttga gagtttgagg ggaaatgcag atttggctta catcctgagc      420

atggagccct gtggccactg cctcattatc aacaatgtga acttctgccg tgagtccggg      480

ctccgcaccc gcactggctc caacatcgac tgtgagaagt tgcggcgtcg cttctcctcg      540

ctgcatttca tggtggaggt gaagggcgac ctgactgcca agaaaatggt gctggctttg      600

ctggagctgg cgcagcagga ccacggtgct ctggactgct gcgtggtggt cattctctct      660

cacggctgtc aggccagcca cctgcagttc ccaggggctg tctacggcac agatggatgc      720

cctgtgtcgg tcgagaagat tgtgaacatc ttcaatggga ccagctgccc cagcctggga      780

gggaagccca agctcttttt catccaggcc tgtggtgggg agcagaaaga ccatgggttt      840

gaggtggcct ccacttcccc tgaagacgag tcccctggca gtaaccccga gccagatgcc      900

accccgttcc aggaaggttt gaggaccttc gaccagctgg acgccatatc tagtttgccc      960

acacccagtg acatctttgt gtcctactct actttcccag gttttgtttc ctggagggac     1020

cccaagagtg gctcctggta cgttgagacc ctggacgaca tctttgagca gtgggctcac     1080

tctgaagacc tgcagtccct cctgcttagg gtcgctaatg ctgtttcggt gaaagggatt     1140

tataaacaga tgcctggttg ctttaatttc ctccggaaaa aacttttctt taaaacatca     1200


<210>  2
<211>  1128
<212>  DNA
<213>  Herpes simplex

<400>  2
atggcttcgt acccctgcca tcaacacgcg tctgcgttcg accaggctgc gcgttctcgc       60

ggccataaca accgacgtac ggcgttgcgc cctcgccggc aacaaaaagc cacggaagtc      120

cgcctggagc agaaaatgcc cacgctactg cgggtttata tagacggtcc ccacgggatg      180

gggaaaacca ccaccacgca actgctggtg gccctgggtt cgcgcgacga tatcgtctac      240

gtacccgagc cgatgactta ctggcgggtg ttgggggctt ccgagacaat cgcgaacatc      300

tacaccacac aacaccgcct cgaccagggt gagatatcgg ccggggacgc ggcggtggta      360

atgacaagcg cccagataac aatgggcatg ccttatgccg tgaccgacgc cgttctggct      420

cctcatatcg ggggggaggc tgggagctca catgccccgc ccccggccct caccctcatc      480

ttcgaccgcc atcccatcgc cgccctcctg tgctacccgg ccgcgcgata ccttatgggc      540

agcatgaccc cccaggccgt gctggcgttc gtggccctca tcccgccgac cttgcccggc      600

acaaacatcg tgttgggggc ccttccggag gacagacaca tcgaccgcct ggccaaacgc      660

cagcgccccg gcgagcggct tgacctggct atgctggccg cgattcgccg cgtttatggg      720

ctgcttgcca atacggtgcg gtatctgcag ggcggcgggt cgtggcggga ggattgggga      780

cagctttcgg gggcggccgt gccgccccag ggtgccgagc cccagagcaa cgcgggccca      840

cgaccccata tcggggacac gttatttacc ctgtttcggg cccccgagtt gctggccccc      900

aacggcgacc tgtataacgt gtttgcctgg gctttggacg tcttggccaa acgcctccgt      960

cccatgcatg tctttatcct ggattacgac caatcgcccg ccggctgccg ggacgccctg     1020

ctgcaactta cctccgggat ggtccagacc cacgtcacca ccccaggctc cataccgacg     1080

atctgcgacc tggcgcgcac gtttgcccgg gagatggggg aggctaac                  1128


<210>  3
<211>  133
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Beta-globin intron

<400>  3
gtaagtatca aggttacaag acaggtttaa ggagaccaat agaaactggg cttgtcgaga       60

cagagaagac tcttgcgttt ctgataggca cctattggtc ttactgacat ccactttgcc      120

tttctctcca cag                                                         133


<210>  4
<211>  400
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of icaspase9

<400>  4

Met Leu Glu Gly Val Gln Val Glu Thr Ile Ser Pro Gly Asp Gly Arg 
1               5                   10                  15      


Thr Phe Pro Lys Arg Gly Gln Thr Cys Val Val His Tyr Thr Gly Met 
            20                  25                  30          


Leu Glu Asp Gly Lys Lys Val Asp Ser Ser Arg Asp Arg Asn Lys Pro 
        35                  40                  45              


Phe Lys Phe Met Leu Gly Lys Gln Glu Val Ile Arg Gly Trp Glu Glu 
    50                  55                  60                  


Gly Val Ala Gln Met Ser Val Gly Gln Arg Ala Lys Leu Thr Ile Ser 
65                  70                  75                  80  


Pro Asp Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Ile Pro Pro 
                85                  90                  95      


His Ala Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Ser Gly 
            100                 105                 110         


Gly Gly Ser Gly Val Asp Gly Phe Gly Asp Val Gly Ala Leu Glu Ser 
        115                 120                 125             


Leu Arg Gly Asn Ala Asp Leu Ala Tyr Ile Leu Ser Met Glu Pro Cys 
    130                 135                 140                 


Gly His Cys Leu Ile Ile Asn Asn Val Asn Phe Cys Arg Glu Ser Gly 
145                 150                 155                 160 


Leu Arg Thr Arg Thr Gly Ser Asn Ile Asp Cys Glu Lys Leu Arg Arg 
                165                 170                 175     


Arg Phe Ser Ser Leu His Phe Met Val Glu Val Lys Gly Asp Leu Thr 
            180                 185                 190         


Ala Lys Lys Met Val Leu Ala Leu Leu Glu Leu Ala Gln Gln Asp His 
        195                 200                 205             


Gly Ala Leu Asp Cys Cys Val Val Val Ile Leu Ser His Gly Cys Gln 
    210                 215                 220                 


Ala Ser His Leu Gln Phe Pro Gly Ala Val Tyr Gly Thr Asp Gly Cys 
225                 230                 235                 240 


Pro Val Ser Val Glu Lys Ile Val Asn Ile Phe Asn Gly Thr Ser Cys 
                245                 250                 255     


Pro Ser Leu Gly Gly Lys Pro Lys Leu Phe Phe Ile Gln Ala Cys Gly 
            260                 265                 270         


Gly Glu Gln Lys Asp His Gly Phe Glu Val Ala Ser Thr Ser Pro Glu 
        275                 280                 285             


Asp Glu Ser Pro Gly Ser Asn Pro Glu Pro Asp Ala Thr Pro Phe Gln 
    290                 295                 300                 


Glu Gly Leu Arg Thr Phe Asp Gln Leu Asp Ala Ile Ser Ser Leu Pro 
305                 310                 315                 320 


Thr Pro Ser Asp Ile Phe Val Ser Tyr Ser Thr Phe Pro Gly Phe Val 
                325                 330                 335     


Ser Trp Arg Asp Pro Lys Ser Gly Ser Trp Tyr Val Glu Thr Leu Asp 
            340                 345                 350         


Asp Ile Phe Glu Gln Trp Ala His Ser Glu Asp Leu Gln Ser Leu Leu 
        355                 360                 365             


Leu Arg Val Ala Asn Ala Val Ser Val Lys Gly Ile Tyr Lys Gln Met 
    370                 375                 380                 


Pro Gly Cys Phe Asn Phe Leu Arg Lys Lys Leu Phe Phe Lys Thr Ser 
385                 390                 395                 400 


<210>  5
<211>  376
<212>  PRT
<213>  Herpes simplex

<400>  5

Met Ala Ser Tyr Pro Cys His Gln His Ala Ser Ala Phe Asp Gln Ala 
1               5                   10                  15      


Ala Arg Ser Arg Gly His Asn Asn Arg Arg Thr Ala Leu Arg Pro Arg 
            20                  25                  30          


Arg Gln Gln Lys Ala Thr Glu Val Arg Leu Glu Gln Lys Met Pro Thr 
        35                  40                  45              


Leu Leu Arg Val Tyr Ile Asp Gly Pro His Gly Met Gly Lys Thr Thr 
    50                  55                  60                  


Thr Thr Gln Leu Leu Val Ala Leu Gly Ser Arg Asp Asp Ile Val Tyr 
65                  70                  75                  80  


Val Pro Glu Pro Met Thr Tyr Trp Arg Val Leu Gly Ala Ser Glu Thr 
                85                  90                  95      


Ile Ala Asn Ile Tyr Thr Thr Gln His Arg Leu Asp Gln Gly Glu Ile 
            100                 105                 110         


Ser Ala Gly Asp Ala Ala Val Val Met Thr Ser Ala Gln Ile Thr Met 
        115                 120                 125             


Gly Met Pro Tyr Ala Val Thr Asp Ala Val Leu Ala Pro His Ile Gly 
    130                 135                 140                 


Gly Glu Ala Gly Ser Ser His Ala Pro Pro Pro Ala Leu Thr Leu Ile 
145                 150                 155                 160 


Phe Asp Arg His Pro Ile Ala Ala Leu Leu Cys Tyr Pro Ala Ala Arg 
                165                 170                 175     


Tyr Leu Met Gly Ser Met Thr Pro Gln Ala Val Leu Ala Phe Val Ala 
            180                 185                 190         


Leu Ile Pro Pro Thr Leu Pro Gly Thr Asn Ile Val Leu Gly Ala Leu 
        195                 200                 205             


Pro Glu Asp Arg His Ile Asp Arg Leu Ala Lys Arg Gln Arg Pro Gly 
    210                 215                 220                 


Glu Arg Leu Asp Leu Ala Met Leu Ala Ala Ile Arg Arg Val Tyr Gly 
225                 230                 235                 240 


Leu Leu Ala Asn Thr Val Arg Tyr Leu Gln Gly Gly Gly Ser Trp Arg 
                245                 250                 255     


Glu Asp Trp Gly Gln Leu Ser Gly Ala Ala Val Pro Pro Gln Gly Ala 
            260                 265                 270         


Glu Pro Gln Ser Asn Ala Gly Pro Arg Pro His Ile Gly Asp Thr Leu 
        275                 280                 285             


Phe Thr Leu Phe Arg Ala Pro Glu Leu Leu Ala Pro Asn Gly Asp Leu 
    290                 295                 300                 


Tyr Asn Val Phe Ala Trp Ala Leu Asp Val Leu Ala Lys Arg Leu Arg 
305                 310                 315                 320 


Pro Met His Val Phe Ile Leu Asp Tyr Asp Gln Ser Pro Ala Gly Cys 
                325                 330                 335     


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


Thr Thr Pro Gly Ser Ile Pro Thr Ile Cys Asp Leu Ala Arg Thr Phe 
        355                 360                 365             


Ala Arg Glu Met Gly Glu Ala Asn 
    370                 375     


<210>  6
<211>  1388
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  EF1alpha Promoter

<400>  6
gacattgatt attgagtaca tttatattgg ctcatgtcca acattaccgc catgagtaat       60

tcatacaaaa ggactcgccc ctgccttggg gaatcccagg gaccgtcgtt aaactcccac      120

taacgtagaa cccagagatc gctgcgttcc cgccccctca cccgcccgct ctcgtcatca      180

ctgaggtgga gaagagcatg cgtgaggctc cggtgcccgt cagtgggcag agcgcacatc      240

gcccacagtc cccgagaagt tggggggagg ggtcggcaat tgaaccggtg cctagagaag      300

gtggcgcggg gtaaactggg aaagtgatgt cgtgtactgg ctccgccttt ttcccgaggg      360

tgggggagaa ccgtatataa gtgcagtagt cgccgtgaac gttctttttc gcaacgggtt      420

tgccgccaga acacaggtaa gtgccgtgtg tggttcccgc gggcctggcc tctttacggg      480

ttatggccct tgcgtgcctt gaattacttc cacgcccctg gctgcagtac gtgattcttg      540

atcccgagct tcgggttgga agtgggtggg agagttcgag gccttgcgct taaggagccc      600

cttcgcctcg tgcttgagtt gaggcctggc ttgggcgctg gggccgccgc gtgcgaatct      660

ggtggcacct tcgcgcctgt ctcgctgctt tcgataagtc tctagccatt taaaattttt      720

gatgacctgc tgcgacgctt tttttctggc aagatagtct tgtaaatgcg ggccaagatc      780

tgcacactgg tatttcggtt tttggggccg cgggcggcga cggggcccgt gcgtcccagc      840

gcacatgttc ggcgaggcgg ggcctgcgag cgcggccacc gagaatcgga cgggggtagt      900

ctcaagctgg ccggcctgct ctggtgcctg gcctcgcgcc gccgtgtatc gccccgccct      960

gggcggcaag gctggcccgg tcggcaccag ttgcgtgagc ggaaagatgg ccgcttcccg     1020

gccctgctgc agggagctca aaatggagga cgcggcgctc gggagagcgg gcgggtgagt     1080

cacccacaca aaggaaaagg gcctttccgt cctcagccgt cgcttcatgt gactccacgg     1140

agtaccgggc gccgtccagg cacctcgatt agttctcgag cttttggagt acgtcgtctt     1200

taggttgggg ggaggggttt tatgcgatgg agtttcccca cactgagtgg gtggagactg     1260

aagttaggcc agcttggcac ttgatgtaat tctccttgga atttgccctt tttgagtttg     1320

gatcttggtt cattctcaag cctcagacag tggttcaaag tttttttctt ccatttcagg     1380

tgtcgtga                                                              1388


<210>  7
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  T2A Element

<400>  7

Ala Ser Arg Ala Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val 
1               5                   10                  15      


Glu Glu Asn Pro Gly Pro 
            20          


<210>  8
<211>  66
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Encoding nucleotide sequence for the T2A element

<400>  8
gctagcagag ccgagggcag gggaagtctt ctaacatgcg gggacgtgga ggaaaatccc       60

gggccc                                                                  66


<210>  9
<211>  22
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  P2A Element

<400>  9

Gly Ser Gly Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val 
1               5                   10                  15      


Glu Glu Asn Pro Gly Pro 
            20          


<210>  10
<211>  66
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Encoding nucleotide sequence for the P2A element

<400>  10
ggaagcggag ctactaactt cagcctgctg aagcaggctg gagacgtgga ggagaaccct       60

ggacct                                                                  66


<210>  11
<211>  840
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Encoding gene for the truncated membrane receptor dNGFR 

<400>  11
atgggggcag gtgccaccgg ccgcgccatg gacgggccgc gcctgctgct gttgctgctt       60

ctgggggtgt cccttggagg tgccaaggag gcatgcccca caggcctgta cacacacagc      120

ggtgagtgct gcaaagcctg caacctgggc gagggtgtgg cccagccttg tggagccaac      180

cagaccgtgt gtgagccctg cctggacagc gtgacgttct ccgacgtggt gagcgcgacc      240

gagccgtgca agccgtgcac cgagtgcgtg gggctccaga gcatgtcggc gccgtgcgtg      300

gaggccgacg acgccgtgtg ccgctgcgcc tacggctact accaggatga gacgactggg      360

cgctgcgagg cgtgccgcgt gtgcgaggcg ggctcgggcc tcgtgttctc ctgccaggac      420

aagcagaaca ccgtgtgcga ggagtgcccc gacggcacgt attccgacga ggccaaccac      480

gtggacccgt gcctgccctg caccgtgtgc gaggacaccg agcgccagct ccgcgagtgc      540

acacgctggg ccgacgccga gtgcgaggag atccctggcc gttggattac acggtccaca      600

cccccagagg gctcggacag cacagccccc agcacccagg agcctgaggc acctccagaa      660

caagacctca tagccagcac ggtggcaggt gtggtgacca cagtgatggg cagctcccag      720

cccgtggtga cccgaggcac caccgacaac ctcatccctg tctattgctc catcctggct      780

gctgtggttg tgggccttgt ggcctacata gccttcaaga ggtggaacag ggggattctc      840


<210>  12
<211>  280
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  dNGFR truncated membrane receptor 

<400>  12

Met Gly Ala Gly Ala Thr Gly Arg Ala Met Asp Gly Pro Arg Leu Leu 
1               5                   10                  15      


Leu Leu Leu Leu Leu Gly Val Ser Leu Gly Gly Ala Lys Glu Ala Cys 
            20                  25                  30          


Pro Thr Gly Leu Tyr Thr His Ser Gly Glu Cys Cys Lys Ala Cys Asn 
        35                  40                  45              


Leu Gly Glu Gly Val Ala Gln Pro Cys Gly Ala Asn Gln Thr Val Cys 
    50                  55                  60                  


Glu Pro Cys Leu Asp Ser Val Thr Phe Ser Asp Val Val Ser Ala Thr 
65                  70                  75                  80  


Glu Pro Cys Lys Pro Cys Thr Glu Cys Val Gly Leu Gln Ser Met Ser 
                85                  90                  95      


Ala Pro Cys Val Glu Ala Asp Asp Ala Val Cys Arg Cys Ala Tyr Gly 
            100                 105                 110         


Tyr Tyr Gln Asp Glu Thr Thr Gly Arg Cys Glu Ala Cys Arg Val Cys 
        115                 120                 125             


Glu Ala Gly Ser Gly Leu Val Phe Ser Cys Gln Asp Lys Gln Asn Thr 
    130                 135                 140                 


Val Cys Glu Glu Cys Pro Asp Gly Thr Tyr Ser Asp Glu Ala Asn His 
145                 150                 155                 160 


Val Asp Pro Cys Leu Pro Cys Thr Val Cys Glu Asp Thr Glu Arg Gln 
                165                 170                 175     


Leu Arg Glu Cys Thr Arg Trp Ala Asp Ala Glu Cys Glu Glu Ile Pro 
            180                 185                 190         


Gly Arg Trp Ile Thr Arg Ser Thr Pro Pro Glu Gly Ser Asp Ser Thr 
        195                 200                 205             


Ala Pro Ser Thr Gln Glu Pro Glu Ala Pro Pro Glu Gln Asp Leu Ile 
    210                 215                 220                 


Ala Ser Thr Val Ala Gly Val Val Thr Thr Val Met Gly Ser Ser Gln 
225                 230                 235                 240 


Pro Val Val Thr Arg Gly Thr Thr Asp Asn Leu Ile Pro Val Tyr Cys 
                245                 250                 255     


Ser Ile Leu Ala Ala Val Val Val Gly Leu Val Ala Tyr Ile Ala Phe 
            260                 265                 270         


Lys Arg Trp Asn Arg Gly Ile Leu 
        275                 280 


