                               SEQUENCE LISTING

<110> SHIRE HUMAN GENETIC THERAPIES, INC.
 
<120> CNS DELIVERY OF MRNA AND USES THEREOF

<130> 2006685-0689

<140>
<141>

<150> 62/020,161
<151> 2014-07-02

<150> 61/894,246
<151> 2013-10-22

<160> 15    

<170> PatentIn version 3.5

<210> 1
<211> 1511
<212> RNA
<213> Homo sapiens

<400> 1
ggggacccgc ggguuugcua uggcgaugag cagcggcggc agugguggcg gcgucccgga       60

gcaggaggau uccgugcugu uccggcgcgg cacaggccag agcgaugauu cugacauuug      120

ggaugauaca gcacugauaa aagcauauga uaaagcugug gcuucauuua agcaugcucu      180

aaagaauggu gacauuugug aaacuucggg uaaaccaaaa accacaccua aaagaaaacc      240

ugcuaagaag aauaaaagcc aaaagaagaa uacugcagcu uccuuacaac aguggaaagu      300

uggggacaaa uguucugcca uuuggucaga agacgguugc auuuacccag cuaccauugc      360

uucaauugau uuuaagagag aaaccugugu ugugguuuac acuggauaug gaaauagaga      420

ggagcaaaau cuguccgauc uacuuucccc aaucugugaa guagcuaaua auauagaaca      480

aaaugcucaa gagaaugaaa augaaagcca aguuucaaca gaugaaagug agaacuccag      540

gucuccugga aauaaaucag auaacaucaa gcccaaaucu gcuccaugga acucuuuucu      600

cccuccacca ccccccaugc cagggccaag acugggacca ggaaagccag gucuaaaauu      660

caauggccca ccaccgccac cgccaccacc accaccccac uuacuaucau gcuggcugcc      720

uccauuuccu ucuggaccac caauaauucc cccaccaccu cccauauguc cagauucucu      780

ugaugaugcu gaugcuuugg gaaguauguu aauuucaugg uacaugagug gcuaucauac      840

uggcuauuau auggguuuca gacaaaauca aaaagaagga aggugcucac auuccuuaaa      900

uuaaggagaa augcuggcau agagcagcac uaaaugacac cacuaaagaa acgaucagac      960

agaucuggaa ugugaagcgu uauagaagau aacuggccuc auuucuucaa aauaucaagu     1020

guugggaaag aaaaaaggaa guggaauggg uaacucuucu ugauuaaaag uuauguaaua     1080

accaaaugca augugaaaua uuuuacugga cucuauuuug aaaaaccauc uguaaaagac     1140

uggggugggg gugggaggcc agcacggugg ugaggcaguu gagaaaauuu gaauguggau     1200

uagauuuuga augauauugg auaauuauug guaauuuuua ugagcuguga gaaggguguu     1260

guaguuuaua aaagacuguc uuaauuugca uacuuaagca uuuaggaaug aaguguuaga     1320

gugucuuaaa auguuucaaa ugguuuaaca aaauguaugu gaggcguaug uggcaaaaug     1380

uuacagaauc uaacuggugg acauggcugu ucauuguacu guuuuuuucu aucuucuaua     1440

uguuuaaaag uauauaauaa aaauauuuaa uuuuuuuuua aaaaaaaaaa aaaaaaaaca     1500

aaaaaaaaaa a                                                          1511


<210> 2
<211> 294
<212> PRT
<213> Homo sapiens

<400> 2
Met Ala Met Ser Ser Gly Gly Ser Gly Gly Gly Val Pro Glu Gln Glu 
1               5                   10                  15      


Asp Ser Val Leu Phe Arg Arg Gly Thr Gly Gln Ser Asp Asp Ser Asp 
            20                  25                  30          


Ile Trp Asp Asp Thr Ala Leu Ile Lys Ala Tyr Asp Lys Ala Val Ala 
        35                  40                  45              


Ser Phe Lys His Ala Leu Lys Asn Gly Asp Ile Cys Glu Thr Ser Gly 
    50                  55                  60                  


Lys Pro Lys Thr Thr Pro Lys Arg Lys Pro Ala Lys Lys Asn Lys Ser 
65                  70                  75                  80  


Gln Lys Lys Asn Thr Ala Ala Ser Leu Gln Gln Trp Lys Val Gly Asp 
                85                  90                  95      


Lys Cys Ser Ala Ile Trp Ser Glu Asp Gly Cys Ile Tyr Pro Ala Thr 
            100                 105                 110         


Ile Ala Ser Ile Asp Phe Lys Arg Glu Thr Cys Val Val Val Tyr Thr 
        115                 120                 125             


Gly Tyr Gly Asn Arg Glu Glu Gln Asn Leu Ser Asp Leu Leu Ser Pro 
    130                 135                 140                 


Ile Cys Glu Val Ala Asn Asn Ile Glu Gln Asn Ala Gln Glu Asn Glu 
145                 150                 155                 160 


Asn Glu Ser Gln Val Ser Thr Asp Glu Ser Glu Asn Ser Arg Ser Pro 
                165                 170                 175     


Gly Asn Lys Ser Asp Asn Ile Lys Pro Lys Ser Ala Pro Trp Asn Ser 
            180                 185                 190         


Phe Leu Pro Pro Pro Pro Pro Met Pro Gly Pro Arg Leu Gly Pro Gly 
        195                 200                 205             


Lys Pro Gly Leu Lys Phe Asn Gly Pro Pro Pro Pro Pro Pro Pro Pro 
    210                 215                 220                 


Pro Pro His Leu Leu Ser Cys Trp Leu Pro Pro Phe Pro Ser Gly Pro 
225                 230                 235                 240 


Pro Ile Ile Pro Pro Pro Pro Pro Ile Cys Pro Asp Ser Leu Asp Asp 
                245                 250                 255     


Ala Asp Ala Leu Gly Ser Met Leu Ile Ser Trp Tyr Met Ser Gly Tyr 
            260                 265                 270         


His Thr Gly Tyr Tyr Met Gly Phe Arg Gln Asn Gln Lys Glu Gly Arg 
        275                 280                 285             


Cys Ser His Ser Leu Asn 
    290                 


<210> 3
<211> 885
<212> RNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polynucleotide

<400> 3
auggccauga gcagcggagg cagcggcgga ggagugcccg agcaggagga cagcgugcug       60

uucaggagag gcaccggcca gagcgaugac agcgauaucu gggacgauac cgcucugauc      120

aaggccuacg acaaggccgu ggccagcuuc aagcacgccc ugaaaaacgg cgacaucugc      180

gagaccagcg gcaagcccaa gacaaccccc aagagaaagc ccgccaagaa gaauaagagc      240

cagaaaaaga acaccgccgc cagccugcag caguggaagg ugggcgacaa gugcagcgcc      300

aucuggagcg aggacggcug caucuacccc gccaccaucg ccagcaucga cuucaagaga      360

gagaccugcg uggucgugua caccggcuac ggcaacagag aggagcagaa ccugagcgac      420

cugcugagcc ccauuuguga gguggccaau aacaucgaac agaacgccca ggagaacgag      480

aaugaaagcc aggugagcac cgacgagagc gagaacagca gaucuccugg caacaagagc      540

gacaacauca agccuaaguc ugccccuugg aacagcuucc ugcccccucc uccacccaug      600

cccggaccca gacugggacc cggaaaaccu ggccugaagu ucaacggacc accucccccu      660

ccaccuccuc ccccaccuca ucuccugagc ugcuggcugc cacccuuccc cagcggaccc      720

ccuaucaucc caccaccccc ucccaucugc cccgacagcc uggacgacgc cgaugcccug      780

ggcagcaugc ugaucagcug guacaugagc ggcuaccaca caggauacua caugggcuuc      840

agacagaacc agaaggaggg cagaugcucc cacucccuga acuga                      885


<210> 4
<211> 885
<212> RNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polynucleotide

<400> 4
auggccauga gcagcggagg aagcggagga ggagugccag aacaggaaga uagcgugcug       60

uuucgccggg gcaccggaca aucggacgac agcgauauuu gggacgacac ugcgcucauc      120

aaggccuacg acaaggcggu ggcuucguuc aagcacgcuc ugaagaacgg ggauaucugu      180

gaaaccagcg guaaaccaaa aacuacgccg aaaaggaaac ccgccaaaaa gaacaaguca      240

cagaagaaga auaccgcugc gagcuugcag caguggaagg ugggcgacaa gugcuccgcg      300

auuuggucgg aagaugguug caucuacccg gcaaccaucg ccuccaucga cuuuaagcgg      360

gagacuugcg ucguggucua caccggauac ggcaauagag aggaacagaa ucugucagac      420

cuucugucgc caaucugcga ggucgccaac aauaucgaac aaaacgccca agagaacgag      480

aaugaguccc aaguguccac ggacgaaucg gaaaacucac gguccccugg gaacaaguca      540

gauaacauca agccuaaauc ggcaccaugg aacuccuucc ugccgccucc gccuccgaug      600

ccgggcccgc gccugggacc ggguaaaccc gggcucaagu ucaauggacc gccaccccca      660

cccccgccac cgccgcccca ccuccucucg ugcuggcugc cgccguuccc uuccggaccg      720

ccuaucauuc cgccaccucc accuaucugc ccagacagcc uggaugaugc cgacgcauug      780

ggcuccaugc ucaucucaug guacaugucg ggauaccaua cuggguauua caugggcuuc      840

agacagaacc agaaggaagg acgcuguucc cauagccuga acuag                      885


<210> 5
<211> 1442
<212> RNA
<213> Homo sapiens

<400> 5
ggggccccac gcugcgcacc cgcggguuug cuauggcgau gagcagcggc ggcaguggug       60

gcggcguccc ggagcaggag gauuccgugc uguuccggcg cggcacaggc cagagcgaug      120

auucugacau uugggaugau acagcacuga uaaaagcaua ugauaaagcu guggcuucau      180

uuaagcaugc ucuaaagaau ggugacauuu gugaaacuuc ggguaaacca aaaaccacac      240

cuaaaagaaa accugcuaag aagaauaaaa gccaaaagaa gaauacugca gcuuccuuac      300

aacaguggaa aguuggggac aaauguucug ccauuugguc agaagacggu ugcauuuacc      360

cagcuaccau ugcuucaauu gauuuuaaga gagaaaccug uguugugguu uacacuggau      420

auggaaauag agaggagcaa aaucuguccg aucuacuuuc cccaaucugu gaaguagcua      480

auaauauaga acagaaugcu caagagaaug aaaaugaaag ccaaguuuca acagaugaaa      540

gugagaacuc caggucuccu ggaaauaaau cagauaacau caagcccaaa ucugcuccau      600

ggaacucuuu ucucccucca ccacccccca ugccagggcc aagacuggga ccaggaaagc      660

caggucuaaa auucaauggc ccaccaccgc caccgccacc accaccaccc cacuuacuau      720

caugcuggcu gccuccauuu ccuucuggac caccaauaau ucccccacca ccucccauau      780

guccagauuc ucuugaugau gcugaugcuu ugggaaguau guuaauuuca ugguacauga      840

guggcuauca uacuggcuau uauauggaaa ugcuggcaua gagcagcacu aaaugacacc      900

acuaaagaaa cgaucagaca gaucuggaau gugaagcguu auagaagaua acuggccuca      960

uuucuucaaa auaucaagug uugggaaaga aaaaaggaag uggaaugggu aacucuucuu     1020

gauuaaaagu uauguaauaa ccaaaugcaa ugugaaauau uuuacuggac ucuauuuuga     1080

aaaaccaucu guaaaagacu gagguggggg ugggaggcca gcacgguggu gaggcaguug     1140

agaaaauuug aauguggauu agauuuugaa ugauauugga uaauuauugg uaauuuuaug     1200

agcugugaga aggguguugu aguuuauaaa agacugucuu aauuugcaua cuuaagcauu     1260

uaggaaugaa guguuagagu gucuuaaaau guuucaaaug guuuaacaaa auguauguga     1320

ggcguaugug gcaaaauguu acagaaucua acugguggac auggcuguuc auuguacugu     1380

uuuuuucuau cuucuauaug uuuaaaagua uauaauaaaa auauuuaauu uuuuuuuaaa     1440

aa                                                                    1442


<210> 6
<211> 282
<212> PRT
<213> Homo sapiens

<400> 6
Met Ala Met Ser Ser Gly Gly Ser Gly Gly Gly Val Pro Glu Gln Glu 
1               5                   10                  15      


Asp Ser Val Leu Phe Arg Arg Gly Thr Gly Gln Ser Asp Asp Ser Asp 
            20                  25                  30          


Ile Trp Asp Asp Thr Ala Leu Ile Lys Ala Tyr Asp Lys Ala Val Ala 
        35                  40                  45              


Ser Phe Lys His Ala Leu Lys Asn Gly Asp Ile Cys Glu Thr Ser Gly 
    50                  55                  60                  


Lys Pro Lys Thr Thr Pro Lys Arg Lys Pro Ala Lys Lys Asn Lys Ser 
65                  70                  75                  80  


Gln Lys Lys Asn Thr Ala Ala Ser Leu Gln Gln Trp Lys Val Gly Asp 
                85                  90                  95      


Lys Cys Ser Ala Ile Trp Ser Glu Asp Gly Cys Ile Tyr Pro Ala Thr 
            100                 105                 110         


Ile Ala Ser Ile Asp Phe Lys Arg Glu Thr Cys Val Val Val Tyr Thr 
        115                 120                 125             


Gly Tyr Gly Asn Arg Glu Glu Gln Asn Leu Ser Asp Leu Leu Ser Pro 
    130                 135                 140                 


Ile Cys Glu Val Ala Asn Asn Ile Glu Gln Asn Ala Gln Glu Asn Glu 
145                 150                 155                 160 


Asn Glu Ser Gln Val Ser Thr Asp Glu Ser Glu Asn Ser Arg Ser Pro 
                165                 170                 175     


Gly Asn Lys Ser Asp Asn Ile Lys Pro Lys Ser Ala Pro Trp Asn Ser 
            180                 185                 190         


Phe Leu Pro Pro Pro Pro Pro Met Pro Gly Pro Arg Leu Gly Pro Gly 
        195                 200                 205             


Lys Pro Gly Leu Lys Phe Asn Gly Pro Pro Pro Pro Pro Pro Pro Pro 
    210                 215                 220                 


Pro Pro His Leu Leu Ser Cys Trp Leu Pro Pro Phe Pro Ser Gly Pro 
225                 230                 235                 240 


Pro Ile Ile Pro Pro Pro Pro Pro Ile Cys Pro Asp Ser Leu Asp Asp 
                245                 250                 255     


Ala Asp Ala Leu Gly Ser Met Leu Ile Ser Trp Tyr Met Ser Gly Tyr 
            260                 265                 270         


His Thr Gly Tyr Tyr Met Glu Met Leu Ala 
        275                 280         


<210> 7
<211> 140
<212> RNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polynucleotide

<400> 7
ggacagaucg ccuggagacg ccauccacgc uguuuugacc uccauagaag acaccgggac       60

cgauccagcc uccgcggccg ggaacggugc auuggaacgc ggauuccccg ugccaagagu      120

gacucaccgu ccuugacacg                                                  140


<210> 8
<211> 105
<212> RNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polynucleotide

<400> 8
cggguggcau cccugugacc ccuccccagu gccucuccug gcccuggaag uugccacucc       60

agugcccacc agccuugucc uaauaaaauu aaguugcauc aagcu                     105


<210> 9
<211> 105
<212> RNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polynucleotide

<400> 9
ggguggcauc ccugugaccc cuccccagug ccucuccugg cccuggaagu ugccacucca       60

gugcccacca gccuuguccu aauaaaauua aguugcauca aagcu                      105


<210> 10
<211> 1130
<212> RNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polynucleotide

<400> 10
ggacagaucg ccuggagacg ccauccacgc uguuuugacc uccauagaag acaccgggac       60

cgauccagcc uccgcggccg ggaacggugc auuggaacgc ggauuccccg ugccaagagu      120

gacucaccgu ccuugacacg auggccauga gcagcggagg cagcggcgga ggagugcccg      180

agcaggagga cagcgugcug uucaggagag gcaccggcca gagcgaugac agcgauaucu      240

gggacgauac cgcucugauc aaggccuacg acaaggccgu ggccagcuuc aagcacgccc      300

ugaaaaacgg cgacaucugc gagaccagcg gcaagcccaa gacaaccccc aagagaaagc      360

ccgccaagaa gaauaagagc cagaaaaaga acaccgccgc cagccugcag caguggaagg      420

ugggcgacaa gugcagcgcc aucuggagcg aggacggcug caucuacccc gccaccaucg      480

ccagcaucga cuucaagaga gagaccugcg uggucgugua caccggcuac ggcaacagag      540

aggagcagaa ccugagcgac cugcugagcc ccauuuguga gguggccaau aacaucgaac      600

agaacgccca ggagaacgag aaugaaagcc aggugagcac cgacgagagc gagaacagca      660

gaucuccugg caacaagagc gacaacauca agccuaaguc ugccccuugg aacagcuucc      720

ugcccccucc uccacccaug cccggaccca gacugggacc cggaaaaccu ggccugaagu      780

ucaacggacc accucccccu ccaccuccuc ccccaccuca ucuccugagc ugcuggcugc      840

cacccuuccc cagcggaccc ccuaucaucc caccaccccc ucccaucugc cccgacagcc      900

uggacgacgc cgaugcccug ggcagcaugc ugaucagcug guacaugagc ggcuaccaca      960

caggauacua caugggcuuc agacagaacc agaaggaggg cagaugcucc cacucccuga     1020

acugacgggu ggcaucccug ugaccccucc ccagugccuc uccuggcccu ggaaguugcc     1080

acuccagugc ccaccagccu uguccuaaua aaauuaaguu gcaucaagcu                1130


<210> 11
<211> 1130
<212> RNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polynucleotide

<400> 11
ggacagaucg ccuggagacg ccauccacgc uguuuugacc uccauagaag acaccgggac       60

cgauccagcc uccgcggccg ggaacggugc auuggaacgc ggauuccccg ugccaagagu      120

gacucaccgu ccuugacacg auggccauga gcagcggagg cagcggcgga ggagugcccg      180

agcaggagga cagcgugcug uucaggagag gcaccggcca gagcgaugac agcgauaucu      240

gggacgauac cgcucugauc aaggccuacg acaaggccgu ggccagcuuc aagcacgccc      300

ugaaaaacgg cgacaucugc gagaccagcg gcaagcccaa gacaaccccc aagagaaagc      360

ccgccaagaa gaauaagagc cagaaaaaga acaccgccgc cagccugcag caguggaagg      420

ugggcgacaa gugcagcgcc aucuggagcg aggacggcug caucuacccc gccaccaucg      480

ccagcaucga cuucaagaga gagaccugcg uggucgugua caccggcuac ggcaacagag      540

aggagcagaa ccugagcgac cugcugagcc ccauuuguga gguggccaau aacaucgaac      600

agaacgccca ggagaacgag aaugaaagcc aggugagcac cgacgagagc gagaacagca      660

gaucuccugg caacaagagc gacaacauca agccuaaguc ugccccuugg aacagcuucc      720

ugcccccucc uccacccaug cccggaccca gacugggacc cggaaaaccu ggccugaagu      780

ucaacggacc accucccccu ccaccuccuc ccccaccuca ucuccugagc ugcuggcugc      840

cacccuuccc cagcggaccc ccuaucaucc caccaccccc ucccaucugc cccgacagcc      900

uggacgacgc cgaugcccug ggcagcaugc ugaucagcug guacaugagc ggcuaccaca      960

caggauacua caugggcuuc agacagaacc agaaggaggg cagaugcucc cacucccuga     1020

acugagggug gcaucccugu gaccccuccc cagugccucu ccuggcccug gaaguugcca     1080

cuccagugcc caccagccuu guccuaauaa aauuaaguug caucaaagcu                1130


<210> 12
<211> 500
<212> DNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polynucleotide


<220> 
<221> misc_feature
<222> (1)..(500)
<223> This sequence may encompass 10-500 nucleotides

<220> 
<223> See specification as filed for detailed description of
      substitutions and preferred embodiments

<400> 12
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa       60

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa      120

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa      180

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa      240

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa      300

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa      360

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa      420

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa      480

aaaaaaaaaa aaaaaaaaaa                                                  500


<210> 13
<211> 300
<212> DNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polynucleotide


<220>
<221> misc_feature
<222> (1)..(300)
<223> This sequence may encompass 10-300 nucleotides

<220> 
<223> See specification as filed for detailed description of
      substitutions and preferred embodiments

<400> 13
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa       60

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa      120

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa      180

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa      240

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa      300


<210> 14
<211> 200
<212> DNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polynucleotide


<220>
<221> misc_feature
<222> (1)..(200)
<223> This sequence may encompass 10-200 nucleotides

<220> 
<223> See specification as filed for detailed description of
      substitutions and preferred embodiments

<400> 14
cccccccccc cccccccccc cccccccccc cccccccccc cccccccccc cccccccccc       60

cccccccccc cccccccccc cccccccccc cccccccccc cccccccccc cccccccccc      120

cccccccccc cccccccccc cccccccccc cccccccccc cccccccccc cccccccccc      180

cccccccccc cccccccccc                                                  200


<210> 15
<211> 250
<212> DNA
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polynucleotide


<220> 
<223> See specification as filed for detailed description of
      substitutions and preferred embodiments

<400> 15
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa       60

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa      120

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa      180

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa      240

aaaaaaaaaa                                                             250


