                               SEQUENCE LISTING

<110> ALNYLAM PHARMACEUTICALS, INC.
 
<120> MODIFIED RNA AGENTS WITH REDUCED OFF-TARGET EFFECT

<130> 051058-088343-PCT

<140> PCT/US2017/063078
<141> 2017-11-22

<150> 62/561,514
<151> 2017-09-21

<150> 62/548,589
<151> 2017-08-22

<150> 62/425,907
<151> 2016-11-23

<160> 79    

<170> PatentIn version 3.5

<210> 1
<211> 16
<212> PRT
<213> Homo sapiens

<400> 1
Ala Ala Val Ala Leu Leu Pro Ala Val Leu Leu Ala Leu Leu Ala Pro 
1               5                   10                  15      


<210> 2
<211> 11
<212> PRT
<213> Homo sapiens

<400> 2
Ala Ala Leu Leu Pro Val Leu Leu Ala Ala Pro 
1               5                   10      


<210> 3
<211> 13
<212> PRT
<213> Human immunodeficiency virus

<400> 3
Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Pro Pro Gln 
1               5                   10              


<210> 4
<211> 16
<212> PRT
<213> Drosophila sp.

<400> 4
Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys 
1               5                   10                  15      


<210> 5
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 5
gaaugugaaa gucaucgaca a                                                 21


<210> 6
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 6
uugucgauga cuuucacauu cug                                               23


<210> 7
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 7
gaaugugaaa gucaucgaca a                                                 21


<210> 8
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 8
uugucgauga cuuucacauu cug                                               23


<210> 9
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 9
gaaugugaaa gucaucgaca a                                                 21


<210> 10
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 10
uugucgauga cuuucacauu cug                                               23


<210> 11
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 11
gaaugugaaa gucaucgaca a                                                 21


<210> 12
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 12
uugucgauga cuuucacauu cug                                               23


<210> 13
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 13
gaaugugaaa gucaucgaca a                                                 21


<210> 14
<211> 23
<212> DNA
<213> Artificial Sequence

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

<220>
<223> Description of Combined DNA/RNA Molecule: Synthetic
      oligonucleotide

<400> 14
uugucgatga cuuucacauu cug                                               23


<210> 15
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 15
aacaguguuc uugcucuaua a                                                 21


<210> 16
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 16
uuauagagca agaacacugu uuu                                               23


<210> 17
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 17
aacaguguuc uugcucuaua a                                                 21


<210> 18
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 18
uuauagagca agaacacugu uuu                                               23


<210> 19
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 19
aacaguguuc uugcucuaua a                                                 21


<210> 20
<211> 23
<212> DNA
<213> Artificial Sequence

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

<220>
<223> Description of Combined DNA/RNA Molecule: Synthetic
      oligonucleotide

<400> 20
uuatagagca agaacacugu uuu                                               23


<210> 21
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 21
aacaguguuc uugcucuaua a                                                 21


<210> 22
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 22
uuauagagca agaacacugu uuu                                               23


<210> 23
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 23
aacaguguuc uugcucuaua a                                                 21


<210> 24
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 24
uuauagagca agaacacugu uuu                                               23


<210> 25
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 25
aacaguguuc uugcucuaua a                                                 21


<210> 26
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 26
uuauagagca agaacacugu uuu                                               23


<210> 27
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 27
aacaguguuc uugcucuaua a                                                 21


<210> 28
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 28
uuauagagca agaacacugu uuu                                               23


<210> 29
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 29
uggaagcagu auguugaugg a                                                 21


<210> 30
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 30
uccaucaaca uacugcuucc aaa                                               23


<210> 31
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 31
uggaagcagu auguugaugg a                                                 21


<210> 32
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 32
uccaucaaca uacugcuucc aaa                                               23


<210> 33
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 33
uggaagcagu auguugaugg a                                                 21


<210> 34
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 34
uccaucaaca uacugcuucc aaa                                               23


<210> 35
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 35
uggaagcagu auguugaugg a                                                 21


<210> 36
<211> 23
<212> DNA
<213> Artificial Sequence

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

<220>
<223> Description of Combined DNA/RNA Molecule: Synthetic
      oligonucleotide

<400> 36
uccatcaaca uacugcuucc aaa                                               23


<210> 37
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 37
uggaagcagu auguugaugg a                                                 21


<210> 38
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 38
uccaucaaca uacugcuucc aaa                                               23


<210> 39
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 39
uggaagcagu auguugaugg a                                                 21


<210> 40
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 40
uccaucaaca uacugcuucc aaa                                               23


<210> 41
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 41
uggaagcagu auguugaugg a                                                 21


<210> 42
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 42
uccaucaaca uacugcuucc aaa                                               23


<210> 43
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 43
cugguauuuc cuaggguaca a                                                 21


<210> 44
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 44
uuguacccua ggaaauacca gag                                               23


<210> 45
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 45
aauaaagugc uuugaaaacg u                                                 21


<210> 46
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 46
acguuuucaa agcacuuuau uga                                               23


<210> 47
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 47
cuucuuaaug auugaacaaa a                                                 21


<210> 48
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 48
uuuuguucaa ucauuaagaa gac                                               23


<210> 49
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 49
cuucuuaaug auugaacaaa a                                                 21


<210> 50
<211> 23
<212> DNA
<213> Artificial Sequence

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

<220>
<223> Description of Combined DNA/RNA Molecule: Synthetic
      oligonucleotide

<400> 50
uuuugtucaa ucauuaagaa gac                                               23


<210> 51
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 51
cuucuuaaug auugaacaaa a                                                 21


<210> 52
<211> 23
<212> DNA
<213> Artificial Sequence

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

<220>
<223> Description of Combined DNA/RNA Molecule: Synthetic
      oligonucleotide

<400> 52
uuuugutcaa ucauuaagaa gac                                               23


<210> 53
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 53
cuucuuaaug auugaacaaa a                                                 21


<210> 54
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 54
uuuuguucaa ucauuaagaa gac                                               23


<210> 55
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 55
cuucuuaaug auugaacaaa a                                                 21


<210> 56
<211> 23
<212> DNA
<213> Artificial Sequence

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

<220>
<223> Description of Combined DNA/RNA Molecule: Synthetic
      oligonucleotide

<400> 56
uuuugutcaa ucauuaagaa gac                                               23


<210> 57
<211> 12
<212> RNA
<213> Artificial Sequence

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

<400> 57
uacagucuau gu                                                           12


<210> 58
<211> 12
<212> RNA
<213> Artificial Sequence

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

<400> 58
acauagacug ua                                                           12


<210> 59
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 59
ugacaaaaua acucacuaua a                                                 21


<210> 60
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 60
uuauagugag uuauuuuguc aau                                               23


<210> 61
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 61
gugcacuucg cuucaccucu a                                                 21


<210> 62
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 62
uagaggugaa gcgaagugca cuu                                               23


<210> 63
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 63
gguuaacacg uuuuagauca a                                                 21


<210> 64
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 64
uugaucuaaa acguguuaac cag                                               23


<210> 65
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 65
aacaguguuc uugcucuaua a                                                 21


<210> 66
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 66
uuauagagca agaacacugu uuu                                               23


<210> 67
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 67
gaaugugaaa gucaucgaca a                                                 21


<210> 68
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 68
uugucgauga cuuucacauu cug                                               23


<210> 69
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 69
cugguauuuc cuaggguaca a                                                 21


<210> 70
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 70
uuguacccua ggaaauacca gag                                               23


<210> 71
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 71
cuucuuaaug auugaacaaa a                                                 21


<210> 72
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 72
uuuuguucaa ucauuaagaa gac                                               23


<210> 73
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 73
aagcaagaua uuuuuauaau a                                                 21


<210> 74
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 74
uauuauaaaa auaucuugcu uuu                                               23


<210> 75
<211> 21
<212> RNA
<213> Artificial Sequence

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

<400> 75
aagcaagaua uuuuuauaau a                                                 21


<210> 76
<211> 23
<212> RNA
<213> Artificial Sequence

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

<400> 76
uauuauaaaa auaucuugcu uuu                                               23


<210> 77
<211> 10
<212> DNA
<213> Artificial Sequence

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

<220>
<223> Description of Combined DNA/RNA Molecule: Synthetic
      oligonucleotide

<400> 77
cucactataa                                                              10


<210> 78
<211> 10
<212> DNA
<213> Artificial Sequence

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

<220>
<223> Description of Combined DNA/RNA Molecule: Synthetic
      oligonucleotide

<400> 78
ugcuctataa                                                              10


<210> 79
<211> 10
<212> DNA
<213> Artificial Sequence

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

<220>
<223> Description of Combined DNA/RNA Molecule: Synthetic
      oligonucleotide

<400> 79
tcaucgacaa                                                              10


