                         SEQUENCE LISTING

<110>  Talkhabifard, Majid
       Shahbazi, Majid
 
<120>  DUAL-SPECIFIC APTAMER TRIGGERING CELL-MEDIATED CYTOTOXICITY TO 
       LYSE HER2-POSITIVE CANCER CELLS

<130>  Ref-1400-02-6950

<150>  US 63133248
<151>  2021-01-01

<160>  16    

<170>  PatentIn version 3.5

<210>  1
<211>  42
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  [Primary] anti-HER2 aptamer that may be used in the dual-specific
       aptamers set forth in SEQ ID NOs: 8 to 14 (i.e., dsA1 to dsA10)

<300>
<301>  Mahlknecht G, Maron R, Mancini M, Schechter B, Sela M, Yarden Y
<302>  Aptamer to ErbB-2/HER2 enhances degradation of the target and 
       inhibits tumorigenic growth
<303>  Proceedings of the National Academy of Sciences
<304>  110
<306>  8174
<307>  2013-05-14

<400>  1
gcagcggtgt gggggcagcg gtgtgggggc agcggtgtgg gg                          42


<210>  2
<211>  34
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  [Primary] anti-CD16 patamer; A truncated form of the anti-CD16 
       aptamer set forth in SEQ ID NO: 3; May be used in the 
       dual-specific aptamers set forth in SEQ ID NOs: 8, 10, 12 and 13 
       (i.e., dsA1, 3, 5, 6, 8 and 9).

<400>  2
ccactgcggg ggtctatacg tgaggaagaa gtgg                                   34


<210>  3
<211>  41
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  [primary] anti-CD16 aptamer that may be used in the dual-specific
       aptamers set forth in SEQ ID NOs: 9, 11 and 14 (i.e., dsA2, 4, 7 
       and 10).

<300>
<301>  Boltz A, Piater B, Toleikis L, Guenther R, Kolmar H, Hock B
<302>  Bi-specific aptamers mediating tumor cell lysis
<303>  Journal of Biological chemistry
<304>  286
<306>  21899
<307>  2011-04-29

<300>
<301>  Boltz A, Piater B, Toleikis L, Guenther R, Kolmar H, Hock B
<302>  Bi-specific aptamers mediating tumor cell lysis
<303>  Journal of Biological Chemistry
<304>  286
<306>  21899
<307>  2011-04-29

<400>  3
ccactgcggg ggtctatacg tgaggaagaa gtgggcaggt c                           41


<210>  4
<211>  7
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleic acid linker used to attach 5' end of the anti-HER2 
       segment to 3' end of the anti-CD16 segment of the dual-specific 
       aptamer set forth in SEQ ID NO: 10 (i.e., dsA3).

<400>  4
aaaaaaa                                                                  7


<210>  5
<211>  13
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleic acid linker used to attach 5' end of the anti-HER2 
       segment to 3' end of the anti-CD16 segment of the dual-specific 
       aptamer set forth in SEQ ID NO: 11 (i.e., dsA4).

<400>  5
aaaaaaaaaa aaa                                                          13


<210>  6
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Nucleic acid linker used to attach one end of the anti-HER2 
       segment to one end of the anti-CD16 segment at the dual-specific 
       aptamers set forth in SEQ ID NOs: 12, 13 and 14 (i.e., dsA5 to 
       10).

<400>  6
aaaaaaaaaa aaaaaaaaaa                                                   20


<210>  7
<211>  20
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Poly-Thymidine sequence that may be hybridized to the nucleic 
       acid linker of the dual-specifc aptamers set forth in SEQ ID NOs:
       12 to 14 (dsA8, 9 and 10), and may be a complementary sequence of
       the nucleic acid linker set forth in SEQ ID NO: 6.

<400>  7
tttttttttt tttttttttt                                                   20


<210>  8
<211>  76
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Dual-specific aptamer (1) referred to as dsA1 throughout the 
       disclosure, wherein the anti-HER2 aptamer (SEQ ID NO: 1) may be 
       disposed at 3' arm and the anti-CD16 aptamer (SEQ ID NO: 2) may 
       be disposed at 5' arm thereof.

<400>  8
ccactgcggg ggtctatacg tgaggaagaa gtgggcagcg gtgtgggggc agcggtgtgg       60

gggcagcggt gtgggg                                                       76


<210>  9
<211>  83
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Dual-specific aptamer (2) referred to as dsA2 throughout the 
       disclosure, wherein the anti-HER2 aptamer (SEQ ID NO: 1) may be 
       disposed at 3' arm and the anti-CD16 aptamer (SEQ ID NO: 3) may 
       be disposed at 5' arm thereof.

<400>  9
ccactgcggg ggtctatacg tgaggaagaa gtgggcaggt cgcagcggtg tgggggcagc       60

ggtgtggggg cagcggtgtg ggg                                               83


<210>  10
<211>  83
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Dual-specific aptamer (3) referred to as dsA3 throughout the 
       disclosure, wherein the anti-HER2 aptamer (SEQ ID NO: 1) may be 
       disposed at 3' arm and the anti-CD16 aptamer (SEQ ID NO: 2) may 
       be disposed at 5' arm thereof.

<400>  10
ccactgcggg ggtctatacg tgaggaagaa gtggaaaaaa agcagcggtg tgggggcagc       60

ggtgtggggg cagcggtgtg ggg                                               83


<210>  11
<211>  96
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Dual-specific aptamer (4) referred to as dsA4 throughout the 
       disclosure, wherein the anti-HER2 aptamer (SEQ ID NO: 1) may be 
       disposed at 3' arm and the anti-CD16 aptamer (SEQ ID NO: 3) may 
       be disposed at 5' arm thereof.

<400>  11
ccactgcggg ggtctatacg tgaggaagaa gtgggcaggt caaaaaaaaa aaaagcagcg       60

gtgtgggggc agcggtgtgg gggcagcggt gtgggg                                 96


<210>  12
<211>  96
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Dual-specific aptamers referred to as dsA5 and dsA8, wherein the 
       anti-HER2 (SEQ ID NO: 1) aptamer may be disposed at 3' arm and 
       the anti-CD16 aptamer (SEQ ID NO: 2) may be disposed at 5' arrm 
       thereof; dsA8 may have a double-stranded linker.

<400>  12
ccactgcggg ggtctatacg tgaggaagaa gtggaaaaaa aaaaaaaaaa aaaagcagcg       60

gtgtgggggc agcggtgtgg gggcagcggt gtgggg                                 96


<210>  13
<211>  96
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Dual-specific aptamers referred to as dsA6 and dsA9, wherein the 
       anti-HER2 aptamer (SEQ ID NO: 1) may be disposed at 5' arm and 
       the anti-CD16 aptamer (SEQ ID NO: 2) may be disposed at 3' arrm 
       thereof; dsA9 may have a double-stranded linker.

<400>  13
gcagcggtgt gggggcagcg gtgtgggggc agcggtgtgg ggaaaaaaaa aaaaaaaaaa       60

aaccactgcg ggggtctata cgtgaggaag aagtgg                                 96


<210>  14
<211>  103
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Dual-specific aptamers referred to as dsA7 and dsA10, wherein the
       anti-HER2 aptamer (SEQ ID NO: 1) may be disposed at 5' arm and 
       the anti-CD16 aptamer (SEQ ID NO: 3) may be disposed at 3' arrm 
       thereof; dsA9 may have a double-stranded linker.

<400>  14
gcagcggtgt gggggcagcg gtgtgggggc agcggtgtgg ggaaaaaaaa aaaaaaaaaa       60

aaccactgcg ggggtctata cgtgaggaag aagtgggcag gtc                        103


<210>  15
<211>  86
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  [Primary] anti-HER2 aptamer as a candidate to be incorporated in 
       the dual-specific aptamers.

<300>
<301>  Liu Z, Duan JH, Song YM, Ma J, Wang FD, Lu X, Yang XD
<302>  Novel HER2 Aptamer Selectively Delivers Cytotoxic Drug to 
       HER2-positive Breast Cancer Cells in Vitro
<303>  Journal of Translational Medicine volume
<304>  10
<306>  4
<307>  2012-07-20

<300>
<301>  Liu Z, Duan JH, Song YM, Ma J, Wang FD, Lu X, Yang XD
<302>  Novel HER2 Aptamer Selectively Delivers Cytotoxic Drug to 
       HER2-positive Breast Cancer Cells in Vitro
<303>  Journal of Translational Medicine
<304>  10
<306>  4
<307>  2012-07-20

<400>  15
aaccgcccaa atccctaaga gtctgcactt gtcattttgt atatgtattt ggtttttggc       60

tctcacagac acactacaca cgcaca                                            86


<210>  16
<211>  40
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  [Primary] anti-HER2 aptamer as a candidate to be incorporated in 
       the dual-specific aptamers.

<300>
<301>  Gijs M, Penner G, Blackler GB, Impens NR, Baatout S, Luxen A, 
       Aerts AM
<302>  Improved aptamers for the diagnosis and potential treatment of 
       HER2-positive cancer
<303>  Pharmaceuticals
<304>  9
<305>  10
<306>  4
<307>  2016-05-10

<400>  16
tctaaaagga ttcttcccaa ggggatccaa ttcaaacagc                             40


