HER2 nucleic acid aptamers

1. An aptamer molecule not more than 55 nucleotides in length comprising the nucleic acid sequence 5′-GGGAGGACGAUGCGG-R 1 -CAGACGACUCGCCCGA-3′ (SEQ ID NO: 45), wherein R 1 is

(A1, SEQ ID NO: 1)

GACUGUACGGGGCUCUGUG,

(A2, SEQ ID NO: 2)

GACUGUAUGGGGCUCUGUG,

(A3, SEQ ID NO: 3)

GACUGUACGGGCUCUGUG,

(A4, SEQ ID NO: 4)

UCUCAGUAGUGGGCCUGCUG,

(A5, SEQ ID NO: 5)

GACUGUAUGGGCUCUGUG,

(A6, SEQ ID NO: 6)

GACUGUAUCGGGGCUCUGUG,

(A-consensus, SEQ ID NO: 7)

GACUGUAYGGGGCUCUGUG,

(D1, SEQ ID NO: 8)

AUGUAUGUUGGGAGCCACGC,

(D2, SEQ ID NO: 9)

CUGUAUGUUGGUAGCCACGC,

(D3, SEQ ID NO: 10)

UCUGUGUGGGAUGUGGCCC,

(D-consensus, SEQ ID NO: 11)

AUGUAUGUUGGGAGCCACGC,

(B1, SEQ ID NO: 12)

UCUGUUGUGCUUGAUAUGCCC,

(B2, SEQ ID NO: 13)

UGGUGUGUCAAGGUACGCGC,

(B3, SEQ ID NO: 14)

UCUGCUGUGCUUGAUAUGCCC,

(B-consensus, SEQ ID NO: 15)

UCUGUUGUGCUUGAUAUGCCC,

(C1, SEQ ID NO: 16)

CUGUCUACCUUCUACUGCCG,

(C2, SEQ ID NO: 17)

CCAGUUUACCUUACACUCGC,

(C3, SEQ ID NO: 18)

CGAUGCUUACGUGCACGCGC,

(C4, SEQ ID NO: 19)

CUGUCUACCUUCUACUGCCC,

(C5, SEQ ID NO: 20)

UUGUCUACCUUCUACUGCCG,

(C-consensus, SEQ ID NO: 21)

CUGUCUWMGCUUCUACUGCCG,

(E1, SEQ ID NO: 22)

UCCUGUCGUCUGUUCGUCCC,

(E2, SEQ ID NO: 23)

CCGUGUCGUCUGUACUGCCC,

or

(E-consensus, SEQ ID NO: 24)

UCCUGUCGUYUGKUCSKCCC.

2. The aptamer of claim 1 , wherein the nucleic acid molecule comprises nucleic acid 5′-GGGAGGACGAUGCGGGACUGUAYGGGGCUCUGUGCAGACGACUCGCCCGA-3′ (SEQ ID NO: 25); 5′-GGGAGGACGAUGCGGUCUGUUGUGCUUGAUAUGCCCCAGACGACUCGCCCGA-3′ (SEQ ID NO: 26); 5′-GGGAGGACGAUGCGGCUGUCUWMGCUUCUACUGCCGCAGACGACUCGCCCGA-3′ (SEQ ID NO: 27); 5′-GGGAGGACGAUGCGGAUGUAUGUUGGGAGCCACGCCAGACGACUCGCCCGA-3′ (SEQ ID NO: 28); or 5′-GGGAGGACGAUGCGGUCCUGUCGUYUGKUCSKCCCCAGACGACUCGCCCGA-3′ (SEQ ID NO: 29).

3. A conjugate comprising the aptamer of claim 1 operably linked to a Bcl-2 RNAi molecule.

4. The conjugate of claim 3 , wherein the Bcl-2 RNAi molecule comprises nucleic acid 5′-GCUGUCACAGAGGGGCUACUU-3′ (SEQ ID NO: 30).

5. The conjugate of claim 4 , consisting of 5′-GGGAGGACGAAUGCGGGACUGUACGGGGCUCUGUGCAGACGACUCGCCCGAGCUGUCACAGAGGGGCUACUU-3′ (A1-Bcl-2, SEQ ID NO:32); 5′-GGGAGGACGAUGCGGGACUGUAUGGGGCUCUGUGCAGACGACUCGCCCGAGCUGUCACAGAGGGGCUACUU-3′ (A2-Bcl-2, SEQ ID NO:33); 5′-GGGAGGACGAUGCGGGACUGUACGGGCUCUGUGCAGACGACUCGCCCGAGCUGUCACAGAGGGGCUACUU-3′ (A3-Bcl-2, SEQ ID NO:34); 5′-GGGAGGACGAUGCGGUCUGUUGUGCUUGAUAUGCCCCAGACGACUCGCCCGAGCUGUCACAGAGGGGCUACUU-3′ (B1-Bcl-2, SEQ ID NO:35); 5′-GGGAGGACGAUGCGGUGGUGUGUCAAGGUACGCGCCAGACGACUCGCCCGAGCUGUCACAGAGGGGCUACUU-3′ (B2-Bcl-2, SEQ ID NO:36); 5′-GGGAGGACGAUGCGGUCUGCUGUGCUUGAUAUGCCCCAGACGACUCGCCCGAGCUGUCACAGAGGGGCUACUU-3′ (B3-Bcl-2, SEQ ID NO:37); 5′-GGGAGGACGAUGCGGCUGUCUACCUUCUACUGCCGCAGACGACUCGCCCGAGCUGUCACAGAGGGGCUACUU-3′ (C1-Bcl-2, SEQ ID NO:38); 5′-GGGAGGACGAUGCGGCGAUGCUUACGUGCACGCGCCAGACGAACUCGCCCGAGCUGUCACAGAGGGGCUACUU-3′ (C2-Bcl-2, SEQ ID NO:39); 5′-GGGAGGACGAUGCGGCGAUGCUUACGUGCACGCGCCAGACGACUCGCCCGAGCUGUCACAGAGGGGCUACUU-3′ (C3-Bcl-2, SEQ ID NO:40); 5′-GGGAGGACGAUGCGGAUGUAUGUUGGGAGCCACGCCAGACGACUCGCCCGAGCUGUCACAGAGGGGCUACUU-3′ (D1-Bcl-2, SEQ ID NO:41); 5′-GGGAGGACGAUGCGGCUGUAUGUUGGUAGCCACGCCAGACGACUCGCCCGAGCUGUCACAGAGGGGCUACUU-3′ (D2-Bcl-2, SEQ ID NO:42); 5′-GGGAGGACGAUGCGGUCUGUGUGGGAUGUGGCCCCAGACGACUCGCCCGAGCUGUCACAGAGGGGCUACUU-3′ (D3-Bcl-2, SEQ ID NO:43); or 5′-GGGAGGACGAUGCGGUCCUGUCGUCUGUUCGUCCCAGACGACUCGCCCGAGCUGUCACAGAGGGGCUACUU-3′ (E1-Bcl-2, SEQ ID NO:44).

6. The conjugate of claim 4 hybridized to 5′-GUAGCCCCUCUGUGACAGCUU-3′ (SEQ ID NO:31).

7. A complex comprising the aptamer of claim 1 linked to a therapeutic or diagnostic molecule.

8. The complex of claim 7 , wherein the aptamer is linked to a therapeutic molecule, and the therapeutic molecule is a siRNA molecule.

9. The complex of claim 8 , wherein the siRNA has a guide strand and a passenger strand, and wherein the guide strand is linked to the nucleic acid molecule.

10. The complex of claim 7 , which further comprises a PEG molecule.

11. The complex of claim 10 , wherein the PEG molecule has an average molecular weight of about 10 to 100 kDa in size.

12. A nucleic acid molecule encoding the aptamer of claim 1 .

13. An expression cassette comprising the molecule of claim 12 .

14. The expression cassette of claim 13 , further comprising a promoter.

15. A viral vector comprising the expression cassette of claim 13 .

16. A pharmaceutical composition comprising the aptamer of claim 1 .

17. A method for delivering a therapeutic or diagnostic molecule to a cell having a HER2 receptor, comprising contacting the cell with the aptamer of claim 1 .

18. A method for treating a patient having cancer comprising administering the aptamer of claim 1 to the patient.

19. The method of claim 18 , further comprising administering Herceptin.