Nucleic acid aptamers
The present invention relates to optimized aptamers and methods of using these aptamers.
1. A nucleic acid molecule not more than 90 nucleotides in length comprising an aptamer, wherein the aptamer is aptamer-51 (SEQ ID NO:2373), aptamer-13 (SEQ ID NO:2335), aptamer-14 (SEQ ID NO:2336), aptamer-8 (SEQ ID NO:2330), aptamer-5 (SEQ ID NO:2327), aptamer-3 (SEQ ID NO:2325), aptamer-35 (SEQ ID NO:2366), aptamer-6 (SEQ ID NO:2328), or aptamer-11 (SEQ ID NO:2333).
2. The nucleic acid molecule of claim 1 , wherein the aptamer is aptamer-14 (SEQ ID NO:2336), or aptamer-51 (SEQ ID NO:2373).
3. The nucleic acid molecule of claim 1 , wherein the nucleotides are RNA.
4. The nucleic acid molecule of claim 3 , wherein the RNA includes a modified nucleotide.
5. The nucleic acid molecule of claim 4 , wherein the RNA is chemically modified (2′-fluoropyridines).
6. A conjugate comprising the nucleic acid molecule of claim 1 linked to a therapeutic or diagnostic molecule.
7. The conjugate of claim 6 , wherein the therapeutic molecule is an RNAi molecule.
8. The conjugate of claim 7 , wherein the RNAi molecule is an siRNA molecule or an miRNA molecule.
9. The conjugate of claim 8 , wherein the siRNA specifically targets N×1 NADPH oxidase.
10. A method for delivering a therapeutic or diagnostic molecule to a vascular smooth muscle cell, comprising contacting the cell with the conjugate of claim 6 .
11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and
(i) a nucleic acid molecule not more than 90 nucleotides in length comprising an aptamer, wherein the aptamer is aptamer-51 (SEQ ID NO:2373), aptamer-13 (SEQ ID NO:2335), aptamer-14 (SEQ ID NO:2336), aptamer-8 (SEQ ID NO:2330), aptamer-5 (SEQ ID NO:2327), aptamer-3 (SEQ ID NO:2325), aptamer-35 (SEQ ID NO:2366), aptamer-6 (SEQ ID NO:2328), or aptamer-11 (SEQ ID NO:2333); or
(ii) conjugate comprising the a nucleic acid molecule not more than 90 nucleotides in length comprising an aptamer, wherein the aptamer is aptamer-51 (SEQ ID NO:2373), aptamer-13 (SEQ ID NO:2335), aptamer-14 (SEQ ID NO:2336), aptamer-8 (SEQ ID NO:2330), aptamer-5 (SEQ ID NO:2327), aptamer-2 (SEQ ID NO:2333), aptamer-3 (SEQ ID NO:2325), aptamer-35 (SEQ ID NO:2366), aptamer-6 (SEQ ID NO:2328), or aptamer-11 (SEQ ID NO:2333), linked to a therapeutic or diagnostic molecule.
12. An article of manufacture comprising a solid substrate coated with the molecule of claim 1 .
13. The article of claim 12 , wherein the solid substrate is a stent, catheter, a catheter hub, a catheter port, or a non-degradable implant.