Nucleic acid aptamers
The present invention relates to optimized aptamers and methods of using these aptamers.
1. A nucleic acid molecule consisting of the nucleic acid sequence aptamer A10-3.2 (5′-GGGAGGACGAUGCGGAUCAGCCAUGUUUACGUCACUCCU-3′ (SEQ ID NO:5)).
2. A conjugate comprising the nucleic acid molecule of claim 1 linked to a therapeutic or diagnostic molecule.
3. The conjugate of claim 2 , wherein the therapeutic molecule is a siRNA molecule having a guide strand and a passenger strand that form a duplex, wherein the guide strand is linked to the nucleic acid molecule, and wherein the guide strand or passenger strand comprises the nucleic acid sequence 5′-GGGCGGCUUUGCCAAGUGUUU-3′ (SEQ ID NO:6) or 5′-GGGCGGCUUUGCCAAGUGCUU-3′ (Plk1, SEQ ID NO:7) or 5′-GGGCGGCUUUGCCAAGUGU-3′ (SEQ ID NO:8) or 5′-GCACUUGGCAAAGCCGCCCUU-3′ (SEQ ID NO:10).
4. A conjugate comprising the nucleic acid molecule of Stem Loop Chimera SEQ ID NO:21.
5. The conjugate of claim 2 , which further comprises a PEG molecule, wherein the PEG molecule has an average molecular weight of about 10 to 100 kDa in size.
6. A method for delivering a therapeutic or diagnostic molecule to a cell having a PMSA receptor, comprising contacting the cell with the conjugate of claim 2 .
7. A pharmaceutical composition comprising the conjugate of claim 2 and a pharmaceutically acceptable carrier.
8. A method for treating a patient having prostate cancer comprising administering a conjugate of claim 2 to the patient.
9. A conjugate comprising a nucleic acid molecule not more than 45 nucleotides in length comprising the nucleic acid sequence 5′-n 1 n 2 n 3 CGGAUCAGCn 4 n 5 n 6 GUUUA-3′ (SEQ ID NO:1), wherein each n x can be present or absent, wherein when present each n x represents any nucleotide linked to a therapeutic molecule, wherein the therapeutic molecule is an siRNA.
10. The conjugate of claim 9 , wherein the therapeutic molecule is a siRNA molecule having a guide strand and a passenger strand that form a duplex, wherein the guide strand is linked to the nucleic acid molecule, and wherein the guide strand or passenger strand comprises the nucleic acid sequence 5′-GGGCGGCUUUGCCAAGUGUUU-3′ (SEQ ID NO:6) or 5′-GGGCGGCUUUGCCAAGUGCUU-3′ (Plk1, SEQ ID NO:7) or 5′-GGGCGGCUUUGCCAAGUGU-3′ (SEQ ID NO:8) or 5′-GCACUUGGCAAAGCCGCCCUU-3′ (SEQ ID NO:10).
11. The conjugate of claim 9 , which further comprises a PEG molecule covalently bound to the conjugate, wherein the PEG molecule has an average molecular weight of about 10 to 100 kDa in size.
12. A method for delivering a therapeutic or diagnostic molecule to a cell having a PMSA receptor, comprising contacting the cell with the conjugate of claim 9 .
13. A pharmaceutical composition comprising the conjugate of claim 9 and a pharmaceutically acceptable carrier.
14. A method for treating a patient having prostate cancer comprising administering a conjugate of claim 9 to the patient.
15. The conjugate of claim 4 , which further comprises a PEG molecule covalently bound to the conjugate, wherein the PEG molecule has an average molecular weight of about 10 to 100 kDa in size.