Chemically modified AMPA receptor RNA aptamers
View Patent ↗Disclosed is an RNA aptamer, a synthetic oligonucleotide of 2′-fluoro-modified A, U, and C nucleotides, with improved stability compared to its unmodified counterpart. Like the unmodified aptamer, however, the modified version is a potent glutamate receptor antagonist. Additionally, the RNA aptamers described herein are water soluble by nature, and generally exhibit nano- to micromolar potency making them potential therapeutic agents for the treatment of neurological disorders involving glutamate receptor activity.
1. A synthetic RNA oligonucleotide consisting of a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 11, wherein A, C, and U triphosphates (ATPs, CTPs and UTPs) of said oligonucleotide are 2′-fluoro-modified.
2. A synthetic RNA oligonucleotide comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 11, wherein A, C, and U triphosphates (ATPs, CTPs and UTPs) of said oligonucleotide are 2′-fluoro-modified.
3. The synthetic RNA oligonucleotide of claim 1 , wherein said oligonucleotide is ribonuclease resistant.
4. The synthetic RNA oligonucleotide of claim 2 , wherein said oligonucleotide is ribonuclease resistant.
5. A pharmaceutical composition comprising the synthetic RNA oligonucleotide of claim 1 .
6. The pharmaceutical composition of claim 5 , further comprising a pharmaceutically acceptable carrier.
7. A pharmaceutical composition comprising the synthetic RNA oligonucleotide of claim 2 .
8. The pharmaceutical composition of claim 7 , further comprising a pharmaceutically acceptable carrier.
9. A method for reducing neuropathic pain in a mammal comprising administering a therapeutically effective amount of a synthetic RNA oligonucleotide of claim 1 .
10. A method for reducing neuropathic pain in a mammal comprising administering a therapeutically effective amount of a synthetic RNA oligonucleotide of claim 2 .
11. A method for reducing neuropathic pain in a mammal comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 5 .
12. A method for reducing neuropathic pain in a mammal comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 6 .
13. A method for reducing neuropathic pain in a mammal comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 7 .
14. A method for reducing neuropathic pain in a mammal comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 8 .
15. A method for treating neurological diseases and disorders selected from the group consisting of epilepsy and amyotrophic lateral sclerosis comprising administering to a mammal a therapeutically effective amount of a synthetic RNA oligonucleotide of claim 1 .
16. A method for treating neurological diseases and disorders selected from the group consisting of epilepsy and amyotrophic lateral sclerosis comprising administering to a mammal a therapeutically effective amount of a synthetic RNA oligonucleotide of claim 2 .