Induction of viral mutation by incorporation of miscoding ribonucleoside analogs into viral RNA
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Abstract
The present invention is directed to the identification and use of ribonucleoside analogs to induce the mutation of an RNA virus, including BVDV, HIV and HCV, or a virus which otherwise replicates through an RNA intermediate. The increase in the mutation rate of the virus results in reduced viability of progeny generations of the virus, thereby inhibiting viral replication. In addition to these methods and related compositions, the invention provides methods and combinatorial chemistry libraries for screening ribonucleoside analogs for mutagenic potential.
51 Citations
67 Claims
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1-18. -18. (canceled)
- 19. A viral particle comprising viral genomic RNA, wherein the viral genomic RNA comprises an RNA nucleoside analog.
- 22. A population of cells comprising a highly variable population of replicated homologous viral nucleic acids.
- 25. A cell comprising a viral genomic nucleic acid, an RNA analog, a cellular mRNA analog and a viral genomic RNA analog.
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30-40. -40. (canceled)
- 41. A pharmaceutical composition comprising a therapeutically effective dose of an RNA nucleoside analog, wherein the analog is one that in a infected cell with a virus of interest is incorporated by a polymerase into an RNA copy of a genomic nucleic acid encoding the virus, said analog replacing a first natural occurring nucleotide having a first complementary nucleotide wherein said analog complements a second nucleotide which is other than the first nucleotide together with a pharmaceutically acceptable carrier.
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45-66. -66. (canceled)
Specification