Induction of viral mutation by incorporation of miscoding ribonucleoside analogs into viral RNA
AssigneeUniversity of Washington
InventorsLawrence A. Loeb, James I. Mullins
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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 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.
Claims22
A method of increasing the mutation rate of a virus, comprising administering an RNA nucleoside analog to a virally infected cell, wherein the analog 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, thereby inducing the virus to mutate.
A retroviral particle comprising viral genomic RNA, wherein the viral genomic RNA comprises an RNA nucleoside analog.
A method of increasing the mutation rate of a virus, comprising administering a free base selected from the group comprising adenine, cytosine, guanine, uracil and thymine to a virally infected cell, wherein the base is incorporated by a polymerase into an RNA or DNA copy of a genomic nucleic acid encoding the virus, said base replacing a first natural occurring nucleotide having a first complementary nucleotide wherein said base complements a second nucleotide which is other than the first nucleotide, thereby inducing the virus to mutate.
Dependencies are inferred from the claim text.