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US 10,370,662 B2Granted
Replication capable rAAV vectors encoding inhibitory siRNA and methods of their use
AssigneeCity of Hope
InventorsKamehameha K. Wong, Jr., Cam Mroske, Saswati Chatterjee
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Abstract
In some embodiments, an antiviral vector is provided. The antiviral vector includes a replication competent adeno-associated virus (AAV) and an inhibitory expression cassette that includes a nucleotide sequence that encodes an RNAi molecule that inhibits expression of a targeted helper virus (THV) gene. The THV gene may be part of an Adenovirus (Ad) genome, a Human Papillomavirus (HPV) genome, a Human Herpes Virus (HHV) genome, or a Vaccinia virus (VV) genome.
Claims13
A pharmaceutical composition comprising:
- (i) one or more antiviral vectors, each comprising
- an inhibitory expression cassette;
- and
- a replication competent adeno-associated virus (AAV);
- and
- (ii) a pharmaceutically acceptable carrier,
- wherein the inhibitory expression cassette comprises a nucleotide sequence that encodes an RNAi molecule that inhibits expression of a targeted helper virus (THV) gene, and
- wherein the RNAi molecule is an shRNA comprising a sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:57, SEQ ID NO:58, and SEQ ID NO:59.
5 more elements
A method of producing an antiviral vector comprising:
- culturing the antiviral vector with a population of cells infected with a first THV, such that the antiviral vector co-infects the population of cells;
- and
- isolating the antiviral vector after at least one full infectious cycle;
- wherein the antiviral vector comprises a replication competent AAV virus and a nucleotide sequence that encodes an RNAi molecule that inhibits expression of a targeted helper virus (THV) gene, and
- wherein the RNAi molecule is an shRNA comprising a sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:57, SEQ ID NO:58, and SEQ ID NO:59.
2 more elements
Dependencies are inferred from the claim text.