Methods and compositions for RNAi mediated inhibition of gene expression in mammals
OwnerMark A. Kay, Anton McCaffreyinventors
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Abstract
Methods and compositions are provided for modulating, e.g., reducing, coding sequence expression in mammals. In the subject methods, an effective amount of an RNAi agent, e.g., an interfering ribonucleic acid (such as an siRNA or shRNA) or a transcription template thereof, e.g., a DNA encoding an shRNA, is administered to a non-embryonic mammal, e.g., via a hydrodynamic administration protocol. Also provided are RNAi agent pharmaceutical preparations for use in the subject methods. The subject methods and compositions find use in a variety of different applications, including academic and therapeutic applications.
Claims37
A method of reducing expression of a coding sequence in a target cell of a non-embryonic mammal, said method comprising:
- administering to said mammal an effective amount of an RNAi agent specific for said coding sequence to reduce expression of said coding sequence.
A pharmaceutical preparation comprising an RNAi agent in a pharmaceutically acceptable delivery vehicle.
A non-embryonic non-human animal comprising an RNAi agent.
A method for introducing a ribonucleic acid into a target cell of a vascularized multi-cellular organism, said method comprising:
- administering said ribonucleic acid as a naked ribonucleic acid into the vascular system of said organism to introduce said ribonucleic acid into said target cell of said vascularized multi-cellular organism.
A method for introducing a nucleic acid into a target cell of a vascularized multi-cellular organism, said method comprising:
- hydrodynamically administering to said vascularized multi-cellular organism an aqueous formulation comprising said nucleic acid as a naked nucleic acid and an RNase inhibitor to introduce said nucleic acid into said target cell.
A kit for use in delivering a nucleic acid to a target cell of a vascularized multi-cellular organism, said kit comprising:
- said nucleic acid present as a naked nucleic acid;
- and
- an RNase inhibitor;
A method of determining the activity of an RNA virus candidate modulatory agent, said method comprising:
- (1) hydrodynamically administering to a vascularized multicellular animal:
- (a) a nucleic acid construct that includes either:
- (i) a RNA molecule that includes at least one regulatory element of said RNA virus operably linked to a reporter element;
- or
- (ii) a DNA molecule capable of being transcribed into said RNA molecule;
- and
- (b) said candidate modulatory agent;
- and
- (2) observing the effect of said modulatory agent on the activity of said construct is to determine the activity of said candidate modulatory agent.
Dependencies are inferred from the claim text.