Methods and compositions for RNAi mediated inhibition of gene expression in mammals

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.

Description

[0001] Pursuant to 35 U.S.C. .sctn.119 (e), this application claims priority to the filing date of the U.S. Provisional Patent Application Serial No. 60 / 307,411 filed Jul. 23, 2001 and U.S. Provisional Patent Application Serial No. 60 / 360,664 filed Feb. 27, 2002; the disclosures of which are herein incorporated by reference.[0002] 1. Field of the Invention[0003] The field of this invention is RNAi.[0004] 2. Background of the Invention[0005] Double-stranded RNA induces potent and specific gene silencing through a process referred to as RNA interference (RNAi) or posttranscriptional gene silencing (PTGS). RNAi is mediated by RNA-induced silencing complex (RISC), a sequence-specific, multicomponent nuclease that destroys messenger RNAs homologous to the silencing trigger. RISC is known to contain short RNAs (approximately 22 nucleotides) derived from the double-stranded RNA trigger.[0006] RNAi has become the method of choice for loss-of-function investigations in numerous systems inclu...

AI Technical Summary

Problems solved by technology

To date, the Applicants are not aware of any report of successful application of RNAi technology to non-embryonic mammalian organisms.

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