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Abstract
Grant Number: 1R43AI052883-01A1 PI Name: HERWEIJER, HANS PI Email: hans.herweijer@genetransfer.com PI Title: DIRECTOR OF PRECLINICAL RESEARCH Project Title: Smallpox treatment by RNA Interference Abstract: DESCRIPTION (provided by applicant): While eradicated as an endemic disease, smallpox remains a threat to human health because it may be used by bioterrorists. The potential spread of variola virus or recombinant forms of variola or other poxviruses requires the development of novel therapeutic approaches. We propose to develop and utilize RNA interference (RNAi) technology to treat smallpox. RNAi is accomplished by the introduction of double-stranded RNA into the cell, resulting in sequence specific degradation of the target mRNA. Application of short (21-25 bp) double stranded RNA (siRNA) also induces effective RNAi and limits non-specific effects. We have recently demonstrated that siRNA can be efficiently introduced into mammalian cells in vivo, and can be used to modulate gene expression. In this SBIR Phase I grant proposal, we will determine if poxvirus gene expression can be inhibited by siRNA. For these experiments, we will use vaccinia virus as a highly relevant model for variola virus. Several genes from different viral pathways (transcription, replication, virion formation, virulence) will be targeted in vitro. Effects upon target gene expression and viral replication will be measured. These experiments should demonstrate the feasibility of using siRNA for smallpox therapy or prophylaxis.
Thesaurus Terms:
Poxviridae disease, gene induction /repression, genetic technique, microorganism disease chemotherapy, smallpox virus, technology /technique development, virus genetics
DNA replication, biological model, gene expression, genetic transcription, virion, virulence, virus infection mechanism, virus protein, virus replication
bioterrorism /chemical warfare, molecular cloning, plasmid, polymerase chain reaction, protein quantitation /detection, transfection /expression vector, vaccinia virus
Institution: MIRUS CORPORATION 505 S ROSA RD, #104 MADISON, WI 53711 Fiscal Year: 2003 Department: Project Start: 15-SEP-2003 Project End: 29-FEB-2004 ICD: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES IRG: ZRG1