Transdominant Rev and Protease Mutant Proteins of HIV/SIV as Potential Antiviral Agents In vitro and In vivo (AIDS)
Abstract
The major goal of this contract is to use gene therapy to target essential genes of HIV/SIV in order to inhibit virus expression. Our initial focus was to generate transdominant mutants of rev and protease genes and to evaluate them in an in vivo model. During the last year, we have expanded our approaches to include use of antisense oligodeoxynucleotides (ODN) directed to the Rev Response Element (RRE) and ribozymes that target viral mRNAs. These latter approaches have yielded very encouraging positive data. Binding of antisense ODN to RRE was optimized according to sequence and in vitro reaction. We demonstrated that this binding indeed interferes with the normal interaction of the Rev protein as well as an important cellular factor (NFRRE) with RRE RNA, and furthermore, phosphorothioate derivative of the antisense ODN efficiently inhibited virus replication. In parallel, a hairpin ribozyme targeting the leader sequence of the HIV genome was shown to inhibit virus expression in a target specific manner. Applications of these approaches will be pursued in the in vivo SCID mouse model in the coming year. HIV/SIV, AIDS, Transdominant Mutants, Rev, Protease, Retrovirus Vector, SCID-Hu Mice Models, Gene Expression, Expression Vectors, RAD I.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 03, 1992
- Accession Number
- ADA269541
Entities
People
- Flossie Wong-staal
Organizations
- University of California, San Diego