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 to evaluate them in an in vivo model. During the last two years, 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. The ribozyme approach, in particular, has yielded extremely encouraging positive data. We showed that a hairpin ribozyme designed to cleave HIV-1 RNA in the 5' leader sequence suppressed virus expression in Hela cells co-transfected with proviral DNA. Human CD4+ T cell lines (Jurkat and Molt 4/8) transducted by a retroviral vector expressing ribozyme were resistant to challenge from diverse strains of HIV-1, including an uncloned clinical isolate. Transduction of primary lymphocytes with the ribozyme vector also completely blocked infection by HIV-1.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 30, 1993
- Accession Number
- ADA276142
Entities
People
- Flossie Wong-staal
Organizations
- University of California, San Diego