Transdominant Rev and Protease Mutant Proteins of HIV-SIV as Potential Antiviral Agents in Vitro and in Vivo (AIDS)
Annual rept. 4 Sep 1992-3 Sep 1993
CALIFORNIA UNIV SAN DIEGO DEPT OF MEDICINE
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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 48 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.
- Medicine and Medical Research