Transdominant Rev and Proteased Mutant Proteins of HIV/SIV as Potential Antiviral Agents in Vitro and in Vivo (Aids)
Technical Report,04 Apr 1990,03 Feb 1994
CALIFORNIA UNIV SAN DIEGO LA JOLLA LA JOLLA United States
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The major goal of this contract is to use gene therapy to target essential genes of HIVSIV 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. Subsequent efforts have led us to develop a ribozyme gene therapy approach that seems promising. The first HIV-1 ribozyme that we have analyzed was engineered to cleave the 51-leader sequence of HIV-1 HXB2 clone RNA at position 111112 from the cap site. We have compiled data which established that this ribozyme, when delivered by a murine retroviral vector and expressed stably in Jurkat cells or PBL, is able to confer resistance to infection by diverse strains of HIV-1, including uncloned clinical isolates. HIVSIV, AIDS, Transdominant mutants, Rev, Protease, Retrovirus, Vectorf SCID-HU Mice models.