CATALYTIC RNA AND DNA AS ANTIHIV 1 THERAPEUTIC AGENTS

Scripps Research Institute, La Jolla CA

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Abstract

DESCRIPTION: (Adapted from Applicant's Abstract) The proposed research aims to apply the DNA cleaving RNA enzymes and RNA cleaving DNA enzymes to HIV-1 and FIV targets, culminating in an assessment of antiviral efficacy in FIV infected cells. A program of medicinal biochemistry will be carried out, addressing issues of compound potency, specificity, stability, delivery, and formulation. The RNA cleaving DNA enzymes will receive the greatest attention. These compounds are comprised of only 30 deoxynucleotides, yet have a catalytic efficiency exceeding that of any other known nucleic acid enzyme. DNA enzymes will be designed to cleave target sites within FIV RNA, then tested in feline lymphocytic cells that have been infected with FIV. DNA enzymes also will be designed to cleave mRNAs encoding various HIV-1 co-receptor proteins, These molecule will be made available to the AIDS research community for use as a chemical "knock out" agents in studying the role that beta chemokine receptors play in HIV-1 pathogenesis. Finally, in vitro evolution methods will be used to develop DNA enzymes with glycosidase activity. Such molecules might be used to cleave cell-surface glycoproteins , such as the HIV-1 gp 120 envelope glycoproteins.