ANTI-HSV-1 ACTION OF TRIPLEX FORMING OLIGONUCLEOTIDES

THE AIM OF THIS PROJECT IS TO TEST THE FEASIBILITY OF USING TRIPLEX FORMING OLIGONUCLEOTIDES AS ANTIVIRAL AGENTS AGAINSTHERPES SIMPLEX VIRUS TYPE 1. OLIGONUCLEOTIDES HAVE LONG BEEN KNOWN TO BE CAPABLE OF BINDING TO DUPLEX DNA TO FORM TRIPLE HELIX COMPLEXES. ADVANCES IN TRIPLEX TECHNOLOGY NOW ALLOWS THE DESIGN OF TRIPLEX FORMING OLIGONUCLEOTIDES CAPABLE OF BINDING TO COMPLEX SEQUENCES UNDER PHYSIOLOGICAL CONDITIONS. BINDING BY TRIPLEX FORMING OLIGONUCLEOTIDE HAS BEEN SHOWN TO DISRUPT BINDING OF OTHER DNA BINDING PROTEINS AND TO INHIBIT GENE EXPRESSION IN SEVERAL SYSTEMS. WE INTEND TO TEST THE ABILITY OF TRIPLEX FORMING OLIGONUCLEOTIDES TO INHIBIT VIRAL GENE EXPRESSION AND VIRUS GROWTH IN CELL CULTURE. TRIPLEX-FORMING OLIGONUCLEOTIDES WILL BE DESIGNED TO DISRUPT THE PROMOTERS OF THE GENES OF HERPES SIMPLEX VIRUS TYPE I. THE TFOS WILL BE SYNTHESIZED AND ANALYZED FOR THEIR ACTUAL BINDING ABILITY IN VITRO, THEN ASSAYED AS ANTI-HERPES AGENTS IN CELL CULTURE. ANY TFOS CAPABLE OF INHIBITING VIRAL GROWTH IN CELL CULTURE ASSAYS WILL HAVE PASSED PHASE I STUDIES AND PROCEED TO FURTHER EVALUATION AS AN ANTIVIRAL AGENT IN ANIMAL MODELS OF VIRAL INFECTION. THE USE TRIPLEX FORMING OLIGONUCLEOTIDES AS ANTIVIRAL AGENTSIS AN INNOVATIVE APPROACH TO THE DESIGN OF ANTIVIRAL DRUGS. THE AIM OF THIS PROJECT IS TO TEST THE FEASIBILITY OF USING TRIPLEX FORMING OLIGONUCLEOTIDES AS ANTIVIRAL AGENTS AGAINSTHERPES SIMPLEX VIRUS TYPE 1. OLIGONUCLEOTIDES HAVE LONG BEEN KNOWN TO BE CAPABLE OF BINDING TO DUPLEX DNA TO FORM TRIPLE HELIX COMPLEXES. ADVANCES IN TRIPLEX TECHNOLOGY NOW ALLOWS THE DESIGN OF TRIPLEX FORMING OLIGONUCLEOTIDES CAPABLE OF BINDING TO COMPLEX SEQUENCES UNDER PHYSIOLOGICAL CONDITIONS. BINDING BY TRIPLEX FORMING OLIGONUCLEOTIDE HAS BEEN SHOWN TO DISRUPT BINDING OF OTHER DNA BINDING PROTEINS AND TO INHIBIT GENE EXPRESSION IN SEVERAL SYSTEMS. WE INTEND TO TEST THE ABILITY OF TRIPLEX FORMING OLIGONUCLEOTIDES TO INHIBIT VIRAL GENE EXPRESSION AND VIRUS GROWTH IN CELL CULTURE. TRIPLEX-FORMING OLIGONUCLEOTIDES WILL BE DESIGNED TO DISRUPT THE PROMOTERS OF THE GENES OF HERPES SIMPLEX VIRUS TYPE I. THE TFOS WILL BE SYNTHESIZED AND ANALYZED FOR THEIR ACTUAL BINDING ABILITY IN VITRO, THEN ASSAYED AS ANTI-HERPES AGENTS IN CELL CULTURE. ANY TFOS CAPABLE OF INHIBITING VIRAL GROWTH IN CELL CULTURE ASSAYS WILL HAVE PASSED PHASE I STUDIES AND PROCEED TO FURTHER EVALUATION AS AN ANTIVIRAL AGENT IN ANIMAL MODELS OF VIRAL INFECTION. THE USE TRIPLEX FORMING OLIGONUCLEOTIDES AS ANTIVIRAL AGENTSIS AN INNOVATIVE APPROACH TO THE DESIGN OF ANTIVIRAL DRUGS.