ANTIPLAQUE PROTEINS VIA GENETIC ENGINEERING

SYNERGEN, INC.'S PROPOSED RESEARCH WILL DEVELOP, THROUGH RECOMBINANT DNA METHODS, NEW AGENTS TO CONTROL DENTAL PLAQUETHESE WILL CONSIST OF AN ENZYMATIC MOIETY OF THERAPEUTIC VALUE FUSED WIH AN ADHESIVE PEPTIDE THAT BINDS SPECIFICALLY AND STRONGLY TO DENTAL SURFACES. THE LATTER ARE TERMED ADHESON SEQUENCES, AND THE RESULTING TECHNOLOGY, ADHESON TECHNOLOGY. USING ADHESON TECHNOLOGY TO IMMOBILIZE ENZYMES AT THE TOOTH SURFACE WILL INCREASE LOCAL CONCENTRATIONS OF THE ENZYMES AND EXTEND THEIR RESIDENCE TIMES, THEREBY ENHANCING THEIR THERAPEUTIC OR PROPHYLACTIC VALUE. THE PHASE I FEASIBILITY STUDY WILL PRODUCE A SET OF PROTOTYPE FUSION PROTEINS, EACH OF WHICH COMBINES AN ADHESON SEQUENCE WITH THE ENZYME BETA-GALACTOSIDASE. FOR EACH FUSION, SYNERGEN, INC. WILL MEASURE, IN VITRO, THE BINDING TO DENTAL SURFACES AND THE ACTIVITY OF THE BETA-GALACTOSIDASE. BY THE END OF PHASE I, THE SEQUENCES THAT BIND MOST EFFICIENTLY AND SUPPORT ENZYME ACTIVITY WILL BE IDENTIFIED. IN PHASE II, THOSE SEQUENCES WILL BE COMBINED WITH THERAPEUTIC ENZYMES AND THESE SECOND-GENERATION FUSIONS EVALUATED IN VITRO. THE MOST PROMISING WILL BE EVALUATED IN ANIMAL MODELS, THEN IN CLILNICAL TRIALS. ADHESON TECHNOLOGY CAN BE ADAPTED TO OTHER DENTAL TECHNOLOGIES, INCLUDING CONTROLLED-RELEASE DELIVERY SYSTEMS.