SBIR-STTR Award

Synergen, Inc.'s proposed research will develop, through recombinant DNA methods, new agents to control dental plaque. These will consist of an enzymatic moiety of therapeutic value fused with 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 betagalactosidase. 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 clinical trials.Adheson technology can be adapted to other dental technologies, including controlled-release delivery systems.National Institute of Dental Research (NIDR)

This research will continue to apply recombinant DNA methods to develop antiplaque agents that will be effective against gingivitis and periodontal disease. These agents will consist of (1) an enzymatic domain of therapeutic value fused to (2) an adhesive domain that binds specifically and strongly to dental surfaces. The latter domains are termed adheson sequences and the resulting technology, adheson technology. Using adheson technology to immobilize therapeutic enzymes at the tooth's surface will increase local concentrations and extend residence times, thereby enhancing their therapeutic or prophylactic value. During Phase I, Synergen, Inc., validated adheson technology by producing a model protein that combines an adheson sequence with the enzyme, beta-galactosidase. The model protein is enzymatically active and binds to hydroxylapatite; phosphorylation of the adheson domain enhances binding to hydroxylapatite. Model protein bound to hydroxylapatite has a half-life adequate to provide therapeutically useful residence times.During Phase II, adheson sequences will be fused to enzymes known to prevent or retard the formation of dental plaque. High-level production systems will be developed to produce fusion proteins in amounts adequate for in vitro testing. Methods for efficiently phosphorylating fusion proteins and for increasing the number of available binding sites will also be explored.

Anticipated Results:
Antidental plaque preparations containing the recombinant proteins developed from this research will be effective against gingivitis and periodontal disease. The underlying technology, which involves immobilizing therapeutic enzymes with tissue-specific adhesives, also has broader applications.National Institute Of Dental Research (NIDR)