Porphyrin-DNA Origami Constructs as Bioscavengers for Organophosphates

The recent use of organophosphate (OP) nerve agents against combatants and civilians in Syria has validated the importance of developing new drugs and biologics that sequester and catalytically degrade organophosphate (OP) nerve agents in the body before they cause morbidity and mortality. We propose to develop a method for the sequestration of OP simulants via porphyrin-DNA constructs. Constructs will be designed and synthesized based upon published approaches and molecular modeling and will be compatible with integration into DNA origami. The DNA origami, in turn, can be modified to meet CBD14-104 requirements for extended serum half-life, lyophilization, and stable shelf life, but equally important, is their biocompatibility, ability to incorporate other constructs for nerve agent sequestration, and ease of production. Successful demonstration of the proposed approach offers the opportunity for development of a novel biopharmaceutical(s) to protect military personnel against OP nerve agents and toxic industrial chemicals.