Ribozymes for In Vivo Degradation of G-Nerve Agents

Given the possibility to administer prophylactic doses of protein bioscavengers inactivating OP nerve agents before they reach their acetylcholinesterase target, much attention has been given to proteins such as human butyrylcholinesterase and paraoxonase I. As small nucleic acid catalysts can exhibit triphosphoesterase activities, the identification of new molecules active against nerve agents would constitute a significant breakthrough for the development of a biopharmaceutical approach against OP agents, with rapid optimization of catalytic rate, stability, large-scale production, storage and formulation. In this Phase I, Agave BioSystems proposes to develop novel catalytically active oligonucleotides against G-nerve agents using high throughput selection in E. coli. The development of a high-throughput selection method in E. coli to identify novel RNA molecules able to hydrolyze nerve agents constitutes a promising and innovative approach. Unlike other methods typically used for the de novo creation of new RNA or DNA catalysts, this in vivo approach will directly identify molecules combining favorable binding and dissociation constants, as well as strong catalytic activity.