Operational Technologies Corporation proposes to develop non-immunogenic DNA aptamers against unfractionated snake, scorpion, spider, and insect venoms as well as snake phospholipase A2 (PLA2) and melittin (major components of venoms) in Phase 1. OpTech will then test each of the final round aptamers for the ability to inhibit PLA2 and prevent cell lysis due to various venoms in a human fibroblast culture. OpTech will also investigate the feasibility of developing aptamer-dendrimers to add weight and slow aptamer degradation and clearance in vivo during Phase 1. Various aptamers against each class of venom will be conjugated to the ends of existing dendrimers or built into the structure of self-assembling dendrimers to create a ?Universal? scavenger. In Phase 2 OpTech will test its aptamer-dendrimers in a murine challenge model and begin to seek FDA approval with the aid or the Texas BioAlliance. During Phase 2 OpTech will also develop aptamers against the more minor, albeit important, components of venoms (e.g., isolated ion channel blockers etc.) and experiment with DNAzyme development to breakdown non-enzymatic components of venoms (polyamines, histamine). Promising aptamers developed early in Phase 2 will also be added to dendrimers for further animal studies to determine if they enhance protective effects.
