SBIR Phase I:Novel System for Targeting Nanobodies

This Small Business Innovation Research (SBIR) Phase I project has the goal of creating a system that, while being inexpensive and simple to use, will be able to generate variable domains of heavy chain-only llama antibodies (also called VHHs, or nanobodies) targeted to antigens of interest in vitro. This system will not require llama vaccinations and will use universal pre-fabricated libraries for fast isolation of nanobodies with required specificities. To prove the concept, it is proposed to create the first set of nanobodies targeted at the catalytic domain of botulinum neurotoxin A, which is listed among the most potent biothreat agents and, simultaneously, is used as a miracle drug in neurology and cosmetology. The broader/commercial impacts of this research are expected in the areas of biodefense and medicine. Our system will allow fast and inexpensive development of nanobodies produced in E. coli and specifically targeted to antigens of choice. Availability of such small and stable antigen-targeted molecules will stimulate their use as substitutes for antibodies in multiple detection and diagnostic techniques. Our system will provide potential for development of new ways for isolation, immobilization and/or inactivation of biologically active agents. Additionally, the ability to quickly generate nanobodies with new specificities will speed up efforts to develop nanobodies into a new class of drugs for treatment of both infectious and non infectious diseases.