SBIR Phase I: Novel System for Targeting Nanobodies

这个小型企业创新研究（SBIR）第一阶段项目的目标是创建一个系统，该系统虽然价格低廉且易于使用，但将能够在体外产生靶向感兴趣抗原的仅重链骆驼抗体（也称为VHH或纳米抗体）的可变结构域。该系统将不需要美洲驼疫苗接种，并且将使用通用预制库来快速分离具有所需特异性的纳米抗体。为了证明这一概念，建议创建针对肉毒杆菌神经毒素A的催化结构域的第一组纳米抗体，肉毒杆菌神经毒素A被列为最有效的生物威胁剂之一，同时，被用作神经病学和美容学中的神奇药物。预计这项研究在生物防御和医学领域的更广泛/商业影响。 我们的系统将允许在大肠杆菌中生产的纳米抗体的快速和廉价的开发。大肠杆菌，并特异性靶向抗原的选择。这种小而稳定的抗原靶向分子的可用性将刺激它们在多种检测和诊断技术中用作抗体的替代品。我们的系统将提供潜在的开发新的方法用于分离，固定和/或灭活的生物活性剂。此外，快速生成具有新特异性的纳米抗体的能力将加快将纳米抗体开发成一类用于治疗感染性和非感染性疾病的新型药物的努力。

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.