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种系统，该系统在成本低廉、使用简单的同时，能够在体外产生针对感兴趣抗原的重链骆驼抗体(也称为VHH，或纳米体)的可变域。该系统将不需要骆驼疫苗接种，并将使用通用预制库来快速分离具有所需特异性的纳米体。为了证明这一概念，有人提议创建第一组针对肉毒杆菌神经毒素A催化区域的纳米体，肉毒杆菌神经毒素A被列为最有效的生物治疗药物之一，同时被用作神经学和美容领域的奇迹药物。这项研究有望在生物防御和医学领域产生更广泛的商业影响。我们的系统将允许快速和廉价地开发在大肠杆菌中生产的纳米体，并专门针对所选的抗原。这种小而稳定的抗原靶向分子的出现将刺激它们在多种检测和诊断技术中作为抗体的替代品。我们的系统将为开发分离、固定化和/或灭活生物活性物质的新方法提供潜力。此外，快速产生具有新特异性的纳米体的能力将加快努力，将纳米体开发成治疗传染病和非传染性疾病的新型药物。

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.