SBIR Phase I: Nuclease-Shielded DNA Aptamer Antibiotics that Couple with Complement

这个小型企业创新研究(SBIR)第一阶段的项目是设计DNA适体，它将与C1qr共价连接，随后将诱导对目标生物体的免疫反应。具体地说，这项第一阶段的工作有以下几个关键目标：1)利用2‘-氟或其他化学修饰来重建针对分离的表面抗原的适体，以获得更好的特异性，使适体具有核酸酶抗性；2)对成功的适体进行克隆和测序；3)设计更适合于将来在体内应用的新的适体-C1qRs结合化学；4)通过透射电子显微镜和其他技术来验证其作用机制。这项拟议的技术可能会对对抗原本难以治疗的抗药性细菌和寄生虫病产生非常深远的积极影响。随着时间的推移，可以形成新的适体家族，并与体内的补体系统结合，以对抗由于机体突变而出现的疾病和患者的复发。

This Small Business Innovation Research (SBIR) Phase I project is to design DNA-aptamers that will be covalently linked to C1qrs and will subsequently induce an immune response to the target organism. Specifically, this Phase I work has the following key objectives: 1) recreating the aptamers against isolated surface antigens for better specificity with 2'-fluorine or other chemical modifications to make the aptamers nuclease-resistant, 2) cloning and sequencing the successful aptamers, 3) devising new aptamer-C1qrs conjugation chemistry that would be more amenable to future in vivo applications, and 4) verifying the mechanism by transmission electron microscopy and other techniques.The commercial application of this project is in the area of infectious diseases. The proposed technology could have a very far-reaching, positive impact on combating otherwise antibiotic-resistant bacteria and parasitic diseases that are difficult to treat. New families of aptamers could be made over time and coupled to the complement system in vivo to combat emerging diseases and patient relapses due to organism mutations.