Aptamer Reagents for Immunologic Analysis of Underrepresentative Mammalian Models of Tuberculosis

该计划的目标是解决在非哺乳动物模型和免疫试剂有限的哺乳动物模型（如豚鼠、雪貂、棉鼠）中用于鉴定和区分免疫细胞和表征免疫反应的试剂（抗体、蛋白质、配体）的有限可用性。例如，豚鼠感染结核分枝杆菌后的疾病进展表现出人类结核病的许多特征。虽然该模型作为一种理解和描述疾病机制的研究工具已经使用了100多年，但免疫分析受到豚鼠特异性免疫试剂有限可用性的限制。另一个例子是雪貂模型，免疫研究也因缺乏免疫试剂而受到限制。在该项目中，Base Pair Biotechnologies将利用其专利技术进行高复用适体选择，在第一阶段快速生成至少60种针对豚鼠和雪貂重要免疫标记物的新亲和试剂。我们在结核病动物模型方面的专家顾问将与我们具有丰富生物信息学经验的工作人员一起帮助选择目标。这些新试剂将被表征为它们的结合常数，特异性，并在elisa样测定和ELISpot中证明。在第二阶段，我们将使用相同的工艺生产至少100种以上的试剂，并将其用于与癌症免疫学研究和临床试验相关的其他应用。

This goal of this program is to address the limited availability of reagents (antibodies, proteins, ligands) for the identification and discrimination of immune cells and the characterization of immune responses in nonmammalian models and mammalian models for which immunologic reagents are limited (e.g. guinea pig, ferret, cotton rat). For example, the progression of disease that follows infection of guinea pigs with Mycobacterium tuberculosis displays many features of human TB. While this model has been used for more than 100 years as a research tool to understand and describe disease mechanisms, immunologic analyses are constrained by the limited availability of immunological reagents specific for the guinea pig. Another example is the ferret model where immunologic studies also have been limited by the lack of immunological reagents. In this project, Base Pair Biotechnologies will use its patented process for highly multiplexed aptamer selection to rapidly generate at least 60 new affinity reagents in Phase I to important immune markers in guinea pigs and ferrets. Our expert consultant in TB animal models will aid in target selection along with our staff with extensive bioinformatics experience. These new reagents will be characterized for their binding constants, specificity, and demonstrated in ELISA-like assays, and ELISpot. In Phase II, we will use the same process to generate at least 100 more reagents and employed in additional applications relevant to cancer immunology studies and clinical trials.