Rational design and targeted selection of DNA-scaffolded nicotine vaccines

描述（由申请人提供）：吸烟导致各种类型的疾病，具有高流动性和死亡率。然而，戒烟是非常困难的，主要是由于尼古丁依赖。虽然尼古丁疫苗已经成为减少尼古丁成瘾的可能策略，但现有尼古丁疫苗的功效一直令人失望，这可能归因于它们对尼古丁特异性免疫的诱导不足。在本申请中，我们提出开发一种新的技术来合理设计和构建尼古丁疫苗。具体来说，我们将探索可编程的DNA纳米结构来组装尼古丁和其他免疫原性成分，以增强疫苗的免疫原性和有效性。为了实现这一目标，我们将结合联合收割机的专业知识，从免疫学，有机和DNA结构化学，生物信息学，以及尼古丁成瘾和行为的药理学。我们将实施一个三阶段计划，疫苗建设和评估之间，免疫原性和有效性测试之间是交错和迭代的，并以几个量化基准为指导。我们的目标是在资助期结束前确定1至2个主要候选药物，可能会将其推进到研究性新药（IND）提交。可以想象，我们的方法可以扩展到针对任何目标的疫苗开发，包括其他滥用药物，感染因子和肿瘤抗原，从而提供疫苗开发的新范式。

DESCRIPTION (provided by applicant): Cigarette smoking causes various types of diseases with a high mobility and mortality. Yet, it is very difficult to quit smoking, largely due to nicotne dependence. Although nicotine vaccines have emerged as a possible strategy to reduce nicotine addiction the efficacy of existing nicotine vaccines has been disappointing, possibly attributed to their insufficient induction of nicotine-specific immunity. In this application, we propose to develop a new technology to rationally design and construct nicotine vaccines. Specifically, we will explore programmable DNA-nanostructures to assemble nicotine and other immunogenic components to enhance the immunogenicity and efficacy of the vaccines. To accomplish this, we will combine expertise from immunology, organic and DNA-structural chemistry, bioinformatics, and the pharmacology of nicotine addiction and behaviors. We will implement a three- phase plan, which is staggered and iterative between vaccine construction and assessment, and between immunogenicity and efficacy tests, as well as being guided by several quantitative benchmarks. Our objective is to identify 1 to 2 lead candidates by the end of the funding period, possibly advancing them towards an Investigational New Drug (IND) submission. It is conceivable that our approach can be expanded to the development of vaccines against any target of interest, including other drugs of abuse, infectious agents, and tumor antigens, thus providing a new paradigm in vaccine development.