Rational design and targeted selection of DNA-scaffolded nicotine vaccines

描述（由申请人提供）：吸烟导致各种疾病，具有高流动性和高死亡率。然而，戒烟是非常困难的，很大程度上是由于尼古丁依赖。虽然尼古丁疫苗已成为减少尼古丁成瘾的一种可能策略，但现有尼古丁疫苗的效果令人失望，可能是由于它们不能充分诱导尼古丁特异性免疫。在此应用中，我们提出了一种合理设计和构建尼古丁疫苗的新技术。具体来说，我们将探索可编程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方面的专业知识。我们将实施一项三期计划，在疫苗构建和评估之间、免疫原性和效力试验之间交错迭代，并以若干定量基准为指导。我们的目标是在资助期结束前确定1到2个主要候选药物，可能会推进它们向研究新药（IND）提交。可以想象，我们的方法可以扩展到针对任何感兴趣目标的疫苗开发，包括其他滥用药物、传染性病原体和肿瘤抗原，从而为疫苗开发提供新的范例。

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.