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Targeting the infectious potential of prions with DNA nanotechnology

利用 DNA 纳米技术瞄准朊病毒的感染潜力

基本信息

批准号：
EP/X01729X/1
负责人：
Christopher Serpell
金额：
$ 25.7万
依托单位：
University of Kent
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FX01729X%2F1
关键词：
Targeting infectious potential prions DNA

项目摘要

Amyloids are aggregates of misfolded proteins which are linked to neurodegenerative diseases, and can in some cases be infectious. The mechanistic links between amyloid structure and disease presentation are not yet understood, which means that there is an urgent need for new treatments. Understanding the relationship between their structure and biological role is challenging because it is difficult to isolate populations with single, static structures.We present a new strategy which will enable study of the relationship between amyloid structure/polymerization state and infectivity, by putting DNA nanotechnology to work in controlling amyloid assembly. Using covalent and supramolecular interface of DNA with Sup35NM, an infective yeast amyloid-forming protein, the impact of programmed DNA hybridization upon the amyloid structure, polymorphism, and mechanical properties will be studied, enabling production of stable amyloid assemblies across a range of sizes.The infective potential of the DNA-amyloid materials will then be studied by the expression of [PSI+] phenotype in yeast system which will give us unique and valuable new insights into the structural factors which influence amyloid infectivity, and thus assist in the understanding of neurodegenerative diseases and in production of new therapeutics.

淀粉样蛋白是错误折叠的蛋白质聚集体，与神经退行性疾病有关，在某些情况下可能具有传染性。淀粉样蛋白结构和疾病表现之间的机制联系尚不清楚，这意味着迫切需要新的治疗方法。了解它们的结构和生物学作用之间的关系是具有挑战性的，因为很难分离出具有单一、静态结构的种群。我们提出了一种新的策略，通过将DNA纳米技术应用于控制淀粉样蛋白组装，将使研究淀粉样蛋白结构/聚合状态与感染性之间的关系成为可能。利用DNA与具有感染性的酵母淀粉样蛋白Sup35 NM的共价和超分子界面，将研究程序化DNA杂交对淀粉样蛋白结构、多态性和力学性质的影响，从而能够产生各种大小的稳定的淀粉样蛋白组件。然后，将通过在酵母系统中表达[PSI+]表型来研究DNA-淀粉样蛋白材料的感染潜力，这将使我们对影响淀粉样蛋白感染性的结构因素有独特而有价值的新见解，从而有助于理解神经退行性疾病和生产新的治疗方法。