Targeting the infectious potential of prions with DNA nanotechnology

淀粉样蛋白是与神经退行性疾病相关的错误折叠蛋白质的聚集体，并且在某些情况下可以是传染性的。淀粉样蛋白结构和疾病表现之间的机制联系尚未被理解，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，因为它是很难孤立的人口与单一的，静态的structure.We提出了一个新的策略，这将使淀粉样蛋白的结构/聚合状态和感染性之间的关系的研究，通过把DNA纳米技术来控制淀粉样蛋白的组装。利用DNA与感染性酵母淀粉样蛋白形成蛋白Sup 35 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、多态性和机械性质的影响，使其能够在一系列大小范围内产生稳定的淀粉样蛋白组装体。然后通过[PSI+]的表达来研究DNA-淀粉样蛋白材料的感染潜力。酵母系统中的表型，这将为我们提供关于影响淀粉样蛋白感染性的结构因素的独特且有价值的新见解，从而有助于了解神经退行性疾病和生产新疗法。

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.