Targeting the infectious potential of prions with DNA nanotechnology

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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.