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Design of therapeutic RNA aptamers imported into mitochodria ot human cells

Abstract : Defects in mitochondrial genome cause neuromuscular diseases, for which no efficient therapy has been developed. Since most mitochondrial mutations are heteroplasmic, wild type and mutated mitochondrial DNA (mtDNA) coexist in the same cell, and the shift in proportion between two mtDNA types could restore mitochondrial functions. The aim of the project was development of carrier-free system for targeting the therapeutic mitochondrially importable RNA into living human cells. During my PhD study, I have synthesized a set of new anti-replicative RNAs containing various chemical modifications, aiming to increase their stability in the cell, and developed a new method for the chemical synthesis of RNA molecules containing cholesterol attached through a biodegradable bridge. Cholesterol containing antireplicative RNAs were characterised by efficient cellular uptake, partial colocalisation with mitochondria and ability to decrease the proportion of mutant mtDNA.
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Submitted on : Tuesday, June 26, 2018 - 3:06:52 PM
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  • HAL Id : tel-01823846, version 1

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Ilya Dovydenko. Design of therapeutic RNA aptamers imported into mitochodria ot human cells. Genomics [q-bio.GN]. Université de Strasbourg, 2015. English. ⟨NNT : 2015STRAJ046⟩. ⟨tel-01823846⟩

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