DC5: Characterization of ASO-intracellular protein partners to increase ASO therapeutic index

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Supervisor: Dr. A. Goyenvalle

Host Institute: Université de Versailles Saint-Quentin-en-Yvelines, France (www.uvsq.fr)

Secondments planned: Radboud University Medical Center, The Netherlands; Leiden University Medical Center, The Netherlands

Doctoral program: Doctoral program Life Sciences and Health of Université Paris-Saclay

Anticipated starting date: October 1st, 2025

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Project description:

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This project aims at studying one of the main bottlenecks of ASO-based therapeutics by identifying ASO-protein partners which could significantly increase ASO potency. In this context and following a proteomic and functional screen already performed in the host laboratory, we propose to determine and subsequently validate the proteins promoting and inhibiting the ASO uptake and trafficking to their RNA-targets. Considering the expertise of the host laboratory in neuromuscular diseases, DC5 will be working on exon skipping therapies for Duchenne muscular dystrophy, using both in vitro and in vivo models of the disease. Identified proteins/genes will be specifically downregulated in vitro in muscle cells and the most promising candidates impacting the effect of ASO will be evaluated in vivo in DMD mouse models.