Associated DC1: Developing cell-targeted delivery of ASOs in skeletal muscle for the treatment of neuromuscular disorders

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Supervisor: Prof. Haiyan Zhou

Host Institute: University College London, UK (www.ucl.ac.uk)

Secondments planned: Universidad Autónoma de Madrid, Spain; AstraZeneca, Sweden

Doctoral program: PhD Program of the University College London

Anticipated starting date: October 1st, 2025

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Project description:

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This project focuses on identifying bioconjugates that can enhance the delivery of ASOs in skeletal muscle, such as to myoblasts or muscle interstitial fibroblasts, to improve the biodistribution and in vivo efficacy of ASOs in treating neuromuscular disorders. Following cell surface proteomics and phage display studies that already performed in the host laboratory, we will further optimize the peptide design and validate the uptake efficacy of candidate peptides or bioconjugates in different model systems. These may include 2D cell culture or 3D skeletal muscle culture model and mouse models available in the host lab. In leveraging the expertise of the host laboratory in different ASO strategies development, DC12 will be investigating the therapeutic efficacy of ASO-conjugates in correcting genetic defects in different model systems. These may include exon-skipping or inclusion or gene silencing.