DC4: Design and Evaluation of Therapeutic Antisense Oligonucleotides (ASOs) for Rare Diseases Affecting Skeletal Muscle

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Supervisor: Prof. Arechavala-Gomeza

Host Institute: Biobizkaia Health Research Institute, Spain (www.bio-bizkaia.eus)

Secondments planned: Radboud University Medical Center, The Netherlands; University College London, UK

Doctoral program: University of the Basque Country (UPV/EHU), Molecular biology and biomedicine doctoral program

Anticipated starting date: September 1st, 2025

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Project description:

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This project focuses on the development and evaluation of innovative therapeutic antisense oligonucleotides (ASOs) for rare neuromuscular disorders with skeletal muscle involvement. Hosted by the Nucleic Acid Therapeutics for Rare Diseases Group at Biobizkaia, a team with extensive expertise in ASO development and therapeutic evaluation, this research builds on robust in vitro platforms established in the lab. These platforms, based on in-cell western and digital droplet PCR (ddPCR), are used to assess therapies for Duchenne muscular dystrophy (DMD), myotonic dystrophy type 1 (DM1), and collagen VI-related disorders (COL6 RD). More information about the group can be found here.

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The project will design ASOs targeting specific patient mutations and screen the most promising candidates in advanced cellular models, including primary muscle cell cultures, iPSC-derived myoblasts, and fibroblasts. It will also address a critical challenge: improving the delivery efficiency of ASOs to skeletal muscle. The project includes international secondments for additional training and expertise. At Radboud University Medical Center (RUMC), the candidate will gain experience in culturing iPSCs and generating CRISPR/Cas9-edited iPSC lines. At UCL, ASO candidates will be evaluated in animal models to assess their therapeutic potential. An additional secondment will be tailored to the candidate’s specific research needs.