DC8: Design and Evaluation of Therapeutic Antisense Oligonucleotides (ASOs) for Neurodegenerative Diseases

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Supervisor: Prof. Michela A. Denti

Host Institute: Department CIBIO, University of Trento, Italy (www.cibio.unitn.it)

Secondments planned: Leiden University Medical Center, The Netherlands; Biobizkaia Health Research Institute, Spain

Doctoral program: University of Trento, PhD School in Biomolecular Sciences

Anticipated starting date: July 1st, 2025

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Project description:

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This project focuses on the development and evaluation of antisense oligonucleotides (ASOs) and chimeric U snRNA-based antisense RNAs as splice-switching therapeutical approaches for neurodegenerative diseases. The research will be performed at the Laboratory of RNA Biology and Biotechnology of the Department of Cellular, Computational and Integrative Biology of the University of Trento. Hosted in a Department with state-of-art facilities, the research group has extensive expertise in RNA Therapeutics development and evaluation. The research group has established a High Content screening method for the development of splice-switching ASOs and is employing human iPSC-derived and murine models of neurodegenerative diseases. More information about the Laboratory of RNA Biology and Biotechnology can be found here.

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The project will design ASOs and chimeric U snRNA-based antisense RNAs aiming at regulating splicing of mRNAs involved in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis. High-content screening platforms will be set up and used to screen for the most promising candidates, whose efficiency will then be evaluated in advanced cellular models, including iPSC-derived neurons. The project includes international secondments for additional training and expertise. At Leiden University Medical Center, The Netherlands, the candidate will gain experience in culturing iPSCs and delivering ASOs to the iPSC-derived neurons. At Biobizkaia Health Research Institute, Spain, ASO candidates’ efficiency will be evaluated via in-cell western and digital droplet PCR (ddPCR). An additional secondment will be tailored to the candidate’s specific research needs.