DC1: Development of antisense technology-based strategies for neurometabolic diseases

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Supervisor: Dr. A. Garanto 

Host Institute: Radboud University Medical Center, The Netherlands (www.radboudumc.nl)

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

Doctoral program: PhD program of the Radboud University

Anticipated starting date: September 1st, 2025

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Project description:

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Inherited metabolic diseases (IMD) are one of the most significant causes of death in infants and therefore there is an unmet need to further develop therapeutic strategies for these diseases. DC1 will work on the development of an innovative mutation-independent strategy based on antisense technology (single and double stranded antisense molecules) to target the liver and boost gene expression of metabolic genes to restore the biochemical pathway. The designed molecules will be tested in several cellular models (HEK293T, patient and control fibroblasts and iPSC-derived hepatocytes). Once efficacious molecules have been identified, further optimization using chemical modifications will be performed and the metabolic and genetic safety will be tested by untargeted metabolomics and transcriptomics (e.g., possible altered metabolic pathways and off-targets, resulting from the delivery of these molecules, respectively).

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