DC3: Development of Antisense Oligonucleotide-Based Therapies for Lysososmal Storage diseases

​

Supervisor: Dr. S. Alves

Host Institute: Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto, Portugal (www.iceta.up.pt)

Secondments planned: Universidad Autónoma de Madrid, Spain; Institut de Recherches Servier, France

Doctoral program: International Doctoral Programme in Molecular and Cellular Biotechnology applied to Health Sciences (Biotec Health) - Porto University

Anticipated starting date: October 1st, 2025

​

Project description:

​

This project aims to develop a novel therapeutic approach for MPS III, a subgroup of lysosomal storage disorders (LSDs), using antisense oligonucleotides (ASOs). LSDs are severe inherited metabolic diseases, often accompanied by neurodegeneration. Despite significant advances in understanding their molecular mechanisms, specific therapeutic options are virtually non-existent. Our team is focusing on RNA-based therapies, particularly ASOs, to address these disorders (consult our projects and works in this link).

This study will focus on the preclinical validation of ASOs for the treatment of MPS III (subtypes A, B, C, and D). The approach targets genes involved in the heparan sulfate biosynthetic pathway, whose accumulation is particularly detrimental in MPS III patients. The goal is to reduce the mRNA levels of these genes, ultimately triggering the decrease of the pathological buildup of heparan sulfate. ASOs will be tested in patient-derived neuronal and hepatocyte lines (iPSC-derived), as well as in an MPS III zebrafish model. Ultimately, this project seeks to validate ASO-based therapies for MPS III and expand treatment options for neglected LSDs.