Curiosity and a love for science have guided my journey so far, from a Bachelor’s in Biotechnology at the Polytechnic University of Valencia, including an ERASMUS at the University of Nottingham, to an MSc in Pharmaceutical Sciences at the University of Copenhagen. During my Master’s, I worked at the Finsen Laboratory on drug screening and protein expression, which deepened my interest in translational research. I am now joining the EFFecT network as DC2 at Universidad Autónoma de Madrid under the supervision of Professor Lourdes Desviat, where my research will focus on correcting splicing defects in inherited metabolic diseases using splice-switching antisense oligonucleotides (SS-ASO).

 

Outside the lab, I’m always up for discovering new places, books, and experiences.

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DC2: Correction of splicing defects in inherited metabolic diseases with splice switching ASO (SS-ASO)

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Supervisors: Prof. L.R. Desviat and E. Richard

External mentor: Dr. F. Coppieters

Host Institute: Universidad Autónoma de Madrid, Spain (www.uam.es)

Secondments planned: Astherna, The Netherlands; University College London, UK

Doctoral program: PhD in Biomedical Biosciences of Universidad Autonoma de Madrid

Starting date: September 1st, 2025

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Project description:

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The project focuses on splicing defects (exon skipping, pseudoexon insertion and others) in inherited metabolic disease (IMD) genes expressed in liver and resulting in neurological and/or multisystemic affectation, such as hyperphenylalaninemias (phenylketonuria, PKU) and organic acidemias (propionic acidemia). SS-ASO designed to block aberrant pseudoexon insertion increase transcript and protein levels, both in alleles with pseudoexon activating deep intronic variants and those with hypomorphic variants, thus can be a potential treatment strategy for different patients (doi: 10.1016/j.omtn.2023.102101; 10.1089/nat.2021.0066). In our group (www.cbm.uam.es/lab220), we have also identified vulnerable exons with weak 3’ and/or 5’ splice sites prone to exon skipping with different exonic variants, which are (mis) classified as missense or nonsense. SS-ASO targeting splice silencers may correct the exon skipping defect (doi: 10.1089/nat.2024.0014). In this project, the PhD student will use a combination of methods: bioinformatic analysis, minigenes, RNA affinity studies, CRISPR/Cas and transcript analysis to model and characterize splice defects identified in IMD patients and to identify splice regulatory sequences. In all cases, after the design of SS-ASO to correct  each type of splice defect, testing will be performed in cellular models, edited HepG2 cells, patient’s fibroblasts and/or hepatocyte-like cells derived from edited iPSCs. Transcript and protein analysis, enzymatic activity assays and targeted biochemical readouts will be performed to assess initial efficacy. Optimization based on SS-ASO walk across the target region and use of different chemistries will be performed to obtain a lead candidate SS-ASO for future testing in mouse models. Knowledge of the translatability into the clinic of the in vitro findings will be acquired during secondments.

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