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Work from StarT fellows Melita Kaltak (ESR10) and Zelia Corradi (ESR5) is published in Human Molecular Genetics. The manuscript reveals that missense and synonymous variants in ABCA4 play a major role in pre-mRNA splicing. This study refines the classification of ABCA4 variants, leading to a more accurate prediction of disease progression and selection of therapeutic strategies targeting Stargardt disease.
Latest research paper of ESR9, Nuria Suárez Herrera: In this research, we present a proof-of-concept approach to address the high allelic heterogeneity in ABCA4, which is a great challenge in designing therapies for STGD1. This strategy is based on delivering several antisense oligonucleotides embedded in U7snRNAs, providing the opportunity to target various splicing defects using a single therapeutic vector. The multiple antisense oligonucleotide delivery approach showed potential to rescue several splicing defects, and offers the possibility to target a larger group of STGD1 patients. However, the journey does not end here – more research is crucial to overcome the encountered challenges. 
ESR12, Pietro De Angeli: Wrapped up our latest manuscript showcasing the potential of advanced cellular models (#iPSC -differentiated photoreceptor precursors) in unravelling splicing defects, with a touch of gene editing magic to rescue them. 
In the latest collaborative publication (De Baere lab, Martínez Morales lab & Tena lab) with StarT fellows Víctor López Soriano (ESR3), Soraya Kalayanamontri (ESR2) and Alfredo Dueñas Rey (ESR7) is shown that through extensive comparative 3D genome mapping, based on genome-wide (Hi-C), promoter-centric (HiChIP) and locus-specific (UMI-4C) assays of human neural retina and RPE, that gene regulation at key loci for inherited retinal disease (IRD) is likely mediated by tissue-specific chromatin interactions. A comparative 3D genome analysis between neural retina and RPE/choroid revealed that almost 60% of 290 known IRD genes were marked by differential 3D genome structure and/or cis-regulatory interactions! One of these genes is ABCA4, which is implicated in the most common autosomal recessive IRD.  Our Partner Organisation Fighting Blindness Ireland announced the publication of a collaborative study in the scientific journal Nature Scientific Reports. They found a gene variant enriched in Irish Stargardt disease patients. Stargardt Disease is a rare inherited retinal degeneration; the number of affected people is estimated to be 1 in-10,000, however the exact amount is difficult to calculate due to the high level of clinical variation in the population. The study is aiming to help both doctors and geneticists give a more accurate diagnosis and therefore is paving the way for better access to the correct therapy needed in each case.
Thank you to everyone who worked on this study, amongst them the StarT fellows Iris Post (ESR13) and Zelia Corradi (ESR5). On Thursday, November 3, 2022 our 14 ESR fellows from the StarT network presented the outputs from their PhD studies. Additionally, three renowned keynote speakers covered ‘IRD omics towards better diagnosis’ (Rando Allikmets), ‘Mechanisms of Inherited Retinal Diseases’ (Mariya Moosajee) and ‘New Therapies for IRD’ (Alessandra Recchia). StarT welcomed 50 on-site participants in the Radisson Blu Hotel, Dublin. Via the hybrid event platform provided by Crowdcomms and streaming via the YouTube channel of Fighting Blindness, another 250 participants attended this really great Final conference providing a forum for the many significant outputs from the ESR fellows to be presented and discussed  Three StarT ESRs, Munevver Burcu Cicekdal (ESR3), Víctor López Soriano (ESR3) and Alfredo Dueñas Rey (ESR7), took part in amazing work investigating a multi-omics approach to explore the regulatory landscapes implicated in North Carolina macular dystrophy! The work can be found here.  |
