Kobe Outtier

My name is Kobe Outtier. I earned my Master’s degree in Biomedical Sciences at Ghent University, Belgium. During my time in Ghent, I focused my research internship and master’s dissertation on optimizing prime editing for efficient generation of brca2 knock-in variants in zebrafish. This experience not only enriched my research and soft skills, but also motivated me to pursue doctoral research.
My true passion lies within the field of human genetics. For many years, I have been particularly inspired by the breakthroughs in gene editing and its applications in gene therapy, specifically for inherited retinal disorders (IRDs). Therefore, when I learned about the ProgRET consortium, I was eager to join. I am immensely grateful for the opportunity to contribute to the development of innovative therapies for IRDs, specifically focussing on the CRX gene. I look forward to applying my expertise in gene editing within this research field.

I am confident that this experience will further enhance my skills and knowledge, enabling me to make meaningful contributions to the field of gene therapy. Looking ahead, I am committed to enhancing our understanding and treatment of IRDs through international collaboration and innovative research. I believe with the ProgRET consortium, we can achieve significant advancements in managing these diseases, ultimately advancing patient outcomes.

Evaluating allele-specific invalidation therapies for autosomal dominant CRX mutations

Carriers of dominant CRX pathogenic missense variants can present with different clinical phenotypes: Leber Congenital Amaurosis (LCA), cone-rod dystrophy (CRD) and retinitis pigmentosa (RP). Moreover, individuals with pathogenic variants can be asymptomatic (non-penetrance). Based on preliminary data, we hypothesise that this may be due to aberrant splicing even in the case of missense variants not localized at canonical splice sites. To test this hypothesis, the PhD student (DC10) will develop a CRX minigene assay to investigate the effect on splicing of selected CRX missense variants. In parallel, DC10 will validate splicing effects in iPSC-derived retinal organoids from asymptomatic and symptomatic patients within the same family. Furthermore, DC10 will assay the effect of mutant allele-specific knockdown using CRISPR-Cas9-mediated genome editing and/or ASO-mediated exon skipping to further validate these results and as a potential therapeutic strategy. The work performed by DC10 could provide a prognostic tool for testing the pathogenicity of CRX variants and lead to the development of innovative therapeutics.