Maddalena Fuso

I hold a Bachelor’s degree in Biological Sciences and a Master’s degree in Molecular Biology of the Cell. My research experience includes investigating Cas9-induced double-strand breaks in yeast and conducting biochemical studies on CRISPR-associated transposons in bacteria. I am deeply passionate about the potential of genome editing to address present-day challenges in treating genetic diseases and cancer, and in advancing personalized medicine. My goal is to contribute to this field by exploring innovative strategies and pushing the boundaries of what genome editing can achieve.
Beside my academic interests, I enjoy hiking, working out in the gym, and reading fiction, mainly fantasy, and comics, as well as watching movies and tv series. These activities help me to find a balance with my research work.

Allele-specific, mutation-independent rescue of dominant negative acting IRD mutations by single gRNA-Cas variant genome editing

Certain pathogenic variants in known inherited retinal disease related genes are known to cause autosomal dominant disease by gain-of-function pathomechanism. We anticipate to rescue the phenotype by specifically disrupting the aberrant allele via genome editing strategies. Specifically, we will focus on an allele-specific but mutation-independent design to overcome mutational heterogeneity. Within our research group we have identified frequent SNPs in these genes that are also commonly found heterozygous in the general population. The PhD student (DC9) will develop a cell-based reporter assay to unbiasedly screen for potent and specific gRNAs and Cas variants, and will effectively target such SNPs in cis with the respective mutation. DC9 will apply and further develop small and specific synthetic genome editing molecules that will be bioengineered to result in robust mutant allele-specific gene disruption, hereby leaving the wild-type allele of the gene intact. By shutting off the production of mutant protein, the project aims to rescue the disease phenotype in patient-derived cellular models and/or retinal organoids using clinically viable delivery tools (i.e. AAV particles).