NUT carcinoma (NC) is a highly aggressive malignancy characterized by an oncogenic fusion gene incorporating thegene. To date, no established treatment options exist. CRISPR-Cas9 technology allows precise genomic targeting, thereby presenting a promising therapeutic strategy for cancers with well-defined genomic alterations such as oncogenic fusion genes. In this study, we investigated the effects of CRISPR-Cas9-mediated disruption of thefusion gene in NC cell lines using multiple single guide RNAs (sgRNAs) to target different sites of both fusion partner genes. Our experiments identified promising sgRNA candidates that were shown to successfully disrupt thefusion gene at the DNA level, thus leading to an efficient knockout of the aberrant fusion protein. This genetic disruption resulted in profound functional impairments in NC cells, which included a significant reduction in proliferative capacity, cell-cycle arrest, and induction of apoptosis. These findings underscore the dependency of NC on thefusion gene and highlight the potential of CRISPR-based strategies for targeting cancer at its genetic level. This approach also holds promise for the development of highly specific and effective therapies for many other oncogenic fusion driven cancers. NUTM1BRD4::NUTM1BRD4::NUTM1BRD4::NUTM1
CRISPR Gene Editing