Genevention will help to systematically understand APC stop codon mutation readthrough

Of all genetic mutations causing human disease, approximately 11% are nonsense mutations, also termed premature termination codons (PTCs). In these mutations, a codon that codes for an amino acid is changed into a stop codon, preventing translation of the complete, functional protein. This type of mutation can be found in nearly all known monogenetic diseases including most rare diseases, summing up to 5,000–10,000 diseases or tens of million patients worldwide. It is a viable yet challenging therapeutic strategy to treat these PTCs with translational read­through-inducing drugs (TRIDs). These compounds stimulate the ribosome to interpret the PTC as a sense codon and thereby to restore part of the production of the normal length gene product. TRIDs are important from a clinical point of view, as they may lead to new and improved personalized medicine approaches that will match certain patients in affected genes with more specific drugs.

Together with Dr.Sven Thoms from the University Medical Center Göttingen and Prof. Rina Rosin-Arbesfeld from Tel Aviv University,the project will investigate nonsense mutations in the Adenomatous Polyposis Coli (APC) gene, which is mutated in the vast majority (over 80%) of both hereditary and sporadic colorectal cancers(CRCs). Genevention will develop algorithms to characterize the Stop Codon sequence context of APC mutations and predict which TRIDs will most efficiently restore APC expression to help developing therapeutic approaches. Funding for the project has been acquired in terms of a grant by the German-Israeli Foundation for Scientific Research and Development (GIF I-89-412.20-2017). We are looking forward to this exciting research collaboration and hope to provide useful tools and algorithms to pave the way for individualized Stop codon readthrough therapy!