The winning team of the CRACK IT Challenge InMutaGene led by GeneWerk, has created a website to showcase the assay they are developing to improve the safety of novel gene therapy products without using animals.
Gene therapy (GT) is emerging as a medical reality for the treatment of inherited and acquired disorders. Generally the therapeutic DNA sequence is delivered via a vector system, with some vectors integrating permanently into the genome. Insertional mutagenesis leading to oncogenesis is a recognised GT safety concern. Preclinically, GT safety is mainly assessed through in vivo rodent or non-rodent (dog or non-human primate) studies, which are costly, time consuming and not always predictive of the effect in humans.
The team is developing a standardised assay for Individualised Genotoxicity testing (InGeTox) to assess vector safety using patient-derived human induced pluripotent stem cells differentiated into hepatocytes. Using patient cells (incorporating the individuals genetic and disease background) allows the risk for vector associated genotoxicity to be assessed in an individual undergoing a specific gene therapy treatment. The assay thereby provides personalised safety assessment of each disease targeted gene therapy.