Development of a next-generation in vivo human gene-editing therapeutic platform - Year two
The over-arching goal of our project is to develop a robust next-generation gene-editing platform to repair the deleterious mutations that are responsible for genetic diseases such as Cystic Fibrosis and cancer. First-generation precision endonuclease technologies have been tremendous for in vitro gene disruption studies and ex vivo treatments, but there has been limited success at developing safe and effective in vivo human gene-editing therapies. To address these issues, we propose to package a highly specific RNA-guided dual nuclease technology (TevCas9), into liposomal delivery vehicles developed by Specific Biologics Inc. (SBI). By combining these technologies, we will create a powerful therapeutic platform that fulfills the target product profile for an ideal in vivo gene-editing platform. As proof-of-principal, we propose to target and repair the CFTR delta F508 mutation, a monogenetic mutation that results in Cystic Fibrosis (CF) and in which >85% of CF patients carry at least one copy of the mutation. CF was chosen as our model due to the high unmet medical needs of these patients and the suitability of SBI’s proposed liposomal (lipid-based) delivery system to target cells of the respiratory mucosa through nebulization. However, following our initial studies TevCas9 will be retargeted to other clinically relevant targets.