Project 444543

As we enter an age where we understand more about genetic disease we are beginning to regularly implement genome sequencing and personalized medicine in clinical practice. These efforts are hampered by a lack of knowledge about how mutations contribute to disease. This is particularly the case for diseases like Niemann Pick disease type C (NPC), a rare genetic disease in which most patients present with a mutation that has not previously been reported. This leads to long wait times between presentation and definitive diagnosis, as specialized laboratories are required to biochemically diagnose each potential patient. Here, we propose a new method to quickly and easily create every possible mutation in each DNA base in the NPC1 gene using next-generation gene editing technologies. Once we have generated a group of these mutant cells, we will perform a functional test to rapidly ascertain if each would likely lead to developing Niemann Pick or not. Once identifying which mutations are disease-causing, we plan to test various drugs that are currently in clinical or preclinical trials for NPC to further classify a mutation into categories based on drug-response.