Testing the efficacy of new NF1 gene therapy candidates in human cell types

While intervention approaches range from NF1 gene replacement to targeting a genetic factor in the Ras signaling pathway are promising, there is currently no humanized model to develop an efficient in vivo transduction. In this proposal, we will develop a new gene therapy platform with NF1-depleted human Schwann cells, neurons, and cardiomyocytes, for a new NF1 gene replacement candidate and revealing a genetic ‘Achilles heel’ to neutralize a key signaling, followed by in vivo testing with a humanized mouse model. Our study will provide a humanized pre-clinical model to accelerate current efforts toward curing neurofibromatosis.