Optimized AAV vectors for therapeutic Schwann cell targeting in NF1

There is an urgent need to identify new treatments to prevent or shrink PNs. Targeted gene therapies that use viruses to restore the function of neurofibromin in SCs may be beneficial for PN. However, the DNA sequence that codes for neurofibromin is too large to fit in AAV gene therapy vectors. In this project, our research team at Cincinnati Children’s Hospital and California Institute of Technology will overcome these challenges to create new gene therapies to treat PN in NF1 by 1) developing better AAVs that can infect SCs and 2) identifying virus-compatible proteins that shrink or prevent PNs when expressed in SCs with AAV. We will test these gene therapies in genetically engineered mouse models of PN, which will serve as an important first step in bringing AAV gene therapies for NF1 to the clinic.