We’ve identified a new adeno-associated virus serotype 9 (AAV9) capsid variant, called adeno-associated virus (AAV) Clone C, which transduces neurofibromas in a mouse model of NF1. Here we propose to rigorously compare transgene delivery and therapeutic efficacy to naïve and neurofibroma-bearing nerves with AAV9 and AAV Clone C encoding reporter and therapeutic neurofibromin transgenes. Efficacy of the AAV vector transgene delivery of neurofibromin will be evaluated in NF1 homozygous knock-out mice crossed to transgenic mice in which Cre recombinase is driven by a Schwann cell precursor promoter (Dhh). We will monitor survival, motor performance, and size and location of neurofibromas in these animals. If the mouse work with AAV-C is successful we will test transduction of Schwann cells in various nerves in non-human primates in an effort to evaluate the translational nature of the capsid’s transduction properties.
Investigators
Casey Maguire, PhD
Massachusetts General Hospital
Xandra Breakefield, PhD
Massachusetts General Hospital
Casey Maguire, PhD
Massachusetts General Hospital
Xandra Breakefield, PhD
Massachusetts General Hospital