Evaluating a next generation AAV capsid for targeted transduction of Schwann cells

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.