Subpial AAV Delivery for Spinal Parenchymal Gene Regulation in Adult Mammals.

ABSTRACT

The use of adeno-associated virus (AAV) vectors has become an attractive method for treatment of a variety of neurodegenerative disorders by permitting targeted gene upregulation or silencing in the CNS. Systemic and intrathecal infusion, while preferable routes of vector delivery, have shown encouraging but variable efficacy due to the poor permeability of AAV into spinal cord and brain parenchyma in adult mammals. Recently we have developed a novel and relatively noninvasive technique of spinal subpial vector delivery. This technique confers widespread transgene expression throughout the spinal parenchyma, including both white and gray matter. We have demonstrated that this technique can be performed safely, with a high level of accuracy, and is effective in both small (mouse or rat) and large preclinical (adult pig or nonhuman primate) animal models. In this chapter we provide a comprehensive description of the subpial vector delivery technique in adult rodents (mouse and rat) and large preclinical animals (adult pig and nonhuman primates).