EFFICIENT TRANSDUCTION OF GREEN FLUORESCENT PROTEIN IN SPINAL-CORD NEURONS USING ADENOASSOCIATED VIRUS VECTORS CONTAINING CELL-TYPE-SPECIFIC PROMOTERS

In this study, we have evaluated the capacity of recombinant adeno-ass ociated virus (rAAV) vectors, containing cell type-specific promoters, to transduce neurons in vivo in the normal adult rat spinal cord. The neuron-specific enolase (NSE) promoter and the platelet-derived growt h factor (PDGF) B-chain promoter were used to direct expression of a ' humanized' form of the gene for green fluorescent protein (GFP). Neuro n-specific rAAVs were injected into the mid-cervical regions of adult rat spinal cords. At 10-14 days expression was detected in all animals and persisted for up to 15 weeks. Immunocytochemical and morphologica l profiles of transduced cells were consistently neuronal, and there w as no evidence of transgene expression in glial elements. Transduction efficiencies for NSE and PDGF rAAVs were estimated at 15 and 45 infec tious particles per GFP-positive neuron, respectively, in the absence of detectable adenovirus. This study strongly supports a role for rAAV vectors in CNS gene therapy and lays the groundwork for delivery of m ore functional genes to spinal cord neurons as a possible way to enhan ce spinal cord repair following injury.