Efficient transduction of human neurons with an adeno-associated virus vector.

An adeno-associated virus vector containing a lacZ gene driven by a CMV immediate-early promoter (AAV beta-gal) was evaluated with respect to its transduction efficiency and integration ability in nondividing human NT neurons. A dose-dependent pattern in transduction efficiency of the AAV beta-gal was demonstrated immunocytochemically, with up to 100% of the neurons expressing the gene product. No neurotoxic effects of the vector were detected. Quantitative PCR analyses of high molecular weight cellular DNA from the transduced neurons indicated that the copy number of the AAV beta-gal genome increased gradually in a time dependent manner, suggesting a slow but progressive rate of vector integration over a period of approximately 1 week following transduction. Equal or greater transduction efficiency of the AAV beta-gal into NT neurons than into a standard target cell line indicated that the NT neurons were readily susceptible to AAV-mediated gene transfer. This study demonstrates that AAV-based vectors can efficiently transduce and stably express a foreign gene in post-mitotic human neurons.