SENDAI VIROSOMAL INFUSION OF AN ADENOASSOCIATED VIRUS-DERIVED CONSTRUCT CONTAINING NEUROPEPTIDE-Y INTO PRIMARY RAT-BRAIN CULTURES

A novel neuronal gene-delivery system was investigated in primary neur on-enriched cultures with respect to driving the expression of neurope ptide Y (NPY). This delivery system consists of an adeno-associated vi rus-derived (AAV) plasmid, pJDT95npy, encapsulated in reconstituted Se ndai virosomes, pJDT95npy contains full length rat NPY cDNA inserted d ownstream from the P40 promoter in a cap-gene deleted AAV-derived cons truct. The rep-sequences under control of the P5 and P19 promoters are intact. Virosomally encapsulated pJDT95npy drove the expression of NP Y mRNAs, predominantly by P40. Total cellular NPY immunoreactivity and release in the presence of depolarization increased following pJDT95n py-transfection. Neither empty virosomes nor virosomes containing pJDT 95 affected NPY mRNA expression or immunoreactivity. This study demons trates that an AAV-derived plasmid can drive exogenous gene expression in intact neurons after infusion by Sendai virosomes.