Herpes Simplex Virus/Adeno-Associated Virus Hybrid Vectors for Gene Transfer to Neurons: Preparation and Use

Gene transfer to the central nervous system (CNS) has shown major advances in recent years, with the development of novel vector systems and progress in basic virology (1 –12 ). To improve gene transfer to CNS neurons, we have combined the critical elements of herpes simplex virus-1 (HSV-I) amplicons and recombinant adeno-associated virus (AAV) vectors to construct a hybrid amplicon vector, and then packaged the vector into HS V-1 virions via a helper virus-free system. These HSV/AAV hybrid amplicon vectors have shown efficient transduction and stability of transgene expression in neurons (and other nondividing cell types [13 )], both in culture and after intracerebral injection with no apparent toxicity or immune response, as well as extended transgene expression in dividing cells (14 ). Before detailing the hybrid amplicon vectors, a short description of the two vectors upon which the hybrid amplicon vectors are based is given.