Viral vectors, tools for gene transfer in the nervous system

Viral vectors are becoming increasingly important tools to investigate the function of neural proteins and to explore the feasibility of gene therapy to treat diseases of the nervous system. This gene transfer technology is based on the use of a virus as a gene delivery vehicle. In contrast to functional analysis of gene products in transgenic mouse, viral vectors can be applied to transfer genes to somatic, post-mitotic cells of fully developed animals. To date, five viral vector systems are available for gene transfer in the nervous system. These include recombinant and defective herpes viral vectors, adenoviral vectors, adeno-associated viral vectors and lentiviral vectors. Of these vectors herpes and adenoviral vectors are the most common in use. To date, one of the main hurdles in applying these two vector systems is the focal immune response that occurs following intraparenchymal infusion. Despite this limitation, herpes and adenoviral vectors have been used successfully to modify the physiological response to injury in several rodent models of neurodegeneration. The first purpose of this review is to describe the principles of the generation of viral vectors and to discuss the advantages and disadvantages of the viral vector systems currently in use for gene transfer in the nervous system. Secondly, we give an overview of the performance of these vectors following direct infusion in the nervous system and review the results obtained with these vectors in animal models of neurodegeneration and regeneration. The results of these initial studies have provided a framework for future experiments based on gene transfer strategies with viral vectors to study normal physiology and pathology of the nervous system.