Gene transfer by adeno-associated virus vectors into the central nervous system

Adeno-associated virus (AAV) vectors are derived from a nonpathogenic and defective human parvovirus. Although currently unable to display the integration specificity featured by its wild-type parent, the recombinant AAV (rAAV) system has continued to attract enormous interest primarily due to its unique features such as safety, high titers, broad host range, transduction of quiescent cells, and vector integration. Recently, rAAV-mediated in vivo gene transfers have demonstrated efficient long-term transduction (from 3 months to more than 1.5 years) and lack of cytotoxicity and cellular immune responses in the target tissues, especially in the CNS. Alternative approaches using rAAV plasmid DNA in nonviral gene delivery systems also generated promising results. Propelled by various efforts to improve the system, rAAV vectors will provide numerous opportunities to explore the potential therapeutic applications in humans.