Editorial [Hot Topic: Recombinant Adeno-Associated Virus: Current Achievements and Limitations (Guest Editor: Philippe Moullier)]

This special issue was initially meant to help graduate students entering the field of gene therapy by providing a comprehensive review of recombinant adeno-associated virus (rAAV) from virology to current clinical applications. However, each article is of such a high quality that I believe this issue will also provide a useful document for the entire gene therapy community. Although wild type AAV was studied for decades, Xiao Xiao and Jude R. Samulski's paper in 1996 represents the first evidence that rAAV produced efficient and long-term gene transfer in a mouse after a single in situ administration (i.e. the skeletal muscle) [Xiao et al., 1996]. 1996 was also the year of the lentivirus vector [Naldini et al., 1996]. Yet, 1996 was only one year after the Orkin and Motuslky report [Orkin et al., 1995] emphasizing the need for better vectors! Today progress in rAAV-mediated gene transfer is so spectacular that long-term, efficient, and regulatable transgene expression is reproducibly achieved in large animal models. For example, i) the entire limb of hemophilia dogs can be efficiently transduced resulting in long-term phenotypic correction [Arruda et al., 2004]; ii) rAAV administered once in nonhuman primate muscle shows sustained regulatable transgene expression for more than 6 years [Rivera et al., 2005]. Simultaneously, the discovery of new AAV serotypes along with the ability to encapsidate either “self-complementing” or “single-stranded” vector DNA [McCarty et al., 2001] has turned this vector system into an extremely powerful and versatile tool with preferential organ transduction patterns depending on the AAV capsid origin and/or the vector DNA used. Finally, considerable improvements have been made in the availability of clinical grade rAAV stocks [Snyder et al., 2002], a critical issue, even though large-scale production remains problematic. On behalf of the Current Gene Therapy journal, I would like to thank the authors for their outstanding articles that truly illustrate the impressive number of rAAV-related breakthroughs achieved in the past decade, although with no clear evidence yet that this may be an effective therapeutic approach in humans.