7 Adeno-associated Viral Vectors

Abstract

The discipline of gene therapy is relatively young when compared to other fields of study. However, from the start, there has been a clear vision of the expectations required to achieve successful clinical results. These have included (1) efficient transduction of the target cell, (2) long-term expression of the therapeutic gene, (3) lack of immune response to the vector or transduced cell, and (4) absence of toxicity to the patient following delivery. Until recently, this mandate has been met only in part by the numerous viral and nonviral delivery systems. Now, definitive in vivo results meeting all of the above criteria have been established by using the parvovirus adeno-associated virus (AAV) vector system supporting a thorough testing of this vector in the clinical arena. This chapter describes in detail the AAV vector system, production methods, successful in vivo models, and questions related to AAV biology that, when understood, may further enhance the existing vector system.

Research employing AAV as a vector for gene therapy has been driven by the desire to exploit the unique biology and life cycle of this virus. This human parvovirus exhibits many natural features that are absent from alternative vectors. AAV’s most prominent feature, which suits it to applications for long-term gene therapy, is the tendency to establish latent infections through integration into the chromosomal DNA. The fact that AAV lytic cycle generally depends on the presence of a coinfecting helper virus means that, essentially, any uninfected helper cell can potentially serve as a host for...