Expanding Adeno-associated Viral Vector Capacity: A Tale of Two Vectors
Authors: Ghosh, Arkasubhra; Duan, Dongsheng
Source: Biotechnology and Genetic Engineering Reviews, 27 August 2007, vol. 24, no. 1, pp. 165-177(13)
Abstract:Adeno-associated Virus (AAV) is a human parvovirus originally isolated as a contaminant in adenoviral stocks (Atchison, et al., 1965). It is classified as a dependovirus, as opposed to autonomous parvovirus, because it needs a helper virus to complete a productive life cycle (Flotte and Berns, 2005). About 110 serotypes have been identified and they are classifed into seven clades (Gao, et al., 2004). Type-2 AAV (AAV-2) is the first serotype isolated. This is also the most extensively studied prototype AAV. Wild type AAV-2 consists of a 4681nt single-stranded DNA genome and is non-pathogenic (Srivastava, et al., 1983). The ends of the genome are palindromic repeat sequences termed the inverted terminal repeats (ITRs). The AAV genome consists of two open reading frames encoding structural/capsid proteins and replication/regulation proteins, respectively (Figure 1). AAV enters cell through receptor-mediated endocytosis followed by endosomal sorting and trafficking into the nucleus (Ding, et al., 2005). After uncoating, the AAV genome is converted to the double stranded form. In the presence of a helper virus, AAV is reproduced (Berns and Bohenzky, 1987) (Figure 2). Without helper virus, a latent infection cycle is established and AAV is propagated as an integrated provirus (Berns and Linden, 1995). In human cells, AAV-2 specifically integrates in the short arm of chromosome 19 (Kotin, et al., 1990).
Document Type: Research Article
Publication date: August 27, 2007