MOLECULAR BIOLOGY OF THE ADENO-ASSOCIATED VIRUS
Adeno-associated viruses are non-enveloped and non-pathogenic parvoviruses comprising a double-stranded 5.5 kb genome packaged into a capsid assembly of proteins. At less than 50 nm, this virus is one of the smallest used in gene therapy applications. Consequently, its genome is comprised of only two genes, rep and cap encoding for non-structural and structural genes respectively, which are flanked by two 145 bp ITRs (see figure one). The virus is capable of infecting both dividing and non-dividing cells and can only replicate in the presence of a helper virus, (e.g. adenovirus or herpes virus). Uniquely, it can integrate specifically into the mammalian cell genome at position 19q13, a property conferred by its rep protein. Typically, the AAV maintains a latent infection by integrating in this site, and is subsequently mobilised after secondary infection with helper virus. Its ability to mediate long-term expression in the absence of a significant immune response, combined with its lack of pathogenicity, makes this an ideal candidate gene transfer vector.
Diagram One: AAV Genome
