Controlled integration of exogenous DNA within the genome has obvious advantages in gene therapy and could circumvent the dangers associated with random genomic integration. In an Advanced Online Publication in Nature Biotechnology, Eric Olivares and colleagues describe the use of a bacterophage ΦC31 integrase to achieve site-specific integration of therapeutic genes (Nature Biotechnology, doi:10.1038/nbt753, 15 October 2002).

The integrase directs recombination between the phage attP site and the host attB site. Olivares et al. tested whether this system could be exploited to deliver therapeutic human genes such as alpha1-antitrypsin (hAAT) or Factor IX (hFIX). The integrase functioned effectively to augment hAAT and hFIX expression in murine livers. The levels persisted after partial hepatectomy suggesting the hFIX had integrated into the genome in liver cells. They confirmed integration and identified two genomic sequences that resemble the attP site and serve as specific integration sites.