Need of a site-specific integrating vector in gene therapy has become pressing, as recent work has shown that many of the current integrating vectors used preferentially integrate in the vicinity of genes. A site-specific integrating vector would reduce the risk of insertional mutagenesis posed by randomly integrating vectors, and a non-viral vector would reduce the safety and immunogenicity problems associated with viral vectors. The phiC31 integrase is a protein from Streptomyces phage phiC31 that has been developed as a non-viral site-specific gene therapy vector. The phiC31 integrase catalyzes the integration of a plasmid containing attB into pseudo attP sites in mammalian genomes. It has been shown to function in tissue culture cells as well as in mice. Vectors based on the phiC31 integrase were able to treat tyrosinemia type I in a mouse model and two forms of epidermolysis bullosa in keratinocytes from patients, demonstrating its effectiveness as a gene therapy vector. Development of phiC31 integrase-based vectors is still underway, but it has already been shown to provide long-term expression through site-specific integration.