The use of DNA viruses as vectors for gene therapy

The need for efficient transfer of potentially therapeutic genes to defined cell populations has stimulated the development of vectors based on viruses. To date, most effort has been spent on the RNA-containing retroviruses. These viruses, however, possess a number of disadvantages including an inability to infect nondividing cells as well as having potential for oncogenicity and insertional mutagenesis of host cell genes due to random chromosomal integration. These disadvantages have led to the development of vectors based on DNA-containing viruses such as adenovirus, herpes simplex virus and parvovirus. These viruses possess a number of attributes favourable to their use in gene therapy. Adenoviruses, for example, were first considered as potential vectors for the genetic treatment of lung conditions due to their natural affinity for respiratory epithelium. However, other features including their ability to be prepared at high titres, to direct high levels of foreign gene expression and their extrachromosomal existence has resulted in their development for the treatment of numerous other diseases. In many studies, adenovirus vectors have been shown to efficiently infect target cell populations and to express proteins at therapeutic levels in the absence of significant toxicity. The ability of herpes simplex virus to reside in neurons in a latent state that does not appear to affect normal cellular physiology has sparked interest in this virus as a potential vector in the treatment of neurological disorders. A subgroup of parvoviruses, namely the adeno-associated viruses, have a prediliction for integration at a defined chromosomal location and may represent a safer alternative to retroviruses.