Herpesvirus saimiri: a potential gene delivery vector (review).
The success of human gene therapy relies on efficient delivery and appropriate expression of therapeutic genes which will cure or slow the progression of a disease. However, current viral vectors do not possess the full complement of properties that are generally believed necessary in an ideal gene delivery system. Therefore, alongside attempts to improve current gene delivery vectors, the identification and evaluation of new viral vectors is crucial to the long-term success of gene therapy. Herpesviruses are large DNA viruses which possess a number of advantages as gene delivery vectors. These relate to an ability to package large DNA insertions and establish lifelong latent infections in which the genomic material exists as a stable episome. This review aims to high-light an alternative herpesvirus vector system based on Herpesvirus saimiri (HVS), and illustrates the properties and development of this potential gene delivery vector. HVS is the prototype gamma-2 herpesvirus, or rhadinovirus, originally isolated from its natural host, the squirrel monkey. HVS is capable of infecting a range of human cell lines with high efficiencies, in particular human carcinoma cell lines. Moreover, the HVS viral genome does not integrate into the cellular genome and persist as a high copy number, circular, non-integrated episome which segregate to progeny upon cell division. This allows the virus to stably transduce a dividing cell population and provide sustained transgene expression for an extended period of time in both in vitro and in vivo studies. These properties merit its continual development as a possible gene delivery vector for the future.
Whitehouse
Adrian
A
School of Biochemistry and Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK. a.whitehouse@leeds.ac.uk
D002277:Carcinoma / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005822:Genetic Vectors; D006567:Herpesvirus 2, Saimiriine; D006801:Humans; D010957:Plasmids; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D019076:Transgenes
C116742:ORF 50 transactivator; D015534:Trans-Activators