¹Mary Crowley Medical Research Center, Dallas, TX, USA

Correspondence: Dr J Nemunaitis, Mary Crowley Medical Research Center, 1717 Main Street, 60th Floor, Dallas, TX 75201, USA. E-mail: jnemunaitis@mcmrc.com

Received 23 September 2005; Revised 19 December 2005; Accepted 8 January 2006; Published online 7 April 2006.

Abstract

Cancer remains a serious threat to human health, causing over 500 000 deaths each year in US alone, exceeded only by heart diseases. Many new technologies are being developed to fight cancer, among which are gene therapies and oncolytic virotherapies. Herpes simplex virus type 1 (HSV-1) is a neurotropic DNA virus with many favorable properties both as a delivery vector for cancer therapeutic genes and as a backbone for oncolytic viruses. Herpes simplex virus type 1 is highly infectious, so HSV-1 vectors are efficient vehicles for the delivery of exogenous genetic materials to cells. The inherent cytotoxicity of this virus, if harnessed and made to be selective by genetic manipulations, makes this virus a good candidate for developing viral oncolytic approach. Furthermore, its large genome size, ability to infect cells with a high degree of efficiency, and the presence of an inherent replication controlling mechanism, the thymidine kinase gene, add to its potential capabilities. This review briefly summarizes the biology of HSV-1, examines various strategies that have been used to genetically modify the virus, and discusses preclinical as well as clinical results of the HSV-1-derived vectors in cancer treatment.