HSV Recombinant Vectors for Gene Therapy



Roberto Manservigi*, Rafaela Argnani, Peggy Marconi
Department of Experimental and Diagnostic Medicine – Section of Microbiology, University of Ferrara, Via Luigi Borsari 46, 44100 Ferrara, Italy


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© Manservigi et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Experimental and Diagnostic Medicine – Section of Microbiology, University of Ferrara, Via Luigi Borsari 46, 44100 Ferrara, Italy; Tel: +39 0532 455401; Fax: +39 0532 247618; E-mail: mns@unife.it


Abstract

The very deep knowledge acquired on the genetics and molecular biology of herpes simplex virus (HSV), has allowed the development of potential replication-competent and replication-defective vectors for several applications in human healthcare. These include delivery and expression of human genes to cells of the nervous systems, selective destruction of cancer cells, prophylaxis against infection with HSV or other infectious diseases, and targeted infection to specific tissues or organs. Replication-defective recombinant vectors are non-toxic gene transfer tools that preserve most of the neurotropic features of wild type HSV-1, particularly the ability to express genes after having established latent infections, and are thus proficient candidates for therapeutic gene transfer settings in neurons. A replication-defective HSV vector for the treatment of pain has recently entered in phase 1 clinical trial. Replication-competent (oncolytic) vectors are becoming a suitable and powerful tool to eradicate brain tumours due to their ability to replicate and spread only within the tumour mass, and have reached phase II/III clinical trials in some cases. The progress in understanding the host immune response induced by the vector is also improving the use of HSV as a vaccine vector against both HSV infection and other pathogens. This review briefly summarizes the obstacle encountered in the delivery of HSV vectors and examines the various strategies developed or proposed to overcome such challenges.

Keywords: HSV, viral vectors, oncolytic vectors, gene therapy, neurodegenerative disorders, cancer, targeting, vaccines..