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76 - Herpesviruses as therapeutic agents

from Part VIII - Herpes as therapeutic agents

Published online by Cambridge University Press:  24 December 2009

By
Frank Tufaro  and
James M. Markert
Edited by
Ann Arvin ,
Gabriella Campadelli-Fiume ,
Edward Mocarski ,
Patrick S. Moore ,
Bernard Roizman ,
Richard Whitley  and
Koichi Yamanishi
Frank Tufaro
Affiliation:
Allera Health Products, Inc., 360 Central Avenue, Suite 1560, St. Petersburg, FL 33701, USA
James M. Markert
Affiliation:
University of British Columbia, British Columbia, Canada; Department of Surgery, Brain Tumor Research Laboratories, The University of Alabama at Birmingham, Birmingham, AL, USA
Ann Arvin
Affiliation:
Stanford University, California
Gabriella Campadelli-Fiume
Affiliation:
Università degli Studi, Bologna, Italy
Edward Mocarski
Affiliation:
Emory University, Atlanta
Patrick S. Moore
Affiliation:
University of Pittsburgh
Bernard Roizman
Affiliation:
University of Chicago
Richard Whitley
Affiliation:
University of Alabama, Birmingham
Koichi Yamanishi
Affiliation:
University of Osaka, Japan
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Summary

Introduction

After more than a decade of intensive research and development efforts, the translation of promising viral-based gene therapies from the research lab to the clinic is both promising and unexpectedly challenging. Many of the same properties that make viral vectors attractive candidates to deliver genes for therapeutic purposes also impede the path to successful clinical development.

Vectors for clinical use must be manufactured in relatively high yields such that hundreds of thousands or even millions of “doses” can be generated in a safe and cost-effective manner. Moreover, the resulting vector must exhibit genetic as well as structural stability, withstand storage at various temperatures for up to several years, and cause little or no toxicity in animals, and ultimately in humans.

Herpes simplex viruses (HSV), while widespread in nature, have not been tested in human clinical studies as often as several other commonly used vectors, such as adenovirus, adeno-associated viruses (AAV), and retroviruses. In many ways however, HSV is emerging as a viable therapeutic platform and several clinical studies are either ongoing or planned for the very near future. The reason for this increased focus on HSV is due in part attributable to the unique properties that make HSV a stable and potentially potent vector for controlled gene delivery. In addition, the increasing experience with replication-competent vectors in human clinical studies has made it more familiar with clinicians.

Properties of therapeutic HSV vectors

Therapeutic HSV can be characterized as replication-competent or replication-defective.

Type
Chapter
Information
Human Herpesviruses
Biology, Therapy, and Immunoprophylaxis
 , pp. 1341 - 1352
Publisher: Cambridge University Press
Print publication year: 2007

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