9 Emerging Viral Vectors

Abstract

Gene therapy is already in clinical use with a number of viral and nonviral vector systems (Marcel and Grausz 1997). Nevertheless, there are a number of perceived and proven issues with some of these systems (e.g., the immunogenicity and toxicity of some versions of adenoviral vectors [Dodge 1995; Knowles et al. 1995], and the insertional activation/inactivation of retrovirus vectors [Temin 1990]). Although some of these issues may be the normal obstacles encountered in trying to develop new human therapies, one response to them has been the active investigation in a number of laboratories and clinical situations of alternative delivery systems. Vector systems are now being developed from additional viruses, based in part on their desirable properties or avoidance of particular safety issues.

The reasons for examining one vector system in particular vary, but they usually fall into the following classes:The system has a particularly attractive property (e.g., very high levels of transgene expression over a limited period of time for alphavirus vectors).

The system has a format for which there is extensive clinical experience (e.g., vaccinia vectors).

The system seems simple or easy to develop in order to make clinical material in large quantities (e.g., baculovirus or other vectors, such as Avipox, that replicate in nonhuman cells but abortively infect human cells).

There is extensive understanding of the viral life cycle and molecular virology (e.g., simian virus 40, herpes simplex virus, and alphavirus).

Many systems combine some of these properties, and in fact a number...