Safety evaluation of gene therapy viral vectors.
Gene therapy has engendered interest in scientists, regulators and the public alike, because it represents the application of current expertise in the areas of cellular and molecular biology to the specific modification of cell function for the purposes of ameliorating disease. As scientific advances broaden the application of gene therapy, it is increasingly important to adequately evaluate the safety of these agents prior to clinical trials. A number of guidance documents have been published which address strategies for preclinical evaluation of gene therapy candidates. Some aspects of preclinical safety evaluation are similar to the development of more traditional drugs, while others are unique, entwined with the molecular and cellular biology needed to accurately describe a gene therapy's activity and distribution. This review provides a summary of some of the practical issues to consider in the preclinical evaluation of gene therapy viral vectors. These range from the demonstrated or theoretical toxicities of a specific vector class, to the risk of inadvertent germline transfer and insertional mutagenesis.
Leibbrandt
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Chiron Corporation, Emeryville, CA 94608, USA. martha_leibbrandt@cc.chiron.com