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(Circulation Research. 2000;86:923.)
© 2000 American Heart Association, Inc.

MiniReviews

Human Gene Therapy

The Good, the Bad, and the Ugly

Jeffrey M. Leiden

From the Harvard School of Public Health and Harvard Medical School, Boston, Mass.

Correspondence to Jeffrey M. Leiden, Harvard School of Public Health, Laboratory of Cardiovascular Biology, Bldg II, Room 117, 677 Huntington Ave, Boston, MA 02115. E-mail leiden@cvlab.harvard.edu

Key Words: gene therapy • catheters • adenovirus • biocompatibility

	Introduction

 
During the last several years, we have witnessed "the best of times and the worst of times" in the embryonic field of gene therapy. Rapid advances in human genomic sciences, the development of novel mouse models of human diseases, and the construction and characterization of new vector systems for in vivo gene transduction have significantly expanded the potential feasibility of human gene therapy. On the other hand, the tragic events surrounding the gene therapy–related death of Jessie Gelsinger and subsequent revelations about additional unreported gene therapy–related complications have seriously damaged both the scientific credibility and public confidence in gene therapy. Given these recent events, this would seem to be an opportune time to pause and carefully reassess where we are and, more importantly, where we should be going in this promising but controversial field.

Toward this end, I would like to consider 3 distinct but related questions. First, does the currently available scientific evidence support the feasibility of human gene therapy? If so, what types of preclinical data are necessary to justify human clinical experimentation? Second, what can be learned from our recent experiences about the design of future human gene therapy trials? And, third, what safeguards are necessary to ensure the objectivity of investigators in the field and to thereby inspire the required level of confidence on the part of patients and their families, the scientific community at large, and the general public?

	The Science: Genes, Vectors, and Devices

 
Most successful gene therapy approaches require the combination of an efficacious therapeutic gene, an appropriate vector . . . [Full Text of this Article]

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