Gene Therapy for Restenosis

Getting Nearer the Heart of the Matter

From the Krannert Institute of Cardiology (S.B., K.L.M.), Indiana University School of Medicine, and the Richard L. Roudebush Veterans Administration Medical Center (K.L.M.), Indianapolis, Ind.

Correspondence to Keith L. March, MD, PhD, FACC, Krannert Institute of Cardiology, 1111 West 10th St, Indianapolis, IN 46202. E-mail march{at}kimail.dmed.iupui.edu

Abstract—Intensive work over the past decade has been directed to the study of vascular gene transfer as an approach to the unresolved problem of restenosis. This effort has resulted in a significant foundation of knowledge relative to the activities of potentially therapeutic gene products as well as the capabilities and limitations of vector systems and mechanical delivery modalities available for effecting the vascular expression of these gene products. In several instances, significant progress has been made by experiments highlighting unexpected difficulties and the need for more comprehensive understanding. It is thus now possible to clearly define and address specific challenges that must be overcome in order to make feasible progress from the preclinical to the clinical arena. The key challenges at present appear to include the evolution of clinically practical delivery methods that meet the kinetic requirements of achieving efficient gene transduction and the availability of vectors that maximize efficiency while minimizing undesirable host responses. Emerging data suggest that approaches to solving each of these issues may have recently been developed. Basic research evaluating these new delivery mechanisms and molecular vectors is essential to establish their true potential for use in the clinical arena.

Key Words: gene therapy • restenosis • local delivery • vectors • transduction efficiency

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