Prospects for adenovirus-mediated gene therapy of inherited diseases of the myocardium.

Abstract

Time for primary review 30 days. Many genetic loci linked to a variety of diseases have been identified, and disease-causing mutations characterized. These have included diseases of the myocardium, such as X-linked dilated cardiomyopathy [1–3], hypertrophic cardiomyopathy [4–6], and Long QT syndrome [7–9]. The elucidation of gene defects has allowed different therapeutic strategies to be proposed, including the use of pharmaceutical agents to replace or to antagonize the mutated protein, and replacement of the defective gene with a functional one (gene therapy). There have been many publications describing the use of vectors to transduce target cells for the correction of gene defects or for anti-viral therapy (for reviews see [10–14]). Such vectors have included recombinant retroviruses, adenoviruses, adeno-associated viruses, and herpes viruses, as well as non-viral vectors. Each vector has inherent advantages and disadvantages. At this time the adenoviruses are most commonly used and represent the most likely vector for efficient transduction of the myocardium. While many groups have reported the use of recombinant adenoviruses to transduce cells in vitro and in vivo, and even their use in clinical trials for the correction of the cystic fibrosis gene defect [15, 16], there have been few reports describing the targeted expression of gene products for the correction of myocardial diseases. In this review we will discuss the potential of gene therapeutic approaches for the treatment of myocardial disease, as well as consider some of the limitations and risks associated with the use of the adenovirus-based vectors. Recombinant adenoviruses have been the most commonly utilized vectors for the transduction of cells both in vitro and in vivo. This has primarily been due to their ability to be propagated and purified to high titers, their ability to transduce non-dividing cells, and their broad spectrum of target tissues. Most studies … * Corresponding author. Pediatric Cardiology, Baylor College of Medicine, One Baylor Plaza, Room 333E, Houston TX 77030, USA. Tel.: +1 713 7987342; Fax: +1 713 7988085; E-mail: jtowbin@bcm.tmc.edu