Gene Therapy in Orthopaedic Surgery
David Hannallah, MD, MSc; Brett Peterson, MD; Jay R. Lieberman, MD; Freddie H. Fu, MD, DSci(hon), DPs(hon); Johnny Huard, PhD

Gene therapy has the potential to revolutionize the treatment of a variety of musculoskeletal disorders. In the last decade, more than 4000 patients have been enrolled in clinical trials involving gene therapy. In this article, we define gene therapy and explain why it is becoming increasingly important in modern orthopaedic clinical practice. We also address the issues that physicians and scientists face when designing an experiment or clinical trial involving gene therapy. Finally, we review the potential clinical applications for gene therapy in the treatment of patients with musculoskeletal problems.

What Is Gene Therapy?

In 1998, the Oxford Medical Dictionary defined gene therapy as "the treatment directed to curing genetic disease by introducing normal genes into patients to overcome the effects of defective genes . . ."1 This definition reflects the original premise behind gene therapy, which sprang from the belief that if a defective gene resulting in a specific disease (such as the defective fibrillin gene that causes Marfan syndrome) could be replaced with a healthy gene, then the disease could be cured. The first therapeutic gene-therapy trial in humans began in 1990, with an attempt to treat patients with severe combined immunodeficiency secondary to an adenosine deaminase deficiency2.

More recently, however, the potential role of gene therapy as a clinical tool has expanded. Gene therapy is no longer limited to the replacement of defective genes but rather has become a tool for delivering individual proteins to specific tissues and cells. Although all cells contain the genes for all proteins, cells derived from a particular tissue express only a select few of these proteins. With gene therapy, it is possible to deliver a gene to a given cell that allows the inserted gene product to be expressed constitutively.

Why Is Gene Therapy Important?

This expanded role for gene therapy is particularly important in the musculoskeletal …

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