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Menisci Are Efficiently Transduced by Recombinant Adeno-Associated Virus Vectors In Vitro and In Vivo

Henning Madry, MD^*,, Magali Cucchiarini, PhD, Gunter Kaul, PhD, Dieter Kohn, MD, Ernest F. Terwilliger and Stephen B. Trippel, MD

From the Laboratory for Experimental Orthopaedics, Department of Orthopaedic Surgery, Saarland University, Homburg, Germany, the Division of Experimental Medicine, Harvard Institutes of Medicine, Harvard University, Boston, Massachusetts, and Indiana University, Indianapolis, Indiana

^* Address correspondence to Henning Madry, MD, Laboratory for Experimental Orthopaedics, Department of Orthopaedic Surgery, Saarland University Medical Center, 66421 Homburg, Germany (e-mail: hmad{at}hotmail.com).

Background: Meniscal tears remain an unsolved problem in sports medicine. Gene transfer is a potential approach to enhancing meniscal repair. Recombinant adeno-associated virus is a method of gene transfer that has advantages over previously used approaches to this problem.

Hypothesis: Direct gene transfer to meniscal cells can be accomplished using recombinant adeno-associated virus in vitro and in vivo.

Study Design: Controlled laboratory study.

Methods: Recombinant adeno-associated viruses containing the reporter gene lacZ were tested for their ability to achieve gene transfer into lapine and human meniscal cells in vitro and into lapine meniscal defects in vivo. Results were assessed by detecting ß-galactosidase, the enzyme encoded by the lacZ gene.

Results: Maximal efficiency of gene transfer was 81.6% ± 6.6% for lapine and 87.2% ± 14.8% for human meniscal cells in vitro. Expression of the transferred gene continued for the 28-day duration of the study. When the recombinant adeno-associated virus vector was injected into meniscal tears in a lapine meniscal tear model, transgene expression continued in meniscal cells adjacent to the tear for at least 20 days in vivo.

Conclusions: The data suggest that recombinant adeno-associated virus vectors can directly and efficiently transfer and stably express foreign genes in isolated lapine and human meniscal cells in vitro and in lapine meniscal defects in vivo.

Clinical Relevance: This direct gene transfer approach may form a basis for improved treatments of meniscal tears.

Key Words: meniscal tears • recombinant adeno-associated virus (rAAV) vectors • gene transfer • rabbit • meniscal cells