In a world first, a TGRI team led by Dr. Shaf Keshavjee has successfully used gene therapy to repair previously unsuitable donor lungs for transplantation. The eloquent series of investigations, conducted outside the body, were used to probe inflammation and organ rejection, two main complications after transplant surgery.

Explains first author Dr. Marcelo Cypel, "Anything we can do to prevent lung injury, especially in the first 72 critical hours after surgery, would have a significant impact on survival and quality of life after transplantation."

Studies were conducted in large animal and human models of end-stage lung disease. Using an innovative procedure that was developed by the team, donor lungs were maintained at normal body temperature and administered IL-10 gene therapy. IL-10 was the chosen gene therapy candidate specifically for its anti-inflammatory capabilities.

Findings showed that lungs treated with IL-10 gene therapy had significantly improved blood flow throughout the organ and were considerably better at taking in fresh oxygen and removing carbon dioxide. In fact, the effect was so significant it lasted up to 30 days post-surgery.

"We are very excited," says Dr. Keshavjee. "It is as if gene therapy 'turbocharges' each individual cell to manufacture many more proteins in its own IL-10 factory. This protein decreases the inflammatory potential of cells injured before and during the transplant process. It also has the capacity to turn down the recipient's immune system, which rejects the transplanted organ."

Cypel, M., Liu, M., Rubacha, M., Yeung, J.C., Hirayama, S., Anraku, M., Sato, M., Medin, J., Davidson, B., de Perrot, M., Waddell, T.K., Slutsky, A.S., and Keshavjee, S. Sci Transl Med 28 October 2009: Vol. 1, Issue 4, p. 4ra9. [Pubmed abstract]. Research supported by the Canadian Institutes of Health Research, and the Center for Gene Therapy National Institutes of Health.