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Gene therapy may protect donated organs from injury
By Bijal P. Trivedi

Organs suffer damage when they are removed from a donor's body and prepared for transplantation. Temporary loss of blood flow deprives them of oxygen and causes cells to die. Using gene therapy, researchers have found a way to prevent this tissue damage.

Low levels of oxygen increase the activity of the Fas gene, which is known to trigger cell death, or apoptosis. Researchers led by John Fung, of the University of Pittsburgh Medical Center in Pennsylvania, reasoned that blocking the activity of Fas may prevent cell death and help preserve donated organs.

Fung's team delivered antisense DNA—which specifically blocks the activity of the Fas gene—to mice five days before blocking blood flow to the kidney. The flow was blocked for 90 minutes and then allowed to resume.

The loss of blood flow to the kidney for periods as short as 30 minutes dramatically increased the activity of the Fas gene. Substantially fewer dead cells were found in the kidneys of mice that had received the anti-Fas DNA. Normal kidneys express very little Fas and have no dead cells. Fung presented his team's results on Tuesday in Chicago at TRANSPLANT 2001—a joint meeting of the American Society of Transplant Surgeons and the American Society of Transplantation.

Inhibiting activity of Fas with gene therapy may also help minimize tissue damage in stroke and heart attack patients. Fung’s team plans to test whether the anti-Fas therapy works when the organ is actually transplanted from one mouse to another.

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Ma, L. et al. Treatment with antisense oligodeoxyribonucleotides targeting Fas mRNA attenuates renal ischemia-reperfusion injury. TRANSPLANT 2001, the Joint American Transplant Meeting, Chicago, Illinois, USA, May 11-16, 2001.

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