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Study first to show potential of light-activated gene therapy for knee injuries

ridement relieve pain and inflammation, but leave a hole in the cartilage. Other techniques are too expensive and invasive or apply to few injuries, according to the study authors. Given the limits of surgical repair, researchers have been attempting for years to use gene therapy to truly repair, or re-grow, articular cartilage.

The blueprint for the human body is encoded in genes, which store information that is converted into proteins which carry out bodily functions. Gene therapy works by inserting specially designed genes into cells that can, for instance, direct cells to divide, which makes a tissue grow. Animals like amphibians re-grow amputated limbs, including articular cartilage, but humans grow cartilage only once, during development, without help.

To deliver the genes into cells, researchers need an effective delivery vehicle, or vector. Viruses have evolved for millions of years to invade human cells and insert DNA into their prey. Researchers have harnessed their useful qualities while removing the harmful ones. Unfortunately, no viral vector to date has been able to turn on genes only in the damaged areas because they infect cells in nearby healthy tissue as well.

Sunlight: A Specific Solution

The solution to the problem of how to target some cells for gene therapy, while missing their neighbors, came from a strange source: our cellular defenses against sunlight. The sun gives off ultraviolet (UV) light, which can cause destructive changes (genetic mutations) when exposed to sensitive molecules like DNA. If not defended against, the changes in DNA caused by UV light would cause humans to constantly develop cancer, for instance, in exposed tissue. Thus, an SOS system evolved that calls for genetic repairs when UV light causes too many mutations. Specifically, UV light turns on signaling proteins called stress kinases, which activate DNA polymerase, the enzyme that re-builds DNA chains when damaged.


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Contact: Greg Williams
Greg_Williams@urmc.rochester.edu
University of Rochester Medical Center
24-Apr-2006


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