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Researchers pioneer new gene therapy technique using natural repair process

at, in practice, the gene therapy only affects the mutant gene.

Homologous recombination is a fairly rare event that occurs when DNA strands of one chromosome break, creating a damaged section. Cells have two copies of nearly every chromosome (one each from the mother and father) and they must duplicate these during cell division so that the subsequent cells will also have two each. The wounded chromosome takes advantage of the healthy copies created in preparation for division, and uses them as a template to repair the break in the DNA strands.

In the new gene therapy technique, researchers took advantage of homologous recombination by introducing a man-made enzyme that recognizes and binds DNA at specific points into human immune cells harboring the mutant IL-2R gene. Once bound to the mutant gene, the enzyme creates a break in the DNA sequence, initiating the recombination process.

In SCID, as well as many other diseases, both copies of the disease gene are mutated so there is no correct version naturally available. To overcome this, researchers also supplied the cells with a correct version of the IL-2R gene along with the enzyme.

Given the correct copy as a template, the recombination event occurred at the break site and 11 percent of the cells tested had traded one copy of the mutant gene for the correct version. In addition, 6 percent to 7 percent of cells had traded both copies of the bad gene for the correct version.

With the correct IL-2R gene in place, levels of the IL-2R protein also were restored.

The change to the cells seems permanent, Dr. Porteus said, and the correct gene is easily maintained after many cell divisions.

"The rates of correction that we see are extremely exciting," said Dr. Porteus, who was recently awarded a 2004 Distinguished Young Researcher Award from the President's Research Council at UT Southwestern for his early contributions to the gene therapy technique. "That we can fi
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Source:University of Texas Southwestern Medical Center at Dallas


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