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Novel Method Of Gene Replacement Reported By University Of Washington Researchers

Dr. David W. Russell, assistant professor of medicine, and Roli Hirata, research technician at the University of Washington, report the successful use of a modified virus to perform a novel method of gene replacement that may be an important step toward overcoming obstacles to efficient gene therapy. Their findings are reported in the April issue of Nature Genetics.

Until now, gene therapy researchers have focused on gene addition, using a variety of modified viruses as vectors or transport vehicles to "infect" and insert the proper genetic material into cell nuclei that have genes with undesirable mutations. While the proper genetic material is inserted, it goes to random locations on the chromosome, and the faulty genetic material also remains.

By contrast, Russell and Hirata were able to achieve efficient gene correction. They succeeded in targeting the exact location of the mutated gene on the chromosome and replacing it with the correct genetic material present in the viral vector, at exactly the right location.

Russell uses a typewriter analogy: the new method finds the typographical error, whites it out and types in the proper sequence in the right place.

"If you had a 'typo' in a financial statement, say a missing zero, you'd want to fix in the right place, not randomly anywhere in the statement," he explains. "Or if you were correcting an instruction booklet with an error in it, you'd want to insert the corrected instruction in the right place on the right page."

The UW researchers' method guarantees that the new gene is controlled by appropriate genetic circuitry, ensuring that it is switched on in the right cells, at the right time and at the right dosage.

In addition to targeting exactly the right part of the cell, the repaired copy and the mutated copy of the genetic materal were exchanged at what researchers consider a very high frequency, in approximately 1 percent of ta
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Contact: Dr. David W. Russell
drussell@u.washington.edu
(206) 616-4562
University of Washington
30-Mar-1998


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