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A novel, safer strategy for regulating gene expression

Researchers at Children's Hospital Boston and Harvard Medical School have created a novel, elegant, and safer system for controlling gene expression turning genes on and off as needed that involves an intervention as simple as giving a drug. Potentially, with this technique, a gene could even be activated by natural conditions in the body for example, in a diabetic patient, a rise in glucose concentration would automatically turn on the gene responsible for insulin production.

The system, described in a proof-of-principle paper in the Sept. 23 edition of the journal Nature, is simpler than current methods of gene regulation, and the technology exists to make it work with virtually any drug, making it suitable for a broad range of therapeutic and research applications.

The technique involves inserting a special DNA sequence into a patient's own genes, or into a gene introduced by gene therapy. This sequence encodes a ribozyme, a sequence of RNA that has the unique ability to spontaneously cut itself in half. The ribozyme becomes part of the gene's messenger RNA (mRNA), the template that carries instructions for making the protein encoded by that gene. When the ribozyme cuts itself in half, the mRNA is cut in half, too disabling it and, in effect, turning off the gene. Inhibiting ribozyme breakage, which can be done with various drugs, leaves the mRNA intact; this allows the gene to turn "on" and make the desired protein such as a hormone or growth factor needed by the body.

"Perhaps the most exciting aspect of the new work is that, in conjunction with other technologies, we will likely be able to 'tailor' gene regulation systems to respond to any drug or chemical," says Dr. Richard Mulligan, director of gene therapy research at Children's Hospital Boston and director of the Harvard Gene Therapy Initiative. "Ultimately, the system should also enable the 'release' of a therapeutically useful protein in response to changing concentrat
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Contact: Aaron Patnode
aaron.patnode@childrens.harvard.edu
617-355-6420
Children's Hospital Boston
22-Sep-2004


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