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Designer molecules correct RNA splicing defects: New strategy for treating many diseases

With a high-tech fix for faulty cellular editing, scientists at Cold Spring Harbor Laboratory have moved a step closer to developing treatments for a host of diseases as diverse as breast cancer, muscular dystrophy, and cystic fibrosis.

Many human diseases have been linked to defects in a cellular editing process called pre-messenger RNA splicing. Adrian Krainer, a molecular biologist at Cold Spring Harbor Laboratory, has spent years investigating this complex editing process, which takes the information coded in genes and makes it available for building proteins. In a new study published in the journal Nature Structural Biology, Krainer's team has devised a clever way to correct RNA splicing defects implicated in breast cancer and spinal muscular atrophy (a neurodegenerative disease). In principle, the technique could provide the ability to correct RNA splicing defects associated with any gene or disease.

For now, Krainer's method has been shown to work under the simplest of conditions -- in test tubes with small segments of RNA. The next step is to adapt the technique for use in living cells. Still, "It's a very promising approach," says molecular biologist Brenton Graveley, of the University of Connecticut Health Center. "There are a lot of hurdles to be overcome in terms of delivering the corrective molecules to the cells that need to be treated. But theoretically the exact same approach could be taken for any gene at all, and the list of genes that have defects at the level of RNA splicing is very long," says Graveley, who is familiar with the research but not involved in the study.

For cells to produce protein, DNA is first transcribed into pre-messenger RNA (RNA is a chemical cousin of DNA). Pre-messenger RNA is a "word-for-word" representation of a DNA sequence in the language of RNA. But for reasons that remain unclear to scientists, pre-messenger RNA molecules contain excess "words" that are removed by splicing to create mature me
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Contact: Peter Sherwood
sherwood@cshl.edu
516-367-6947
Cold Spring Harbor Laboratory
12-Jan-2003


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