Decades of genetics research have revealed a wealth of information about the molecules that make life. Owing to technical limitations of human and other mammalian cells, sophisticated genetic experiments have typically been possible only in "model" organisms such as baker's yeast, fruit flies, and nematode worms. Fundamental discoveries in these organisms can subsequently be applied to human cells, but even then, the process is laborious.
Researchers at Cold Spring Harbor Laboratory (CSHL) are working to change that state of affairs. In a study published in the February 5 issue of the Proceedings of the National Academy of Sciences, CSHL scientist Gregory Hannon and his colleagues report a new technique for carrying out genetic analysis directly in mammalian cells. The technique has the potential to greatly simplify gene manipulation and gene discovery for many biomedical applications.
"This technique could save months of work per gene," said Steven Elledge, of Baylor College of Medicine, who is familiar with the study.
Hannon and his colleagues have recently developed a convenient strategy that enables them to switch off any gene (or combination of genes) in mouse cells, in either a targeted or a random fashion. With this ability to switch genes off (or to switch them on, indirectly), researchers can do several things.
They can infer the function of a particular gene by determining what happens to cells when that gene is switched off. In addition, by switching genes off at random, researchers can select those cells that display interesting new properties, such as improved response to cancer treatment. The latter, unbiased approach is an attractive way to identify genes that are potential targets for new cancer therapies or treatments for other diseases.
The new study, which appears January 29 in an on-line, "Early Edition" of the Proceedings of the National Academy of Sciences (http://www.pnas.org/papbyrecent.shtml), was funded by the National Institutes of Health and by the Cambridge, Massachusetts biotechnology company Genetica, Inc. Dr. Hannon, a co-founder of Genetica, is building on the results of the study to explore ways to selectively destroy cancer cells.
Using a strategy related to that developed by the Cold Spring Harbor Laboratory group, Thomas Tuschl of the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, achieved similar results in a study published last May in Nature. However, the Cold Spring Harbor Laboratory strategy for switching genes off in mammalian cells appeared to produce more stable, longer-lasting effects than those observed in the earlier study.
True geneticists working with yeast, flies, and worms still have much to contribute to dissecting the complex genetic networks that control life. However, the new technique may well inspire researchers working with human and other mammalian cells to attempt genetic-style experiments that they could only have dreamed of just a few years ago.
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Peter W. Sherwood, Ph.D.
Patrick J. Paddison, Amy A. Caudy, and Gregory J. Hannon
Stable suppression of gene expression by RNAi in mammalian cells
PNAS 99: 1443-1448; published online before print as 10.1073/pnas.032652399
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