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CSHL team perfects non-lethal way of switching off essential genes in mice
Date:4/14/2011

Cold Spring Harbor, N.Y. -- One way of discovering a gene's function is to switch it off and observe how the loss of its activity affects an organism. If a gene is essential for survival, however, then switching it off permanently will kill the organism before the gene's function can be determined. Researchers at Cold Spring Harbor Laboratory (CSHL) have overcome this problem by using RNA interference (RNAi) technology to temporarily turn off any essential gene in adult mice and then turn it back on before the change kills the animals.

In a study published online on April 12 in the journal Proceedings of the National Academy of Sciences, the scientists demonstrated the feasibility of this approach by turning off a gene necessary for DNA replication in mice until the animals lost weight and were at the brink of death, and then successfully reversing these symptoms and rescuing the mice by turning the gene back on.

The ability to regulate gene activity this way in animals "will not only help in pinpointing timeframes during which essential genes are important during development, but will also be tremendously useful in cancer or other disease-related research," says CSHL Professor and HHMI investigator Scott Lowe, Ph.D., who co-led the team along with Professor Bruce Stillman, Ph.D., CSHL's president. "We could, for example, first allow tumors to grow in mice, then shut off a gene that we think might be a good therapeutic target to test whether it saves the animals," Lowe explains.

To suppress gene activity with RNAi, scientists have been using short hairpin-shaped RNA (shRNA) molecules that attach to matching pieces of the target gene's RNA and trigger its destruction, thereby shutting down the production of protein from that gene. Having refined and optimized the process of using these shRNA to knock down gene activity in mice over the last few years, Lowe and collaborators including CSHL Professor and HHMI investigator Gregor
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Contact: Hema Bashyam
bashyam@cshl.edu
516-367-6822
Cold Spring Harbor Laboratory
Source:Eurekalert  

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