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New method powerfully boosts efficiency of RNA interference (RNAi) in shutting down genes
Date:2/24/2011

Cold Spring Harbor, N.Y. A research team led by scientists at Cold Spring Harbor Laboratory (CSHL) has developed a powerful method that allows them to sift through thousands of candidate hairpin-shaped RNA molecules at a time and pull out only those RNAs that potently shut down the activity of a target gene. This accomplishment will now allow biologists to fully exploit RNA interference (RNAi), a natural cellular mechanism that has already been co-opted by scientists for myriad purposes such as hunting for cancer genes, stopping viral infections and more recently, treating diseases in clinical trials.

"RNAi is a powerful tool that in theory can be used to knock down any gene of interest but has been difficult to implement in practice," says CSHL Professor and Howard Hughes Medical Institute (HHMI) Investigator Scott Lowe, Ph.D., who co-led the team with Gregory Hannon, Ph.D., also a CSHL Professor and HHMI investigator. One major challenge has been the difficulty of finding the correct molecular trigger for RNAi. The trigger is a tiny piece of RNA, which, by attaching to a matching piece of the target gene's RNA, spurs its destruction, thereby shutting down the production of protein from that gene.

"For every gene, depending on the size of its protein-coding RNA, there are potentially 500 to 5000 different small RNAs that can trigger RNAi," explains Hannon. Most of these are weak triggers that do not shut down gene activity completely or end up targeting a different gene resulting in so-called "off-target" effects. Either scenario can ruin experiments that use RNAi to study diseases in the lab, or worse, lead to useless, or even toxic, treatments in the clinic. "Picking the right trigger has been like trying to pull a needle out of a haystack," Lowe says.

In a paper that appears online on February 24 in the journal Molecular Cell, scientists from the Lowe and Hannon laboratories and their collaborators, including Professor an
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Contact: Hema Bashyam
bashyam@cshl.edu
516-367-6822
Cold Spring Harbor Laboratory
Source:Eurekalert

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