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Cold Spring Team Reports That RNA Interference Can Suppress Gene Expression

NEW YORK, Jan. 29 - RNA interference may be used to stably suppress mammalian gene expression, according to a paper published in the current issue of Proceedings of the National Academy of Sciences.

The research, carried out by scientists at Cold Spring Harbor Laboratory, is also being commercialized as  a high-throughput target validation tool by Genetica, a company founded by Cold Spring researchers.


Genetica founder Gregory Hannon said in a statement that the value of RNAi in mammalian cells came from its capacity to generate persistent "loss of function" phenotypes that can be useful for drug-target identification and validation. Furthermore, it may be possible to create stable "knock-down" cell lines that can be used to examine phenotypes that develop over a long period of time.


The RNAi method, a type of post-transcriptional gene silencing, has generated interest as a tool in functional genomics. In RNAi, double-stranded RNA is introduced into cultured cells where it is digested into shorter guide RNAs. Those segments form an RNA-induced silencing complex that targets and cleaves endogenous mRNA.


Hannon said that the technique was previously only workable in plants and models like Drosophila and C. elegans. RNAi has been induced in cultured mammalian cells before, but only with short 21-23 base-pair segments of double-stranded RNA.


The researchers, funded by Genetica and the US National Institute of Health, were able to trigger gene silencing with longer 500-base-pair dsRNA segments. Further, the paper shows that RNAi can silence expression in a range of cells, including embryonic stem cells and some somatic cells.


The paper, "Stable Suppression of Gene Expression by RNAi in Mammalian Cells," is in the Jan. 29 issue of PNAS.


Privately held Genetica, based in Cambridge, Mass., was formed in 1998 by Cold Spring Harbor researchers Hannon and David Beach.

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