Scientists develop new RNAi knockdown ...( Scientists from the RIKEN Tsukuba Insti...)

Discovered in the late nineties, RNA intereference (RNAi) refers to the introduction of double-stranded RNA (dsRNA) into a cell, where it induces the degradation of complementary mRNA, and thereby suppresses gene expression. RNAi has proven to be a powerful tool in the elucidation of gene function in organisms ranging from worms, to plants and fruit flies.

However, the use of RNAi in mammals has been complicated by the antiviral response of mammalian cells to dsRNA. The presence of foreign dsRNA in a mammalian cell initiates the so-called "interferon response:" the non-specific degradation of mRNA, and ensuing death of the cell. Mammalian RNAi researchers have undertaken a few different routes to avoid eliciting the interferon response, and while some have been successful, none have been able to accomplish it in a tissue-specific manner. Until now.

As published in the June 1 issue of Genes & Development, Dr. Shunsuke Ishii and colleagues have constructed a new RNAi vector (a vehicle to introduce foreign RNA into a cell), which both side steps the interferon response and allows for the tissue-specific suppression of gene expression. This vector, called pDECAP, represents a dramatic improvement over current RNAi transgenic technology.

As Dr. Ishii explains, "In the RNAi transgenic systems developed so far, small hairpin-type RNA is expressed from the RNA polymerase III promoter or the virus promoter. However, these systems cannot be utilized to knockdown gene function in a tissue-specific manner, because these promoters are active in all types of cells. In our system, the RNA polymerase II promoter is utilized to express hairpin-type double-strand RNA (
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Contact: Heather Cosel
coselpie@cshl.org
Cold Spring Harbor Laboratory
31-May-2003