Improved Vector Expresses Long Double-Strand RNA

Scientists have reported the development of a vector for insertion of double-strand RNA (ds-RNA) for use in RNAi (RNA interference) gene control in a tissue-specific manner that does not trigger the interferon response, which non-specifically degrades mRNA (messenger RNA) in response to the presence of ds-RNA in the cell.
This vector, called pDECAP, is able to express long ds-RNA from an RNA polymerase II (Pol II) promoter. It was developed by researchers at the Riken Tsukuba Institute (Japan) and was described in the June 1, 2003, issue of Genes & Development.

Since the transcripts from pDECAP lack both the 5'-cap structure and the 3'-poly(A) tail that facilitate ds-RNA export to the cytoplasm, long ds-RNA from pDECAP does not induce the interferon response. Transgenic mice embryos expressing long ds-RNA for the transcriptional co-repressor Ski from this vector exhibited phenotypes that were remarkably similar to those of Ski-deficient embryos, including defects of neural tube closure and eye formation.

Senior author Dr. Shunsuke Ishii, a senior researcher at the Riken Tsukuba Institute explained, "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 knock down 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 (ds-RNA). Therefore, our system can be used to generate the tissue-specific knock-down mice.”




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Riken Tsukuba Institute