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Nucleic Acids Research, 2002, Vol. 30, No. 22 4830-4835
© 2002 Oxford University Press

Prevention of HIV-1 infection in human peripheral blood mononuclear cells by specific RNA interference

Wee-Sung Park1, Naoko Miyano-Kurosaki1,2, Masaaki Hayafune1, Emiko Nakajima1, Tetsuo Matsuzaki3, Fumiyuki Shimada3 and Hiroshi Takaku*,1,2

1 Department of Industrial Chemistry, Faculty of Engineering and 2 High Technology Research Center, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino-shi, Chiba 275-0016, Japan and 3 Japanese Red Cross Society, 690 Toyotomi-cho, Funabashi-shi, Chiba 274-0053, Japan

*To whom correspondence should be addressed. Tel: +81 47 478 0407; Fax: +81 47 471 8764; Email: takaku{at}ic.it-chiba.ac.jp

The RNA interference (RNAi) phenomenon is a recently observed process in which the introduction of a double-stranded RNA (dsRNA) into a cell causes the specific degradation of a mRNA containing the same sequence. The 21–23 nt guide RNAs, generated by RNase III cleavage from longer dsRNAs, are associated with sequence-specific mRNA degradation. Here, we show that dsRNA specifically suppresses the expression of HIV-1 genes. To study dsRNA-mediated gene interference in HIV-1-infected cells, we have designed six long dsRNAs containing the HIV-1 gag and env genes. HIV-1 replication was totally suppressed in a sequence-specific manner by the dsRNAs in HIV-1-infected cells. Especially, E2 dsRNA containing the major CD4-binding domain sequence of gp120, as the target of the HIV-1 env gene, dramatically inhibited the expression of the HIV-1 p24 antigen in PBMCs for a relatively long time. The dsRNA interference method seems to be a promising new strategy for anti-HIV-1 gene therapeutics.


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