Prevention of HIV-1 infection in human peripheral blood mononuclear cells by specific RNA interference.
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.
Park
Wee-Sung
WS
Department of Industrial Chemistry, Faculty of Engineering, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino-shi, Chiba 275-0016, Japan.
Miyano-Kurosaki
Naoko
N
Hayafune
Masaaki
M
Nakajima
Emiko
E
Matsuzaki
Tetsuo
T
Shimada
Fumiyuki
F
Takaku
Hiroshi
H
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D019556:COS Cells; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015752:Genes, env; D015750:Genes, gag; D016655:HIV Core Protein p24 / Q000096:biosynthesis / Q000235:genetics; D015658:HIV Infections / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D034622:RNA Interference; D016372:RNA, Antisense / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D012367:RNA, Viral / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D016372:RNA, Antisense; D012330:RNA, Double-Stranded; D012367:RNA, Viral