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发表于 2002-9-18 00:05
RNAi could hold promise in the treatment of HIV
The Lancet
Volume 359, Number 9322 08 June 2002
The discovery that RNA interference (RNAi) can occur in human cell lines is
little more than a year old, yet the observation is beginning to yield
benefits in terms of research on possible mechanisms to prevent infection ofhuman cells by HIV and other viruses.
This week, US researchers have shown that short interfering RNA (siRNA) cantarget the receptors through which the HIV-1 virus gains entry into humancells and can even reduce the replication of the virus once the infection isunderway (Nat Med; published online 3 June 2002; DOI 10.1038/nm725).
RNAi works by silencing gene expression after the messenger RNA (mRNA) hasbeen transcribed from the host cell's DNA template. Short, double-strandedsegments of siRNA bind to specific locations of the mRNA by complementarybase pairing. After bonding, the siRNA guides the destruction of the
complementary section of the mRNA by an associated enzyme complex, thussilencing the expression of the corresponding gene (see Lancet 2002; 359:682).
"It's a very ancient mechanism that is thought to protect lower organisms
such as plants from transposable elements like viruses", says co-author JudyLieberman (Center for Blood Research, Harvard Medical School, Boston, MA,USA). "It's the first time we've shown that by silencing CD4 expression wecan block infection." Lieberman adds that the test was successful in avariety of cell types, from HeLa cell cultures to T cells obtained fromhuman donors.
John Rossi, (Beckman Research Institute of the City of Hope, Duarte, CA,
USA), who was co-author of a recent paper on the use of RNAi in the
treatment of HIV infection (Nat Biotechnol 2002; 19: 500-05) says that RNAi
is potentially a powerful and precise weapon. "This is a selective mechanismthat will knock out just the virus or whatever we target it to", Rossi says."Using the siRNA approach we can target the entire length of the viralgenome", he adds.
Natasha Caplen (National Human Genome Research Institute, National
Institutes of Health, Bethesda, MD, USA), one of the researchers who
demonstrated RNAi in human cells last year, is encouraged by the way
research in the area is developing. "The big thing is that what you're
seeing is that it not only is an interesting mechanism, but that it has
enormous applications", she says. "It's most likely to be used in the
limitation of infectious disease or carcinogenicity, but it also has
potential application for some dominant genetic disorders."
David Lawrence
RNA interference of HBV gene expression
http://www.hadassah.org.il/departments/gen_ther/sca_rnai_hbv.htm
Human hepatitis B viral infection is widespread and can lead to chronic infection. The number of chronic hepatitis B carriers is estimated to exceed 350 million, with more than one million deaths per year due to associated liver cancer. This virus causes transient and chronic noncytocidal infection of hepatocytes. The chronic liver disease is thought to be largely due to the host immune response, which induces a high level of hepatocyte destruction, leading to disruption of liver function. There is concern that newly emerging viral variants may threaten the efficiency of currently used HBV vaccines and therefore there is a rising need for novel antiviral strategies.
RNA interference (RNAi) is a recently discovered phenomenon, which is based on the observation that double stranded RNA can efficiently inhibit gene expression by promoting selective mRNA degradation. The goal of our research project is to inhibit the production of HBs antigen of HBV by expressing a specific dsRNA transcript in virus infected cells. This technology may provide new anti-viral strategies and lead to the development of novel anti-HBV therapies.
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