What is the benefit of si RNA?

Ganseerpel

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What is the benefit of si RNA?

November 30, 2006, 01:40 PM

There was a time simple RNA molecules were regarded as simple ?intermediates? between DNA and the proteins. Since the nineties we know that double stranded RNA (dsRNA) is able to inhibit gene expression and controls important cell functions.

When dsRNA molecules are composed or injected in a cell they are cut into small pieces of 25 bp?s (Dicer). These small double stranded RNA (small interference RNA) fragments interact with a proteine complex called Risc, which destroys the ?positive? RNA strand. The complementary strand (cRNA) directs the complex to a piece of complementary mRNA that will be dismantled in the same way. <?xml:namespace prefix = o ns = "urn:schemas-microsoft-com[IMG]http://www.flutrackers.com/forum/ /><o:p></o:p><o:p></o:p>Thus siRNA?s prevent translation of mRNA - which can be used in blocking viral mRNA?s <o:p></o:p> ******************** Published online before print June 1, 2004, 10.1073/pnas.0402630101 PNAS | June 8, 2004 | vol. 101 | no. 23 | 8682-8686 <TABLE class=content_box_outer_table align=right><TBODY><TR><TD></TD></TR></TBODY></TABLE> MEDICAL SCIENCESProtection against lethal influenza virus challenge by RNA interference in vivo Stephen Mark Tompkins *, Chia-Yun Lo *, Terrence M. Tumpey <IMG alt=[/IMG], and Suzanne L. Epstein *, 
*Laboratory of Immunology and Developmental Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892; and Influenza Branch, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333
Communicated by Herman N. Eisen, Massachusetts Institute of Technology, Cambridge, MA, April 13, 2004 (received for review March 18, 2003)

<TABLE cellSpacing=0 cellPadding=0 width="100%" bgColor=#e1e1e1><TBODY><TR><TD vAlign=center align=left width="5%" bgColor=#ffffff></TD><TH vAlign=center align=left width="95%">Abstract </TH></TR></TBODY></TABLE><TABLE cellPadding=5 align=right border=1><TBODY><TR><TH align=left>Top
Abstract
Materials and Methods
Results and Discussion
References

</TH></TR></TBODY></TABLE>
Influenza virus infection is responsible for hundreds of thousands of deaths annually. Current vaccination strategies and antiviral drugs provide limited protection; therefore, new strategies are needed. RNA interference is an effective means of suppressing virus replication in vitro. Here we demonstrate that treatment with small interfering RNAs (siRNAs) specific for highly conserved regions of the nucleoprotein or acidic polymerase inhibits influenza A virus replication in vivo. Delivery of these siRNAs significantly reduced lung virus titers in infected mice and protected animals from lethal challenge. This protection was specific and not mediated by an antiviral IFN response. Moreover, influenza-specific siRNA treatment was broadly effective and protected animals against lethal challenge with highly pathogenic avian influenza A viruses of the H5 and H7 subtypes. These results indicate that RNA interference is promising for control of influenza virus infection, as well as other viral infections. 

<HR align=center width="50%" noShade SIZE=1>Influenza virus infection is a major public health problem, causing millions of cases of severe illness and as many as 500,000 deaths each year worldwide (1). Although inactivated vaccines are 60?80% effective against matched influenza strains (2), vaccination coverage is a problem worldwide. Moreover, this strategy provides no protection against unexpected strains, outbreaks such as the H5 and H7 avian influenza outbreaks in Hong Kong in 1997 and The Netherlands and Southeast Asia in 2003?2004, or pandemics. Currently, antiviral drugs are the best defense against these outbreaks, but they too provide only partial protection (3). New therapies to treat ongoing influenza infection are urgently needed, as well as new vaccination strategies inducing broader immunity (1, 4, 5). 

RNA interference (RNAi) is an emerging technology that specifically inhibits gene expression. Small interfering RNAs (siRNAs), mediators of RNAi, are short (21?26 nt), double-stranded RNA duplexes that inhibit gene expression by inducing sequence-specific degradation of homologous mRNA (6). Many studies have shown that siRNA can significantly suppress gene expression when delivered into mammalian cells in vitro (7, 8). These findings raised the possibility that RNAi could inhibit viral gene expression and protect cells from viral infection. Subsequently, a number of studies demonstrated inhibition of replication of RNA viruses in vitro by RNAi (9?11), including HIV (12, 13), polio virus (14), hepatitis C virus (15, 16), West Nile virus (17), and influenza virus (17, 18). Moreover, a number of groups demonstrated effective silencing of both transgene and endogenous gene expression in vivo (19?25). Here we extend these studies to an animal model of virus infection and disease. We show that administration of influenza-specific siRNAs can decrease lung virus titers and protect mice from lethal challenge with a variety of influenza A viruses, including potential pandemic subtypes H5 and H7. This inhibition of influenza virus replication is specific, requiring homology between the siRNAs and gene targets, and is not the result of IFN induction by double-stranded RNA. 

Full text http://www.pnas.org/cgi/content/full/101/23/8682
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What is the benefit of si RNA?