New RNA interference technique can silence up to 5 genes

RNAi is a natural process with exquisite specificity. The RNAi pathway is typically initiated by molecules referred to as small interfering RNAs (siRNAs). siRNAs are double-stranded RNA molecules that when

bound to a protein complex called the RNA Induced Silencing Complex (RISC) are able to down regulate, or silence, a single gene in a sequence-specific manner by degradation of the target mRNA.The RNAi process is initiated when a cell encounters dsRNA from an agent that enters the cellular cytoplasm such as viral RNA, a transposon, or microRNA. When this occurs, the RNase III-like protein Dicer is guided to the agent. Dicer cleaves the long dsRNA molecules into siRNA fragments 20 - 25 base pairs in length. The siRNA is then incorporated into the RNA-induced silencing complex (RISC) where the duplex is unwound into two strands. One of these strands (the guide strand) pairs with a complementary mRNA sequence, resulting in site-specific cleavage and silencing of the mRNA message. As the mRNA is degraded, the siRNA-RISC complex is released to pair with another mRNA target. Degradation of the mRNA reduces expression levels of the corresponding protein, effectively downregulating (silencing) the gene without altering

the DNA. It is this down-regulating action of RNAi that make siRNAs attractive as both a research tool and a potential therapeutic mechanism for treating diseases characterized by abnormal protein production. Researchers at MIT and Alnylam Pharmaceuticals report that they have successfully used RNA interference to turn off multiple genes in the livers of mice, an advance that could lead to new treatments for diseases of the liver and other organs. Since the 1998 discovery of RNA interference — the naturally occurring phenomenon in which the flow of genetic information from a cell's nucleus to the protein-building machinery of the cell is disrupted — scientists have been pursuing the tantalizing ability to shut off any gene in the body. Specifically, they have been trying to silence malfunctioning genes that cause diseases such as cancer.

Full story available in Helix Feb-March 2010

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