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The high sequence specificity of RNA interference may make it suitable to treat diseases that are linked to selective or elevated expression of particular identified genes, such as in pancreatic cancer
The antiapoptotic gene Bcl-2 has been a target for downregulation by nucleic acid based strategies for more than a decade but the recent failure of the synthetic antisense oligonucleotide agent Genasense in phase III clinical trial caused many to think again about the worth of this approach. However, a new optimism about this and other targets is spreading through the community following several encouraging applications of the recently discovered technology of RNA interference, which is essentially a new biological version of the antisense system.1
RNA interference is considered to have begun as an evolutionarily ancient mechanism for protecting organisms from viruses. Many viruses have RNA, rather than DNA, as their genetic material and go through at least one stage in their life cycle in which they make double stranded RNA. Perhaps not surprisingly, all multicellular organisms have evolved a well conserved protein apparatus that destroys double stranded RNA but this has also been found to play a role in maintenance of the organism’s own genome stability by suppressing the movement of mobile genetic elements, such as transposons and repetitive sequences.
The gene silencing process of RNA interference (RNAi) involves the manufacture of short double stranded RNA molecules by an enzyme called DICER, which cleaves RNA duplexes into 21–26 base pair oligomers. These small interfering …
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Conflict of interest: None declared.