RNA Interference as a Therapeutic Agent for Asthma
 
    RNA interference, the silencing of genes by double-stranded RNA (dsRNA), was discovered in nematode worms by Andrew Fire and Craig Mello in 1998. RNAi is an evolutionarily ancient mechanism of defense against viruses and also a mechanism of self-regulation. The concept is fairly simple. When double-stranded RNA, i.e. from a virus carrying a transgene, or a synthetic dsRNA for RNAi therapy is introduced into the cell, an enzyme called Dicer works to slice it up into oligonucleotides 21-22 nucleotides long, called short interfering RNA’s (siRNAs). Subsequently, the dsRNA is coupled with an RNA-induced silencing complex (RISC), which degrades the sense strand (identical to the target mRNA). The RISC/antisense siRNA complex binds to a complementary mRNA and targets it for destruction. Consequently, the gene associated with that mRNA is silenced.3 
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RNA interference: An Introduction RNA Interference Mechanism
courtesy of www.nature.com
    There is a second class of oligonucleotides that are involved in a different mechanism of siRNA. MicroRNA’s are RNA’s encoded by the cell itself to silence genes at the translational level. They are single-stranded RNA’s that are self-complementary (fold into a hairpin). They are encoded by the cell itself and bind to the complementary mRNA’s in the cell. They essentially block the mRNA from being read and translated into protein in the ribosomes. Short hairpin  (shRNA’s), the synthetic version of miRNA’s attempts to mimic this in vivo mechanism. shRNA’s can also be cleaved into siRNA’s in vivo.

    In basic science, RNAi allows high throughput studies of gene function: studying gene networks, development, and cell signaling without the dependence on the slow reproduction of animals. In clinical science, RNAi shows promise as a direct therapeutic for almost any disease. The advantage is that RNAi seeks out and destroys its target gene without affecting other genes.
   
 siRNA’s can be easily synthesized by T7 phage RNA polymerase in vitro transcription from short double-stranded oligo cassettes containing a promoter sequence.4 However, this process requires selection of the siRNA of interest. To eliminate this step, recombinant Dicer can be used in vitro to create an array of siRNA’s of interest.
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Novina CD et al. Nature.(2004)