A decade and a half back, RNA was a mere spark in the eyes of scientists. But today researchers throughout the world have realized the importance of Ribonucleic acids as they are reckoned as a potential base factor in curing diseases ranging from the common cold to the more vicious ones like AIDS and cancer.

Why the interest in RNA?

RNA was earlier thought of as only a messenger in the cell. But now it turns out that it is much more than that. It's a manager and a key regulator as well. RNA is probably one of the greatest discoveries of the last decade, and this is further reinforced by the fact that gene silencing by RNA interference was the topic that won the 2006 Nobel Prize for two American scientists.

Earlier the idea was that RNA just carried the protein blueprint from DNA to ribosomes and for assembling required protein molecules. But now it's been established that RNA not only does these things but can shut off the blueprint carrying gene itself. An important discovery is that, amongst non-coding RNA functions are micro RNAs and riboswitches, which means RNA has a bigger role than earlier thought of.

RNA Uses

Every cell has hundreds of RNA doing different functions, as for example turning on and off processes and regulating what combines with what. For example, when a virus attacks the cells it injects RNA that RNA interface destroys. Genes encoding micro RNA control processes entailing protein synthesis. After processing, micro RNA blocks m-RNA translation to protein. Furthermore, s-RNA molecules can be tailor made to activate the RISC complex to degrade m-RNA for a specific gene.

RNA Interference

Dr. Rich Jorgensen first discovered RNA interference in petunias in his search to intensify the color of the flower by adding copies of enzymes that aid in pigmentation. However, instead of intensifying the colors faded and much later this phenomenon was attributed to the creation of double stranded RNA that supposedly caused the reduced expression of target gene.

RNA interference (RNAi) is a natural conserved mechanism by which small interfering RNA (siRNA) downregulate the expression of a target gene also at the level of transcription and not predominantly at the level of m RNA. RNA interference (RNAi) or gene silencing means the use of double stranded dsRNA that once inside the cell converts to short nucleotide RNAs termed siRNAs that are used in a specific manner to recognize and destroy complementary RNA. Although it's generally believed that Dicer is necessary for processing of precursor microRNAs, now it has been established that it could also be done with the help of Argonaute 2.

RNA-i Uses

RNAi technology is currently used in diagnostic reagents and several RNAi-based products are undergoing clinical trials for therapeutic use. Conventional medicines can only target limited number of proteins in disease pathways but perhaps RNA-based medicines could increase the number of targets addressed.

Gene therapy using RNA to treat diseases is a possibility as for example setting right genetic defects by giving injections of certain proteins so the body itself makes required proteins; or using RNA pieces to block mutated genes. The latter (blocking mutated genes) can be therapeutically used in combating various illnesses including cancer. But the problem that could be encountered is side effects due to non-specific interaction between siRNA compound and an unrelated host gene.

Once the gene sequence is known RNAi can silence any gene and therefore RNAi is an important research method for analyzing gene function and identifying new drug targets. For example after sequencing the genome of an organism RNAi can target every gene in the genome to study its traits such as morphology and physiological properties.

Research efforts in RNA therapeutics

Several companies are pursuing research in developing delivery mechanisms for therapies based on RNA which no doubt emphasizes the importance of RNA as a therapeutic tool.

Alnylam set up by Nobel laureate Philip Sharp specializes in developing RNAi therapeutic targeting transthyretin (TTR) for treating TTR amyloidosis. The only present option for patients with TTR amyloidosis is liver transplantation but this promising RNAi technology helps reduce both m RNA in the liver and circulating TTR protein.

Another research effort of Alnylam is in developing ALN-PCS, an RNAi therapeutic considered better than statin drugs in treating hypercholesterolemia. ALN-PCS works by silencing the gene PCSK9 considered responsible for causing hypercholesterolemia.

Santaris Pharma A/S has advanced a microRNA-targeted drug SPC3649 (targets miR-122) into human clinical trials for treatment of Hepatitis C

Benitec with its novel RNAi technology introduces specially engineered, HIV-fighting genes into the patient's cells to fight both HIV blood stem cells of the patient and also targets their T-cells. This multi-target approach reduces the chances of HIV resistance.

Cequent with its proprietary TransKingdom RNA interference (tkRNAi) technology has products now in pre-clinical development to target colon-cancer prevention and inflammatory bowel disease. tkRNAi technology deactivates specific disease-causing genes using non-pathogenic bacteria to produce and deliver RNAi directly into cells.

Dicerna Pharmaceuticals uses its proprietary Dicer Substrate Technologyâ„¢, to triggers RNA interference (RNAi) to knock down the expression of a targeted gene in highly selective way and therefore more potent and different from other RNAi approaches.


Especially with the spurt in metabolic diseases RNA therapies have the potential to become multi billion dollars businesses in their own right. Even big pharma is in pursuit of research based companies focusing on RNA. For example, Merck purchased Sirna Therapeutics which specializes in RNAi technologies. Although actual therapies have still to be approved RNA is thought to be a hot topic.

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