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RNAi: A billion dollar baby

Dr.Utpal BhadraThursday, November 30, 2006, 08:00 Hrs  [IST]

RNA world in live cells pave a new avenue in biological Science. Its impact in basic scienence revolutionarises our conventional concept of biology. Truly speaking "any thing DNA can do, RNA can do better". RNA based medicines are running towords the clinic to challenge the conventional drugs and target the bugs that has no cure. In remuneration, RNAi mechanism receives quickest noble prize in medicine and physiology in 2006 after its discovery in 1997. A couple scientists in India are closely working on its discovery in animals and narrowly missed nobel prize for their enormous contributions. Currently, RNAi technology is treated as a billion dollar baby developing new therapy to biotech Industries. The exploitation of DNA molecules in different biochemical techniques ultimately gifted us a sequence of human genome. This blueprint of life contains nearly 25000-30000 genes. It raises an obvious question in our mind "can 25000-30000 genes in human sufficient for our every days activity? This question has opened up a new dawn in modern molecular biology The RNA world. In recent days, the wide range of ribonucleic acid (RNA) outplayed DNA from the field of development, disease and human health. The small regulatory RNA is turning out to be a major player involved in most vital activities of human cell. In practice, the RNA which was long viewed as a mere copyist of the gene encoded by the famous double helix has come into lime light. It looks DNA is just a passive archive of information identical to old page of telephone directory, whereas RNA is an active partner and dial not only the phone numbers but establishes the connection and the time of each call. Through central dogma in which RNA makes messenger RNA that ultimately encodes the proteins for each and every activity of life is still unchallenged. But that dogma has began to appear less comprehensive after explosion of findings about regulatory RNA that was produced by animal, plant, bacteria and viruses etc. Small regulatory RNA is turning out to play a major role involved in most vital activities in human cell by silencing the homologous gene based on sequence similarity. These RNA-RNA interference that is referred as RNAi, is a readymade knock down system applied in silencing of an innumerable number of genes. It protects the intriguity of DNA in tumor cells, cellular differentiation, development, chromatin organization, rapid cell proliferation, tumor formation and many more. Its application in human based defect in different diseases are now in reality. RNAi genome drugs are running towards the clinic. Moreover, the new role of RNA promotes to emerge by the discovery of different regulatory RNAs including silencing RNA, repeat associated RNA, microRNAs, non-coding RNAs etc. Though there are only 400 microRNAs in human genome message in relation to 25000 non-coding genes in humans, each microRNA can interfere with many kinds of messenger RNA. This imposes an evolutionary constraint on all the cell's messenger RNAs because the gene that do not meet through protein to be controlled by microRNA. More than one third of the human genes have felt evolutionary pressure to maintain the sequences in their messenger RNAs that can be controlled by regulatory RNAs because regulatory RNAs can elimiate messenger RNAs at a time in a specific tissue. The small RNAs can be used as guide for destroying the machinery of infectious organisms once they enter our body. Yet doctors, clinical researchers are now talking about beginning human trials within the next two or three years - an amazing rate of success or progress. Part of the excitement also stems from the power of RNAi. It has a capacity to destroy any genetic materials at any time point of our life in any specific type of cells that is thought to be appeared as gene knock out system. When RNA viruses infect our body they make double-stranded copies of their genetic material for making replica. In response, our defense mechanism triggers and fights back. These double-stranded viral RNA is chopped into small pieces of genetic code containing nearly 22 letters by a biological scissor, Dicer, commonly known as RNAase III enzyme. The small RNA duplex that floats in the live cells as isolated fragments, eventually binds to single stretch of same viral RNA based on their similarity. Finally the same Dicer molecule and related proteins target the double stranded viral RNA and destroy them into degraded fractions. Therefore, the RNA killing process shuts off key viral genes, which are potentially, nipped infectious buds in our body. As soon as this strategy identifies in human, clinicians exploits it in different areas as a magic bullet. RNAi therapy for curing any diseases appears to a gold mine in Biotech Industries. Its achievement in curing wide spectrum of diseases, cancer to neurodegenerative diseases, Rheumatoid arthritis to AIDS, Diabetes to Cardiovascular disorders and viral infection to cosmetic treatments makes it most promising medicine in modern era. A new role of RNAi in DNA and proteins packaging required for rapid cell division keeps our hope for readymade cancer therapy in near future. Meanwhile most of the clinical interest lies on its routine applications for combating viral and foreign DNA to propagate inside the live cells. One of the obvious targets is HIV - a virus that has no cure and no vaccine so far. Several research groups' targets different HIV genes related to their replication in human cells and is reduced dramatically. Same technique is applicable for other virus born diseases for example hepatitis C, polio, influenza etc. IICT and CCMB are currently targeting different tropical viruses and successfully shutting down the genes. Despite all these caveats, majority of the researchers are working in this fast moving field that have high hope in near future. There is a strong belief that, "RNAi will deliver its therapy promises". (The author is group leader, head, Functional Genomics and Gene Silencing & head, Bio-Safety and Insect Tissue Culture Labs, Centre For Cellular and Molecular Biology, Hyderabad.)

 
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