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MicroRNA gets down to business
http://www.nature.com/naturebiotechnology
George S MackDrugs targeting microRNAs lie some way off, but diagnostics look promising and commercial interest is growing.
The 1993 discovery of a gene expressing small non-protein-coding RNAs in
Caenorhabditis elegans wasnt thought of as a particularly momentous event1. But in unearthing that piece of information, Victor Ambros, then of Harvard University, ushered in a new age of research that would lead to the discovery and study of a previously unknown class of endogenous, single-stranded, 19- to 21-nucleotide molecules called microRNAs (miRNAs) that regulate as much as 30% of mammalian genes (Fig. 1).
Today it is predicted that humans express thousands of miRNAs, but up to now just a few more or less than 500 have been described. These miRNAs inhibit messenger RNAs (mRNAs) and prevent translation of anywhere from tens to hundreds of messages at a time. With that kind of wide-ranging influence, its not surprising that they are found to be deregulated in many diseases. Because evolution has conserved these miRNAs and enabled them to multitask, researchers are wondering if science is on the edge of a sweeping revolution in which control of a few small molecules could create cascading effects of major importance in complex disease situations. But whereas a few companies have jumped into the miRNA fieldmost as suppliers of tools and information (Table 1)the biotech industry seems to be awaiting more information on mechanism and some clarity on the intellectual property (IP) situation. Who then will do the research and when will it get into the clinic?
The Holy Grail
Controlling RNA transcription and translation has long been eyed as the Holy Grail of molecular biology. The basic goal of any RNA regulator, from antisense to RNA interference (RNAi) and beyond, is to find small
complementary oligonucleotides and get them inside a cell so they can bind to a segment of mRNA, prevent translation or initiate cleavage and thereby interrupt protein synthesis. Now with the discovery of miRNAs, researchers are uncovering a natural form of post-transcriptional interference, which could be fertile ground for advancements in medicine. But unlike the better known RNAi, which is accomplished with double-stranded short-interfering RNA (siRNA) that knocks down a single gene (Table...