The Nobel Prize in Medicine or Physiology was recently awarded to Craig Mello, Ph.D, Professor of Molecular Medicine at the University of Massachusetts Medical School and Andrew Fire, Ph.D, Professor at the Department of Pathology and Genetics at Stanford University Medical School for their discovery of the mechanism of RNA interference.
The Nobel committee announced its recognition of this discovery eight years after it was first published in Nature. Mello and Fire were doing research together, exploring gene expression in C. elegans, or nematode worms, when they uncovered the action of RNA interference.
RNA interference, or RNAi, is a process used to downplay the effects of a particular gene. According to the basic central biology dogma, genes are responsible for coding for mRNA. mRNA, in turn, is translated into the proteins that are necessary for our biological processes.
The action of RNAi comes in at the mRNA level. If particular sequences of double-stranded sections of RNA (dsRNA) are introduced into the cell, they can separate and attach themselves to the transcripted mRNA at the appropriate complementary sections by base-pairing and thus interfere with the processes of the cell. This attachment of RNAi cleaves and destroys the bound mRNA, thus silencing or knocking-down the gene and its subsequent protein.
Michael Hadjiargyrou, Ph.D, Professor of Biomedical Engineering, Genetics and Orthopaedics at Stony Brook University, explains, ‘[the] impact of the RNAi technology is tremendous’ because its discovery is germane ‘more at the basic science level.’ It has many potential applications in both the clinical and experimental setting.
The development of this technology is fundamental to its relevant science and medical fields. Gene knockdown, for example, can be, one day, used to treat Cancer patients, according to Dr. Hadjiargyrou. If a gene is known to be implicated in producing malignant, cancerous cells, it can be ‘knocked-down’ using RNAi methods and effectively silenced. If the gene’s activity is silenced or diminished, tumor growth in the patient may be slowed or even halted.
RNAi would be an effective tool for studying the development of organisms. By silencing one gene, for example, the compensatory actions of other genes in its locus, or family of genes, during embryological development can be studied in detail.
‘This technology has really revolutionized experimental biology,’ says Greg Hannon, Ph.D, Professor at Cold Spring Harbor Labs and Howard Hughes Medical Investigator. ‘It has had an impact on people working in nearly every field and in organisms ranging from planaria to mammals,’ he continues. The tremendous impression RNAi has had on biological research is evidenced by the fact that scientists ‘can do things today that we would not have dreamed to be possible only about 5 years ago,’ according to Dr. Hannon.
The potential clinical applications of RNAi technology have yet to be confirmed. In fact, its full impact on the medical and experimental biological fields has not been realized. Some experts suggest that the acknowledgment of the discovery of RNAi came too quickly, without enough proof to dislodge the hype that RNAi has created. Usually the Nobel prize comes decades after an initial discovery.
Dr. Hannon explains that although ‘we are not yet completely sure whether RNAi will be the drug of the future, its impact on biology is already abundantly clear.’ Hannon suggests that it was only a matter of time. RNAi being not only classified as a technology, but also as a ‘fundamental biological process’ is deserving of recognition even without its ‘potential impact on human health.’
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