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The Nobel Prize For Medicine, 2006 - RNAi & C. elegans
Tread Softly Upon
It has been said that most revolutionizing concepts begin with a simple and fundamental observation. Things that go unnoticed by most people. An apple falling out of a tree would never be a cause of concern except to Newton who questioned why it fell down instead of going up. And just like that, we have our laws of gravity.
The roundworm Caenorhabditis elegans lives in soil, where it feeds mainly on bacteria. The humble worm made history in 1998 for being the first multicellular organism to have its genome completely sequenced. This was followed shortly in 2002 with the worm making headlines when three scientists Sydney Brenner of Berkeley, California, John E. Sulston of Cambridge, England, and H. Robert Horvitz of Cambridge, Massachusetts received the Nobel Prize in Physiology or Medicine for their work in understanding genetic regulation of organ development and programmed cell death. Early this week the nematode climbed into the spotlight for yet another time when Andrew Z. Fire of Stanford University and Craig P. Mello of the University of Massachusetts received the Nobel Prize in Physiology or Medicine for their ground breaking research in gene silencing through RNA interference.
When Fire and Mello observed that injecting double stranded RNA into worms resulted in silencing of the gene that matched the genetic code carried by the RNA, they realized that they had discovered a mechanism for genetic regulation. The phenomenon named RNA interference or RNAi results in degradation of mRNA molecules which prevent the protein from being encoded and thus causing the corresponding gene to be silenced. Fire and Mello published their pioneering research in Nature in 1998.
What became apparent subsequently was that RNAi played an enormous role in all organisms regulating gene expression by blocking certain proteins from being encoded and silencing genes, thus controlling cellular functions. The hallmark of this research was not only the importance of the individual discovery, but the overwhelming breadth of their accomplishment.
RNAi has opened the portal for novel genetic technology in a wide variety of organisms, from understanding the function of unknown genes to myriad clinical applications by silencing undesirable genetic function in several diseases. RNAi is being used widely for the study of many genes and has paved the way for novel biomedical applications that hold exciting possibilities.
The Nobel Prize For Medicine, 2006 - RNAi & C. elegans
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Sujatha
URL
October 4, 2006
01:38 PM
M, thanks for this. Do you know if the RNAi thing works even after a person has become sick with a disease or will the interference need to be done when people are babies, based on their genetic predilictions for certain diseases?
i.e., is RNAi a cure for disease or is it a preemptive measure?
M (Tread Softly Upon)
URL
October 4, 2006
02:24 PM
Normally, when a gene is "read" by a cell, the DNA is transcribed into mRNA which travels outside the cell nucleus to be translated into a functioning protein. What RNAi does is it stops a targeted protein from being made and thus preventing a gene from being expressed. Which means that it can be used even after a person has a particular disease. It can silence viruses, cancer producing genes, mutant proteins. You can read more about RNAi in therapeutics here.
You must realize that it is an emerging field and only time can tell where this novel technique will take us.
Sunil
URL
October 4, 2006
08:13 PM
Sujatha.....RNAi has now become very widely used in research labs, and works rather well at the cell culture level, and even in mice (we use it routinely to "knock-down" the mRNA of the protein of our choice, so that that particular protein is not made, and will not function). But it's a long way yet from being actually used in humans to treat disease. But, like M said....it certainly will work in adults.
As far as "doing something as a preemptive measure" goes....a person may have a genetic tendency towards a certain disease......lets take an example of diabetes, where the insulin receptor is defective. Now a gene-therapy approach to that would be to introduce a fully functional insulin-receptor in that person. But again, you wouldn't do that because a person *might* get that disease, you would want to do that only after the person gets the disease. But if you know a baby is going to be born WITH the disease, then you would want to intervene early and try to fix that.
this is getting to be a rather long comment :-)
Sujatha
URL
October 4, 2006
10:25 PM
Thanks M and Sunil. That's what I wanted to know. Don't know much about genetics ("don't know much about biology, don't know much about hissstory..." :))), but it makes me happy to know that the intervention can happen after a person has become sick. Preemptive measures run the risk of targeting people who might never fall sick as Sunil mentioned.
Long comments are good Sunil. Thanks. :)
Sanjay
October 4, 2006
11:14 PM
The problem with RNAi is that the sRNAs can't get into the cells, because they'll react and be degraded on the way there. So the key to RNAi is in delivery methods.
Check out newer approaches like this:
http://www.technologyreview.com/read_article.aspx?id=17578&ch=nanotech
Better delivery vectors have to be found, in order to get sRNAs into the target cells. That's the basic pre-requisite here.
Dr. Jagmohan Kudappa
URL
October 5, 2006
04:47 AM
RNA never synthesise with DNA. So some problem will create when cell devides into two parts. To apply this therapy will create problem in human body. So this system never be successful.
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