The Nobel Prize in Physiology or Medicine for 2006 is awarded to Andrew
Fire, PhD, of Stanford University School of Medicine, and Craig C. Mello, PhD,
of the University of Massachusetts Medical School, for their discoveries
related to RNA interference.
Fire, Mello and colleagues discovered that certain RNA molecules could be
used to turn off specific genes in animal cells. The silencing process—called
RNA interference, or RNAi — has become a widespread research tool. Their
findings were published in Nature in 1998. In their experiments, the
scientists silenced silence an individual gene in
Caenorhabditis elegans
by injecting a double-stranded version of its messenger RNA. This “RNA
silencing” has since been shown to work in nearly every animal cell.
Here is the abstract of their 1998 paper:
Fire A, Xu SQ,
Montgomery MK, Kostas SA,
Driver SE, Mello CC. 1998
Potent and specific genetic interference by double-stranded RNA in
Caenorhabditis elegans. Nature 391: 806-811.
Abstract: Experimental introduction of RNA
into cells can be used in certain biological systems to interfere with
function of an endogenous gene. Such effects have been proposed io result
from a simple antisense mechanism that depends on hybridization between the
injected RNA and endogenous messenger RNA transcripts, RNA interference has
been used in the nematode Caenorhabditis elegans to manipulate gene
expression. Here we investigate the requirements for structure and delivery
of the interfering RNA. To our surprise, we found that double-stranded RNA
was substantially more effective at producing interference than was either
strand individually. After injection into adult animals, purified single
strands had at most a modest effect, whereas double-stranded mixtures caused
potent and specific interference. The effects of this interference were
evident in bath the injected animals and their progeny. Only a few molecules
of injected double-stranded RNA were required per affected cell, arguing
against stochiometric interference with endogenous mRNA and suggesting that
there could be a catalytic or amplification component in the interference
process.
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