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Abstract: Small interference RNA (si RNA) is a
promising therapeutic module which is making a big news
due to its safe & efficus mode of action. SiRNA is
offering better therapeutic interventions in the areas
like AIDS, hepatitis, cancer, Hypertension etc. Its mode
of action involves the blockade of protein synthesis
which does not harm the treated organ but prevents key
proteins mediating pathogenesis of the disease. There
are products available for the treatment of age related
macular degenerative disease for prevention of loss of
vision. Here it is going to halt the production of a key
pathogenic protein vegus (vascular endothelial growth
factor). Many of the products are under various stages
of clinical trial. There is a break through in medicine
&therapeutics which is truly a biotechnological
intervention.
Background
The first hints of the existence of the gene silencing
mechanism that is now called RNA interference emerged
from work on the genetic modification of plants in the
late 1980s. Attempts to deepen the violet hue of
petunias by expressing higher levels of an enzyme
involved in the synthesis of the pigment unexpectedly of
extra copies of the gene had somehow caused a decrease
in its expression rather than the anticipated increase.
For some time this remained an unexplained oddity. It
was soon joined by similar observations in the
filamentous fungus Neurospora crassa and then the
nematode worm Caenorhabditis elegans. Once the large
community of developmental biologists working on the
worm became involved, the pace quickened. In 1998 the
key observation was made that led to the coining of term
“RNA interference”. Fire and Mello showed that double
standard RNA (mRNA) with sequence complementary to the
antisense strand for which they won Nobel prize in
medicine in 2006.
Introduction
RNA interference or gene silencing is a phenomenon by
which the double stranded RNAs mediated through siRNAs,
elicit degradation of target mRNA containing homologous
sequences thereby inhibiting the protein synthesis, in
effect silencing the gene responsible for the same. Ease
of application, cost effectiveness and possibilities for
genome wide reverse genetics have quickly turned the
approach into a widely accepted one. RNAi has been
described in several eukaryotics organisms, both
unicellular (Trypanosoma brucei) and multicellular (Caenorhabditis
elegans, Drosophila melanogaster, planaria, hydra,
plants, zebra fis, mice and humans). Transfection of
dsRNA into animal cell results in the potent, long
lasting, (typically several days) posttranscriptional
silencing of homologous genes. As somatic mammalian
cells exhibit an innate immune response (responding with
interferon mediated defenses) when exposed to dsRNAs
with more than 30bp, there was an initial confusion due
to vigorous non specific shut down of transcription and
translation, partly due to the activation of RNA
dependent protein kinase activity (PKR). Later on
studies proved that small interfering RNAs (siRNA) with
19-23 nucleotides length, work efficiently in silencing
the gene. It is a robust method for lowering specific
protein levels compared to traditional techniques such
as antisense, ribozymes or microinjection of function
blocking antibodies.
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