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Review
9.
RNA interference and its therapeutic applications -
T. SrinivasaRao, Ch SrinivasaPrasad, Showkat Ahmed
Shah, Mudasir Ali Rather
Vet World. 2011; 4(5): 225-229
doi:
10.5455/vetworld.2011.225-229
Abstract
RNAi is a potent method, requiring only a few
molecules of dsRNA per cell to silence the
expression. Long molecules of double stranded RNA
(dsRNA) trigger the process. The dsRNA comes from
virus and transposon activity in natural RNAi
process, while it can be injected in the cells in
experimental processes. The strand of the dsRNA
that is identical in sequence to a region in
target mRNA molecule is called the sense strand,
and the other strand which is complimentary is
termed the antisense strand. An enzyme complex
called DICER thought to be similar to RNAase III
then recognizes dsRNA, and cuts it into roughly
22- nucleotide long fragments. These fragments
termed siRNAs for “small interfering RNAs” remain
in double stranded duplexes with very short 3′
overhangs. However, only one of the two strands,
known as the guide strand or antisense strand
binds the argonaute protein of RNA-induced
silencing complex (RISC) and target the
complementary mRNA resulting gene silencing. The
other anti-guide strand or passenger strand is
degraded as a RISC substrate during the process of
RISC activation. This form of RNAi is termed as
post transcriptional gene silencing (PTGS); other
forms are also thought to operate at the genomic
or transcriptional level in some organisms. In
mammals dsRNA longer than 30 base pairs induces a
nonspecific antiviral response. This so-called
interferon response results in a nonspecific
arrest in translation and induction of apoptosis.
This cascade induces a global non-specific
suppression of translation, which in turn triggers
apoptosis. Interestingly, dsRNAs less than 30 nt
in length do not activate the antiviral response
and specifically switched off genes in human cells
without initiating the acute phase response. Thus
these siRNAs are suitable for gene target
validation and therapeutic applications in many
species, including humans.
Keywords: RNAi,
Delivery of siRNA, Therapeutic applications,
Antivirus, Apoptosis, Cell.
