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RNAi Technology
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Over the last few years,
clinical pharmacology has been undergoing an enormous transformation, due to
incorporation of the latest advances in the field of Molecular Biology to the
development of new medicaments.
Biochemical signalling plays a
critical role in cellular function, controlling both normal cell growth and
appearance of different alterations involved in the development of diverse
pathologies. There are a great number of pathologies, which appear because of
the abnormal activity of a specific protein. In these cases, the treatment of
these pathologies would be based on suppressing this activity.
A new technology called RNA
interference (RNAi) has been recently discovered. RNAi produces specific gene
silencing via small double stranded molecules of RNA. Put more simply, an
individual’s genetic information is recorded in his DNA and is organized in
genes. In the cell nucleus these genes transcribe genetic information
contained in their DNA into messenger RNA (mRNA). This mRNA leaves the
nucleus and interacts with a ribosome, which translates the mRNA sequence
into its corresponding protein/enzyme. This protein translation and synthesis
may be blocked by acting on the mRNA, which is what RNA interference does.
RNA interference is a
gene-specific post-transcriptional silencing mechanism where small RNA
molecules which are complementary to a mRNA direct its degradation, therefore
avoiding its translation into proteins.
Gene silencing via RNA
interference is induced by small double stranded RNA molecules of between 21
and 27 nucleotides called siRNA (small interfering RNA). These siRNA suffer a
series of processing rounds within the cell and as a consequence their
double-stranded structure is separated into a sense strand and an antisense
strand. The antisense strand hybridizes specifically to the mRNA by
base-pairing, and the resulting complex is recognised by cellular mechanisms
and degraded. Each siRNA is highly specific for the target nucleotide
sequence it degrades. This phenomenon of gene interference occurs naturally
within the organism, and is involved in development and defence against
virus.
However, siRNAs may also be
introduced artificially into an organism so as to silence a specific gene.
Any gene with a known sequence can be the target for a siRNA designed to
contain the complementary sequence to said gene. As such, siRNAs constitute a
highly valuable tool for the study of gene function, therapeutic target
validation, for the analysis of mechanisms of action of different
medicaments, or as a therapy against diseases of genetic origin.
RNAi is a potent tool which is
undergoing a grand development with therapeutic ends, due mainly to two
facts: all cells contain the necessary machinery to perform RNA interference
and all genes are potential targets. This technology has certain advantages
when compared to different types of therapies, including a rational design
based on the knowledge of the therapeutic target on which one wishes to act,
high specificity and reduced secondary effects. Sylentis applies this RNAi
technology to find molecules with therapeutic potential against different
diseases. Said technology is applied by two different methods: via small
interfering RNA fragments (siRNA) and via hairpin RNA (shRNA). These
molecules allow the specific silencing of messenger RNAs which translate
proteins responsible for alterations or non-desired effects within the cell,
therefore inhibiting their effects. Sylentis has developed proprietary
SIRFINDER™ technology, which allows us to design siRNAs with pharmacological
potential, based on an optimized search of the most adequate sequences, which
includes the use of bioinformatic tools, reducing research times and
maximising results. Various siRNA molecules developed using this technology,
have proven active against different therapeutic targets.
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Posted by : Deepak Kumar