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Hi. My name is John Rossi.
I'm a professor at City of Hope National
Medical Center in Los Angeles, California.
Today's presentation is about
small interfering RNAs or siRNAs,
their mechanism of action and
development as human therapeutics.
Co-presenting with me
today is Daniel Rossi,
a Clinical Project Associate
at Duet BioTherapeutics.
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Small interfering RNAs,
known commonly as siRNAs,
are small strands of RNA which can
completely alter the expression of genes
through a process known as
RNA interference or RNAi.
This is a process by which double
stranded RNA molecules produce
sequence-specific suppression
of gene expression
via translational or
transcriptional repression.
The end result being the
suppression of a given protein.
It's thought to have originally
evolved as a defense mechanism
against the invasion
of exogenous genes,
such as those from viruses,
making its original purpose something
akin to an intracellular immune system.
In a biologist's hands,
it offers a powerful research tool and method
to treat currently undruggable diseases,
allowing the suppression
of proteins
which have yet evaded effective inhibition
by traditional pharmaceutical drugs.
In particular, it shows
great promise in genetic diseases,
infectious diseases, and cancer.
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Now, for a quick primer on
how siRNA functions at the
level of molecular biology.
The production of siRNA to
achieve gene silencing,
begins with long
double stranded RNAs
formed from a hairpin or
from complementary RNAs,
which are cleaved by an
endoribonuclease called Dicer,
which cuts the long double
stranded RNA molecule to
form small interfering
RNA, or siRNA.
This shorter strand of RNA is
capable of getting
incorporated with
a number of proteins
to form the RNA
induced silencing
complex or RISC,
where the strand
is unwound to form
a single stranded siRNA
with the strand less
thermodynamically stable
at the five prime end
chosen to remain
part of the complex.
This single siRNA
strand can now guide
the RISC to its
complementary mRNA target.
Once RISC binds to its target
and induces mRNA cleavage,
the cut mRNA strand
will be degraded,
and in turn, will never be able
to be translated into protein.
