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Hello, my name is John Rossi,
and I am going to be presenting a
talk on systemic RNA interference
therapeutics for the
treatment of HIV-1 infection.
In particular, I'm
going to be focusing
on two different methodologies that
we have developed over the past two
years for delivering smaller
interfering RNAs, the target
either HIV itself
or host factors that
are necessary for HIV replication.
These are RNA aptamers and
PAMAM flexible dendrimers.
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This next slide
depicts HIV life cycle.
And beginning from the top and
working our way through the middle
of the slide, you can see that
HIV is an envelope virus, which it
interacts with primarily memory
T cells by the CD4 receptor
and one of two different
chemokine receptors,
one called CCR5 and the
other one called CXCR4.
The interaction is via the gp 120
HIV envelope protein, which then
allows the virus to be
internalized into the host cell,
were the viral RNA
is converted to DNA.
The DNA then in its
double stranded form
migrates to the nucleus of the cell.
There it integrates via the HIV
encoded integrase in several host
enzymes into those chromosome.
And then once that
cell is activated,
the HIV LPR, which is
the promoter region,
is used for
transcriptional initiation.
Driving first fully
spliced RNAs that encode
the regulatory proteins tat/rev,
both necessary for early events
in the viral life cycle.
Once the amount of protein
builds up to a sufficient level,
it blocks splicing.
Allowing unspliced messenger
RNAs to traffic for the nucleus
to the cytoplasm.
And then following translation
of the structural proteins,
the gag on M proteins,
and then subsequently
budding of the virus when it
encapsulates the full length
unspliced RNA.