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Systemic RNA interference (RNAi) therapeutics for the treatment of HIV-1

Published on February 4, 2014 Reviewed on July 16, 2020   38 min

A selection of talks on Clinical Practice

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0:00
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.
0:28
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.
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Systemic RNA interference (RNAi) therapeutics for the treatment of HIV-1

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