No, he's suggesting using viral reverse transcriptase binding sites to
ensure that his RNA gets reverse transcribed into cDNA, from which
killer genes can be expressed.
The logic is that reverse transcriptase will only be active in cells
with viruses, so the RNA payload will only work in this context. It's
clever!
Just a design note; the RNA would have to be the reverse complement of
the desired cDNA.
This strategy could work with some modification against other RNA
viruses that use a replicase to copy their RNA-only genomes. An mRNA
coding for a killer gene could be introduced, where a low copy number of
mRNA will encode a sub-lethal dose of toxin. If replicase is present to
copy the RNA near exponentially, lethal toxin kicks in.
If you could manage this with something that activates the caspase
cascade, you might be able to destroy the assembled viruses already in
the cell, too.
On 07/02/12 01:04, Nathan McCorkle wrote:
> So you're depending on viral transcription factors? I thought most
> viruses use strong/universal promoters that were basically
> constitutively expressed.
>
> On Sat, Feb 4, 2012 at 5:48 PM, Joshua Dockery <jndockery@gmail.com> wrote:
>> Desired Outcome:
>> - Inoculation of healthy cell populations by selective elimination of
>> infected cells and lysis of manufactured viral products prior to
>> budding.
>>
>> Background / Introduction:
>> - Retroviruses deliver a payload of RNA and enzymes which allow
>> expression of the viral RNA.
>> - Gene therapy is a technique where designer payloads are delivered
>> to cells via a virus called a vector.
>> - Apoptosis is a form of Programmed Cell Death which can be triggered
>> by a number of mechanisms. The cell and all internal proteins are
>> destroyed by a rapidly growing signal cascade where a small
>> introductory signal can quickly be amplified into a cell-wide
>> activation of proteases or other lytic enzymes.
>>
>> Method:
>> - Use gene therapy to deliver RNA containing apoptosis signaling
>> proteins. Use the original viral RNA as a template ensuring
>> engineered RNA has proper promoter regions for uptake by viral
>> expression mechanisms.
>> - Basically: if retroviral proteins are present, destroy self.
>> Otherwise, do nothing.
>>
>> Details:
>> - Viral vector will need to be derived from offending retrovirus
>> ensuring delivery to proper cells.
>> - Signaling enzyme should not require post-translational processing.
>> - Plausible examples: cytochrome c or Bim: http://www.ncbi.nlm.nih.gov/pubmed/21808067
>> - There would be an expression race: would expression of the signal
>> cause a caspase activation cascade more quickly than the retrovirus
>> can replicate and reach sufficient concentration for budding? (My
>> guess would be yes by a longshot: retroviral RNA and engineered RNA
>> should be replicated at the same rate, however only the apoptosis
>> signal would have additional mechanisms of amplification.)
>>
>> Benefits of approach:
>> - Is inert unless in the presence of viral machinery.
>> - By targeting a required function of a retrovirus instead of any
>> particular epitope or binding site, the evolution of resistant strains
>> becomes less probable.
>> - Inoculated healthy cells act as macrophages, engulfing and
>> destroying invading bacteria (admittedly in an undesirable suicide
>> fashion.)
>> - Same method could also be used to target viruses which use RNA-
>> dependent RNA polymerase.
>>
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>
>
>
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