Re: [DIYbio] Reverse transcriptase induced apoptosis as a possible retroviral treatment

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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--
Nathan McCorkle
Rochester Institute of Technology
College of Science, Biotechnology/Bioinformatics

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