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

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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