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I was at a talk by Dr. Jeremy Reiter from UCSF where he identified a repurposing of the cell cycle by the progenitors of multiciliated cells to induce centriole replication followed by basal body formation, then followed by migration into the cell membrane to form cilia.
Curiously, the manner by which these cells are able to enter this cell cycle does not appear to be the result of new machinery that arises but due to the suppression of DNA synthesis machinery that appears to be required for regular cell cycle division by the expression of E2F7. These cells undergo one and a half cell cycles and then end their cycles and cease division, with this one and a half special cycle contributing to specialization across various stages of the cilia development corresponding to the phenotypes listed above. E2F7 knockout alone appears sufficient to abrogate the special cell cycle, and E2F7 appears sufficient alone to prevent DNA synthesis.
This raised a question naturally for me, which is- what happens when you artificially overexpress E2F7? Does this cause cell cycle arrest, or does it lead to DNA synthesis arrest and cell death for proliferating cells that attempt to divide without completing DNA replication?
I suggested that it would be interesting to try an E2F7 mRNA therapeutic targeted to cancer cells to see if it could function as a âcleanâ chemotherapy that specifically targets quickly dividing tumors, while solving on its own the problem with most chemotherapies which is that they are carcinogenic in themselves and extraneously toxic to the human body compared to something that could reprogram endogenously that is innately biocompatible.
He concurred that this is a very interesting experiment and noted they hadnât thought to try it. Iâm excited to see what happens next! He did note that his lab doesnât do translational medicine though, so hopefully this research angle doesnât vanish.
I found one paper where E2F7 was used to reduce liver tumor growth in mice, but I donât think that paperâs authors knew how universally applicable that might be- and importantly that paper indicated that genetic integrity in affected cells dropped- suggesting forced division and cell death from DNA synthesis suppression.
Just a bit of scientific information to ponder in the lens of biohacking. None of this is relevant to any sort of product (and you shouldn't be putting E2F7 mRNA into yourselves), but the more everyone knows, the better for all of us.
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