phriendlyphellow

phriendlyphellow t1_iy2hqay wrote

There are two ways the cell can fix the double stranded break (DSB): Non-homologous End Joining (NHEJ), which is sloppy, and Homology Directed DNA Repair (HDR), which is cleaner but limited to two stages of the cell cycle.

This article describes the challenge.

“Given that HDR is restricted to the S and G2 phases of the cell cycle, only present in dividing cells, this approach might not be suitable for editing and repairing the genome in non-dividing cells.”

Here is the original paper that the above website sites as a source.

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phriendlyphellow t1_ivpyn4r wrote

And to your point about gene therapy…

This is a hot area of synthetic regenerative biology. Instead of dealing with donor matching and immunosuppression, what if you could extract a patient’s cells, reprogram them to a pluri- or multi- potent state, use gene editing tools like CRISPR to correct any degenerative genetic defect, grow the patients pool of cells, infuse them into a decellularized extracellular matrix (ECM) of an organ they need, and cisplant (as opposed to transplant, because it’s their own cells).

Theoretically possible and a number of these techniques have made it past the proof of concept stage.

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phriendlyphellow t1_ivpxpw9 wrote

We don’t fully understand the mechanism of horizontal gene transfer (HT). If there is HT between host and donor, it would like be transposable elements. And we don’t really understand how genetic information not only escapes the nucleus and cellular membrane of one cell, then transports through the extracullular matrix (ECM) (or vasculature?) to another cell, penetrates the cell membrane, and then navigates to the nucleus, and embeds itself in the other-origin cell… all without being degraded by nucleases that are designed to prevent free-floating nucleic acids (RNA and DNA). 🤷

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phriendlyphellow t1_ivpwr4n wrote

The immunosuppressants simply limit the host’s immune system from attacking the foreign/donor cells/tissues/organs. In fact, the host’s body will, under immunosuppression, do everything it can to keep the vital organ alive. This is why people can continue to live longer and healthily after transplants.

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phriendlyphellow t1_ivpw5d6 wrote

“How can they change anyway?”

All DNA in every cell is subject to “random” mutations over time as cells replicate. DNA damage from radiation and/or oxidative stress causes the changes. Very rarely, there is an accepted mismatch in replication.

To your other point. Horizontal gene transfer is not a whole genome switch, but a rare event of a transposable element arising in a different species. Horizontal transfer of transposable elements is poorly understood and the underlying mechanisms are still largely unknown. You can read more in this 2020 paper. https://www.nature.com/articles/s41467-020-15149-4?error=cookies_not_supported&code=5df6700e-6c24-40ba-9192-85e2acb0d513

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