
Scientists make precise edits to mitochondrial DNA for first time - pseudolus
https://www.nature.com/articles/d41586-020-02054-5
======
koeng
I used to be a mitochondrial engineer. This advance is fantastic, and not
surprising. In 2006[0] they showed that you could get zinc fingers (similar to
TALENs, which is what they use in paper) to site-specifically modify things in
mitochondria. For reference, that is about 7 years before CRISPR was
discovered.

Base editors were more recently discovered, so it was only a matter of time
before they figured out how to do it in mitochondria.

I will be surprised if they figure out how to genetically transform
mitochondria robustly (in humans, etc). That research has been going on for
_decades_ , and still hasn't been figured out. One day, it will be, and I'm
looking forward to learning about how they do it. They figured out
transformation of yeast mitochondria in the 80s, still haven't figured out
human mitochondria.

I think it's going to do something with either RNA import + reverse
transcription OR conjugation[1]. I tried RNA import in yeast, and it doesn't
really work, but I think conjugation has real potential, especially now that
they got endosymbiosis of E.coli working[2].

[0]
[https://www.pnas.org/content/103/52/19689](https://www.pnas.org/content/103/52/19689)
[1]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC554353/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC554353/)
[2]
[https://doi.org/10.1073/pnas.1813143115](https://doi.org/10.1073/pnas.1813143115)

~~~
alfiedotwtf
Do you think this is the start of the land rush for gene manipulation
therapies?

~~~
koeng
Yep, pretty much. It’s a very interesting time - genetic therapies have
extremely low marginal cost, but very high capital cost. Unlike software
systems, they can mean life or death. Piracy of genetic therapies will be
really interesting.

Someday we might not just have antivaxers, but “rogue vaxers” who develop
vaccines to diseases that pharma ignore and DIY test themselves.

~~~
haxiomic
We have this today to an extent, here’s someone who tested a DIY gene editing
cure for lactose intolerance on themselves
[https://youtu.be/aoczYXJeMY4](https://youtu.be/aoczYXJeMY4)

(Spoiler: it worked, very well in fact!)

~~~
koeng
Im a bit suspicious of the lactose experiment, mainly because there wasn’t
hard data to back it up. Back then there was a spurt . AFAIK there are two
people who have DIY gene engineered themselves and have actually gotten data
to back it up, but only 1 who is public about it, and it wasn’t a cool
experiment (just showed RNA transcription) so it isn’t even easy to find.

Josiah Zayner pretty much knows everyone who has tried DIY gene injection and
over the last year or so there has actually been a decrease in people trying
it (bit stale from 2019, but here is his presentation at BioHTP
[https://youtu.be/1QOFDpYnEgY?t=4904](https://youtu.be/1QOFDpYnEgY?t=4904))

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vikramkr
There's a host of rare diseases that originate from mtDNA mutations that this
could have applications in. I know the tech/Silicon Valley crowd tends to love
anti-aging stuff as well, so for all y'all into life extension stuff, this
should interest you as well because of mitochondria's hypothesized role in
aging[0].

[0]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779179/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779179/)

~~~
cachestash
I have been taking a high grade CoQ10 supplement.

CoQ10 is the primary antioxidant the human cell provides to protect and
support mitochondria. It helps generate ATP within the mitochondria, the main
energy driver we have.

CoQ10 is ubiquitous and produce within the body, however after the age of 20
levels start to drop, so it makes sense to consider supplements to top levels
up if you're north of 30.

I love the stuff myself. I went from a tired feeling 45 year old with brain
fog, to having a lot more energy and a mind keen to engage all day with
whatever I have going on at work

[https://examine.com/supplements/coenzyme-q10/#effect-
matrix](https://examine.com/supplements/coenzyme-q10/#effect-matrix)

~~~
pengaru
How did you disambiguate these claimed CoQ10 effects from the results of
taping your mouth shut at night?

"Not only did it fix my apnoea [sic] and huge lack of energy during the day"

[https://news.ycombinator.com/item?id=23432440](https://news.ycombinator.com/item?id=23432440)

~~~
LeonB
“apnoea” is the British spelling.

~~~
pengaru
TIL, thanks, I didn't know that.

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fasteo
I suffer from a genetic disease in my mitochondrial DNA (single, large-scale
deletion), so this is great news for me.

I have been closely following mitochondrial research since I was diagnosed 12
years ago, and the progression in our knowledge about mitochondria have been
exponential. Truly impressive.

My sincere appreciation for all researchers out there (even though I do not
expect an actual cure in the foreseeable future; say, next 15 years)

~~~
oehtXRwMkIs
How does the disease impact your life, if I may ask?

~~~
fasteo
Mitochondrial disease is not a disease per se, but I broad category of all
kinds of both nuclear and mitochondrial mutations. Some of them are fatal and
kids die within days or years after birth and some are more like chronic
conditions with a varying degrees of severity.

In my case, my genotype is a single, large-scale mtDNA deletion. It is
heteroplasmic, meaning that some of my mitochondria are normal and some are
mutant. In these type of mutations, heteroplasmy percentage drives disease
severity.

Disease is also progressive. Mutant mitochondria have a replication advantage,
so that the percentage of mutant mitochondria goes up as you age.

My phenotype is called CPEO (Chronic Progressive External Ophthalmoplegia),
probably the most common and benign disease presentation. I have ptosis
(droopy eyelids) and diplopia (double vision). Both corrected by surgery.

I have also some systemic symptoms, mostly a profound "fatigue" that hits me
2-3 days per month. I quote fatigue because it is a unique feeling not like
normal fatigue. Malaise could be also a good definition.

I am lucky. I have a normal life with minor issues. A good diet and exercise
made a huge difference. I also take some over the counter supplements that
also help my body to cope with all the mutant mitochondria.

------
Symmetry
I wonder how you'd distribute these, therapeutically. Our bodies have
mechanisms to let healthier mitochondria out compete less healthy mitochondria
within a cell - the oxidative stress mitochondria are under basically requires
that for us to stay healthy - but how do you get the mitochondria into your
cells. Especially long lived cells like skeletal muscles much less neurons?

~~~
Koshkin
This sounds very complicated. Maybe the future of medicine is in _simplifying_
the human biology and possibly even "upgrading" it to something that is less
susceptible to illness and injury.

~~~
stallmanite
Interesting idea. I wonder if instead of requiring oxygen to hand off
electrons to during respiration we could substitute a simpler system by
dumping the excess charge via a wire? Anyone with domain expertise care to
comment on whether this is possible?

~~~
op03
Electroactive bacteria?

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gwern
Paper mirror:
[https://www.gwern.net/docs/genetics/editing/2020-mok.pdf](https://www.gwern.net/docs/genetics/editing/2020-mok.pdf)

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yters
Could someone create a respiratory virus that spreads throughout the earth's
population gene editing everyone into perfection?

~~~
jacquesm
What could possibly go wrong?

~~~
0xdeadbeefbabe
Or right

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douglaswlance
How long until we can write DNA as easily as we do Python?

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siraben
Reminds me of xkcd's "hottest editors"[0].

In all seriousness, if I'm reading this correctly, Ddd9 would resolve the
challenge of using CRISPR-Cas9 to edit mitochondrial genomes. Could this be
used for treatments of mitochondrial diseases in the future? Additionally,
mitochondrial DNA is passed through the mother, so modification could
potentially have a long lasting effect.

[0] [https://xkcd.com/1823/](https://xkcd.com/1823/)

~~~
checker659
I think an electron app will beat both Vim and Emacs to it.

~~~
TomMarius
I would even happily suffer through Electron in this rare case

