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Knockout of FOXL2 In Vivo?
A paper was published a few years ago (https://cell.com/fulltext/S0092-8674%2809%2901433-0) detailing a study where adult ovaries were transformed into testes via ablation of FOXL2 in mice.
I'm trans-masc and nonbinary, I have been dealing with extreme gender dysphoria my whole life. Hence, my motivation to knock out FOXL2.
My idea is to use SpCas9-HF1 to Knockout FOXL2 by creating nano-particles of the cas9 and gRNA in chitosan (chitosan has been shown to be a potential vector https://ncbi.nlm.nih.gov/pmc/articles/PMC4717060/?fbclid=IwAR0K7C8GounA9DZwkIRm8qSGMSKuo_uHsl8-2qd2fGjnIgn5SkPXddcODsY, although it is not as effective as AAV), then inject them into the blood stream.
Assuming I can source all the material, how likely is this to work?
Comments
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From my recollection of this research, the reagent had to be injected directly into the ovaries to work. Assuming that this even works in humans the same way it does in mice, the biggest problem for a DIY attempt would probably be getting a big enough needle to reach the ovaries, and then having really good aim.
I'm sure a surgeon or a gynecologist could manage maybe with some additional diagnostics, but given how small human ovaries are compared to the human abdomen, I'd imagine it wouldn't be possible for most people.
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Tekniklr, do you recall the article where is states the therapy has be be injected directly in the ovaries?
Can I inject the therapy in a vein every day over a few weeks? This way the nano-particles reach all cells, including the ovaries?
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Unfortunately, this is from my (possibly faulty) recollection of a discussion about this a few years back in our community Slack (you can join from the slack link on the biohack.me home page) and that discussion has long since disappeared from the history our tier of Slack provides.
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Ahh, that's alright.
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Based off this conversation and your other posts, you really should think about developing some skills sets before you aim for the ovaries. Despite, the hype, biology remains a bit more difficult that smacking a new battery in a phone.
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@glims okay, I've done some of the kits from Amino Labs, like bacteria transformations and extracting engineered proteins. What other experiments should I do to develop skills?
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New plan: Incasing the gene therapy in Fe3O4, that way it will act as a magnetic nano-particle, so I can inject it into a vein and then use magnets to direct the therapy to the ovaries. Thoughts?
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That sounds incredible over complicated. If memory doesn't cheat me the guiding was far more complicated than expected. The tool you use to see what is going on in your body is going to interfere with the guidance system the nanobots have.
I didn't look into genetic modification too much, but do you really need to modify just a single gene for the wanted effect? Are you sure there are not going to be secondary effects on other organs?
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Dang it . . . quantum dots also sounds like promising way to guide the gene therapy, but I don't understand it :p. I'll keep thinking of a better guiding technique.
"The tool you use to see what is going on in your body . . . " -- Can you elaborate on this? What exact tool are you referring too?
"do you really need to modify just a single gene for the wanted effect?" -- Yes, because FOXL2 and DMRT1 are master-regulatory genes, as in they effect the transcription of a lot of other genes.
But there is a catch, the study did not knockout FOXL2, rather an "ablation". Ergo, they modified the mice as embryos such that when they are under an aromatase-inhibitor, FOXL2 will lose it's function. (From my understanding at least).
I have not read a study that used gene therapy to knockout FOXL2. That being said, I doubt a knockout of FOXL2 would have no effect on ovarian function because ablation and knockout both have the same effect of inhibition of FOXL2.
"Are you sure there are not going to be secondary effects on other organs?" -- Not sure, but probably not because many folks go on hrt with no organ damage.
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"The tool you use to see what is going on in your body . . . " -- Can you elaborate on this? What exact tool are you referring too?
The tools, or medical instrument, use electromagnetic fields or sounds too tell you where the nanotech is ( is still in the stomach ? move to the intestine? etc... ). Example the electromagnetic field to locate nanotech could interfere with the communication and guidance of the nanotechnology. That was the biggest problem last time I looked into it.
nanotech is too small for an antenna or Bluetooth and they are at best of time unstable.
The how to see what happens in the body with out messing with the tech in the body is the problem.
"Are you sure there are not going to be secondary effects on other organs?" -- Not sure, but probably not because many folks go on hrt with no organ damage.
Not an expert in genetics or hormones , but aren't this 2 very different approaches. And have 2 very different side effects. I don't think you can use the side effect suffered from people during hrt and expect similar result with gene alterations.
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Probably wont be secondary effects on organs from an alteration to their master regulatory genes because 'people take hrt'..... dafuq?
I eat oranges. Doesn't mean I should try replacing my left nut with a kumquat. And I would sound pretty confused if I just conflated the two things, right?
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I think this is one reason why the treatment in mice was targeted directly at the ovaries, to prevent any other systemic effects.
But, you also don’t know what the mices’ experience with this was either, because testes want to be cooler than ovaries, maybe the mice felt discomfort because their “balls” were too warm and can never drop? Mice can’t report such things, so we can only measure one subset of possible effects they experienced, basically that they didn’t die and started producing testosterone instead of estrogen.
Sure, we have good evidence of what switching to testosterone from estrogen in humans does, but we can’t assume nothing else additionally happened that the researchers were unwilling or unable to measure.
