DMRT1 inhibition?
  • A long time ago I read this story -- http://blogs.discovermagazine.com/notrocketscience/2011/07/20/one-gene-keeps-mickey-from-turning-into-minnie/#.WRXzMca1uMo -- and was kind of curious about whether there were ways to inhibit DMRT1 expression for an adult human, say, myself >_>. Its more hypothetical than practical, since I don't even know where to start suppressing a gene or its activity in an adult human, but - IF there were a way to do something like that it seems like it could save me (and other trans folk) a lot of time and trouble (or make me really sick and have terrible health complications in some way... hopefully not). Obviously if it worked well I wouldn't be fertile or anything, but it could mean an end to taking hormone pills my whole life...
    It looks like in mice this was achieved using, well, tamoxifen inducible cre transgenic mice  + tamoxifen, but I really don't understand cre/lox recombination.. found a wiki on it here that gives me a few clues. https://en.wikipedia.org/wiki/Cre-Lox_recombination . But I really don't know the subject matter well enough to tell yet if they're talking about using the enzyme or whatever to do gene splicing on the embryo or whether it can be done during an animals lifetime (or how that might interact with immunology, etc).
    --update -- reading up on the cre-lox process here https://www.jax.org/news-and-insights/jax-blog/2011/september/cre-lox-breeding-for-dummies seems to indicate that its usually done to the parent, and then the kids have the modified genes. Foo;P
    Just.. theoretical biohacking here, I'm not crazy enough to try this (I don't think). Unless I was able to do it to a mouse, but I'd kind of feel crappy about doing that to a mouse, even, and I have a pet snake, so I'm not all that nice to mice.... just, wishful thinking + curiousity mostly

  • So I tried to think about genetic engineering stuff with both my 'crazy' and 'pragmatic' hats on at the same time yesterday, and came to the conclusion that I should start small. That would give me time to get up to speed both on good science and journaling and stuff, and on chemistry and biochem stuff, get good at handling things appropriately, and so on. I found a diy crispr kit online for about $150 that lets you modify a gene in a bacterium to let it live on another surface than it normally would
  • I dont't think there is any chance to do it in vivo yet.
    Especialy in humans. But maybe in the next couple of decades.
  • The result you are hoping for in this case is external testis that produce female hormones? That may not be too ideal for many transwomen, just physically speaking...
    If you're looking to cut back on the amount of meds you're taking, you could always go for SRS or Orchi, or if you're not too into surgery and have giant piles of money to throw at your hormone situation (or if the health coverage gods smile upon you), switching whatever AA you're on to lupron is basically better in every way other than it costing several thousand dollars per injection...

    I guess I also wonder, how would you know your levels would be where you want them to be after doing this? Would you expect cyclical or static levels? Maybe after this was done on a person, blood tests come back and you just end up taking half as much of whatever meds you are already taking, and still needing to take that forever to maintain fully normal levels, or whatever kind of levels you want. Taking lots of meds forever definitely is kind of sad, but at least having control over your levels is a bit of a perk.

    I don't really know how it would go one way or the other, or how feasible such a thing would be. It's an interesting question for sure, but benefits/limitations/risks/price balance could be unfavorable. In vivo trials of anything CRISPR on humans is still probably a while away, so at least there's plenty of time to think it over.
  • Yeah. Well and a lot of these genes seem closely tied to tumorigenesis. AND my knowledge of chemistry still hasn't advanced past 101 from college way back so.. I would at least need to learn a LOT more than I know to experiment. Plus I've got a surgeon already lined up. I just worry about messing up and having a better option come along in the next five-ten years XD
  • I did manage to get myself added to a 'database' of possible subjects for clonal tissue research, for grafting in clonal tissue, at some but I don't know if that was real or the person calling me when I inquired about their research was shining me on. It was years ago and I've heard nothing since, so.
  • re surgery - I am lined up for it. I just gotta get to where I qualify. Weight loss is a big blocker for me to qualify but I am working on it. I'm tall so my weight is not as much as it sounds and mostly healthy but I still carry a lot of weight - my bloodwork is great, I am starting to keep up in muay thai, so physically I am somewhat healthy, but I've got like 47% bodyfat, which is way too high, and I'm trying to get down to somewhere in the 30% range. So I'm trying to do some lifestyle changes, I've been working on eliminating simple carbs and stuff like that. There's a lot of hacky things I can look at for weight loss I suppose. But I'd rather not gain it all back after. The biggest thing probably being getting enough high quality sleep and cutting out simple carbs aggressively / entirely.  re 'testis that produce female hormones' - in the mice, anyhow, the testis /became/ ovaries, at least structurally and in terms of what genes are active - but not fertile as far as I recall. but I might have read the descriptions wrong. I am unclear how flexible adult tissue'd be. I wonder in the very distant future about reverting some tissue back to stem cells and then moving it forward again. Or doing something like that externally with clonal tissue and then grafting it.
  • So, I emailed Brian Hanley at Butterfly Sciences (the guy who famously did an anti-senescence / mitochondrial energy production related gene hack on himself that may have raised his HGRH levels) just to see whether he'd recommend any resources for DIY gene therapy self-education, and his opinions seemed to be, basically, get a real degree if you're interested in this area, and don't attempt any kind of gene modification like I did, period. And its like, I am already working on software dev stuff, I don't have time / energy / bandwidth to be pursuing anything like that on the side (well, I feel like I do sometimes, but I have severe episodic depression: I just /can't/ half the time, so unless I could work at my own pace...). So, thinking, maybe I can put together a curriculum for self-study from publicly available bluesheets and stuff from diybio groups and whatever. Convinced at this point I will qualify for surgery long before I'll be able to hack my own genes in this respect, but it could be an interesting area to study regardless. Maybe I can hack age-related genes instead, and then survive until much better technologies for transition related stuff become available (or at least long enough to convince people that they're a worthy area to pursue; that a real problem exists which needs to get fixed). He did point me towards an interesting pop-article / public letter  he addressed to anthony atal re: clonal tissue underscoring the issue of the importance of developing a better transition process, which I thought was super cool. https://ieet.org/index.php/IEET2/more/hanley20151111