RNA Interference

It seems like RNA interference might be an opportunity to modfy ourselves in easy and more predictable way (compared to actually genetically modifying ourselves), and I wonder if we should start a project or two around that? For those of you who don't already know, here's the short version of how it works.

If RNA is introduced to the cell which is complementary to messenger RNA, then the resulting double stranded RNA will be destroyed by the cell, which assumes all dsRNA is viral. The fragments of these sequences then continue to bind to more messenger RNA, silencing the expression of that gene for as long as they are present in the cell.

This complementary RNA should be pretty easy to produce and purify in a bacterial vector, if we run a column using a polyA tag (aka the one normally present in mRNA), since naturally occuring sequences don't usually have a bunch of T at one end.

My first idea for a use is (along with a postgrad friend of mine) to knock out a pigment in the iris in order to change eye colour, though that would depend on the turnover rate of pigment there, but other suggestions are welcome. So, advice? Support? Reasons why it's doomed to fail?



  • Did someone say biology!?
    Ok, iris pigmentation is mostly based on structural differences, so that particular idea isn't going to float so well.
    there is a ton of literature about using RNAi to alter enzymatic systems. This is great for upregulating or downregulating certain genes of interest.
    But, as mammals, we have some systems that kinda mess with this clean little concept  so it would actually be better if you used siRNA. This triggers RNAi and then you still have your system in place.

    All the normal biological issues apply here. Poor targeting coupled with a difficulty to apply it to a broad system. Systems backlash where you ended up triggering another pathway that really borks things up.

    That being said, I like the idea. It's got some clinical trials behind it and it's been proven to work some of the time. Plasmids are fairly cheap compared to many things in bio work. 

    I can discuss more about this once you come up with a gene of interest. Each one is different and carries its own roadblocks and issues.

  • Yeah, I was pretty disappointed when I learned how much of eye colour is based on structure rather than pigments. There are still some pigment genes that we could target, mainly melanin depending on which eye colour you have (mine are mostly hazel, so I'm not sure what I could do).

    The reason I was thinking eye colour (aside from cosmetic reasons) is that blocking pigment production is reasonably straightforward compared to altering enzymeatic systems (where there's usually some backlash, as you said) and that it would be very obious if the technique works. I'm happy to work on something else though, if we decide that it's not a viable option.

    So, can anyone think of a gene that they'd like to target?

  • can tetrachromacy be done with RNA? SWS1.

    also any of these for gene doping:
    ACE I
    ACE D
    These might be fun for taste, night vision, and scent:

    No idea how viable, just throwing out ideas here.
  • Sorry, university is quite effective at making me disappear for months at a time. I'm intrigued as to why you happen to have had that list already on hand, but perhaps it's fair enough around here.

    Some of those could make viable targets, I suppose it's a question of which ones have a straightforward enough role in their respective pathways as far as picking targets goes. I was going to say that there's no way tetrachromacy could be done this way since humans don't have the necessary genes for this to work on, but then I researched SWS1 (and the rest of them a while ago) and now I'm not so sure, though it apparently also affects DNA recombination?

    Also perhaps a good idea to think about delivery methods. Liposomes are potentially useful as they're very cheap to make (just sonicate a mixture of our RNA and some phospholipids that aren't going to cause apoptosis) and can just be administered orally. Their main drawback is how randomly they seem to fuse with cells, though this can be improved by targetting them with appropriate antibodies (which would unfortunately increase cost and immunogenicity, we can't have everything). They're probably best suited to a mod where integration into a low percentage of cells throughout the body will still have a noticeable effect.

    Or a viral vector could be used for something a little more potent, but that's probably a bit more than I'm currently capable of in terms of hardware. I'm not really looking to set up a lab since I'm moving country a few times over the coming months, but perhaps someone else is.

    So, perhaps we should pick a target gene based on what methods are available to us? Or something other than RNA interference might be a better focus for now (since liposomes work very well for transient introduction of foreign genes via episomes).


    Sorry about the long post with lack of any real progress, but it certainly is good to be back.

  • Hi there, I would like to say that I am very interested in this, but I have a very limited knowledge base to draw from, do you have any references for information on this matter?  I am very interested and with enough information, would be willing to participate in experimentation.
  • I know a guy who works on the protein level of the stack. I'll see if I can get him interested.

    Welcome to the forum @DarkDJ117!
  • bumping this due to usefulness with tetra chrome thread.
  • well, here are the notes @Rubix had on SWS1 http://pastebin.com/JDfcJqac
    It's a little bit of leg-work out of the way, maybe. I'd really like to try this too. I'll x-post this into the tetrachrome thread.
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