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Engineering the composition and fate of wild populations with Medea and ClvR: uses and development of ClvR

Part 2 of 2
Published on May 31, 2023   26 min

A selection of talks on Plant & Animal Sciences

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0:00
This is part two of the talk on Medea and ClvR elements. What I want to do is to very briefly again, summarize the key characteristics of the ClvR elements that I ended Part 1 with. Then we're going to go on in the rest of this talk to talk about ways we can use this biology and molecular biology to do interesting things.
0:28
Just to summarize, a ClvR element is really simple. It's just a Cas9 and guide RNAs that bring about cleavage, and inactivation of an endogenous version of an essential gene. Along with that, we have the re-coded version of that same essential gene that's resistant to cleavage and that can support survival of individuals who lack any endogenous copies of that essential gene. What we like about this kind of element is that you can use any sequence specific DNA cleavage tool that you have, whether it's a nuclease, a base editor or something else, any essential gene can serve as a target. The rescue is just a re-coded version of the essential gene, and the regulatory sequences simply need to include a component that at least is expressed in the germ line, even if it's also expressed elsewhere.
1:29
We start to see how this can become more interesting. The point I want to emphasize here is that when you get past generations six or seven, here in this ClvR^dbe, what you notice is that for all of these ClvRs, you end up in a situation where every wild-type endogenous copy of the essential gene has been cleaved. When you've done that, you've actually done something really interesting, which is you've made the entire population now completely dependent on the re-coded rescue carried by the ClvR element itself. What you've done is you've literally addicted the population to a new version of this essential gene. Let's look at how we can potentially take advantage of that.
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Engineering the composition and fate of wild populations with Medea and ClvR: uses and development of ClvR

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