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Printable Handouts
Navigable Slide Index
- Introduction
- Key characteristics of ClvR elements
- The population becomes addicted to Rescue
- Population modification/adddiction followed by stimulus-dependent suppression
- The use of inteins with ClvR
- TS-ClvR population spread at different temperatures
- Think about…
- Resilience
- Engineered objects break
- Cycles of success and failure
- Resilience through renewal
- Control of transgene fate post-release
- A 2-locus ClvR for a measured, self-limited drive
- 2-locus50cM ClvR: mechanism of action
- 2-locus50cM ClvR: 5% fitness cost/allele (1)
- 2-locus50cM ClvR: 5% fitness cost/allele (2)
- Cleave and Rescue: ClvR
- Acknowledgements
- Thank you for listening
Topics Covered
- Gene drive
- The use of inteins with ClvR
- Cycles of success and failure
- Control of transgene fate post-release
- 2-locus CLvR mechanism of action
Links
Series:
Categories:
Talk Citation
Hay, B.A. (2023, May 31). Engineering the composition and fate of wild populations with Medea and ClvR: uses and development of ClvR [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 7, 2024, from https://doi.org/10.69645/MVDY9378.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Bruce A. Hay has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Engineering the composition and fate of wild populations with Medea and ClvR: uses and development of ClvR
Published on May 31, 2023
26 min
Other Talks in the Series: Gene-Drives and Active Genetics
Transcript
Please wait while the transcript is being prepared...
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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