Extra: Could base editing lead to designer babies?
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Future Proof Extra with Jonathan McRae. Proudly supported by Research Ireland on Newstalk.
Welcome back to Future Proof on Newstalk. I'm Jonathan McRae. If you'd like to get in touch with the show, you can email us at science at newstalk.com. Now, you might remember the infamous case of Chinese scientist He Jiankui, who in 2018 used CRISPR-Cas9 to edit the DNA of human embryos that were then implanted. He ultimately spent three years in prison for illegal medical practice and his work was widely condemned across the globe. His approach was ill-advised for a number of different reasons, but a new process called base editing has eliminated a lot of the risk associated with embryo editing. So is this new and is it something we want? Oliver Bower is founding scientist at Preventive. He joins me now.
So people who are familiar with the programme may have heard of CRISPR-Cas9, but if they're new to the programme or haven't heard of it, if you wouldn't mind just explaining what it is, please.
Sure thing. So CRISPR-Cas9 is effectively a pair of molecular scissors. So it uses two components, the CRISPR component and the Cas9 component. So CRISPRs are basically a form of genetic sequences that are used to program the enzyme Cas9. So the evolutionary history of this is that bacteria and viruses are constantly at battle with one another. and to do this viruses inject their DNA into bacteria and then they seek to hijack their machinery and make more copies of themselves. So the bacteria's defense mechanism is to try to take some of these viral sequences and then insert them into their own genome. That way when they're attacked again they can start producing all these sequences And then these sequences are a template used to latch onto other viral sequences.
And then that works in complement with the Cas9 enzyme. So Cas9 enzyme, it is an enzyme, a biological catalyst, speeds up chemical reactions. So when given a given guide sequence, it will bind to that DNA and cut it apart. That's the general process that works. So it works kind of like a cut and paste mechanism, like a pair of molecular scissors.
Yeah, you've described that really well. But in terms of how we could use something like that to specify a particular part of a human genome, how do we program the bit that we want when it's a human genetic sequence that we're looking at?
So overall, the genetic sequence, you've got your four letters, your A, G, C, and T. And then the guide RNA itself, so this short section of material that you provide it, is usually about 20 base pairs in length. So in this way, this can be programmed almost without fail to any sequence that you can give it, whether that would be a human gene or a cow gene or a bacterial gene.
And this is so exciting. Jennifer Doudna, one of the researchers who was acknowledged with the Nobel Prize for this work, basically released this technology that allowed us to do amazing things, but it wasn't perfect.
What is base editing and how does it differ from CRISPR-Cas9 cutting?
What is the difficulty with CRISPR-Cas9 and why can we not use it immediately now to fix so many genetic diseases and fix potential diseases in embryos today?
Yeah, so the real challenge with it is that while it is this highly programmable system, I mean, this is the pure beauty of it, you can give it really any 20 base pair sequence and it will find and identify that locus. The problem is, as I described, this is a bacterial defense mechanism used to target and destroy viral DNA. In this way, it is very good at cutting DNA, but the cell's response to this, especially a human cell, its response to this, and for its purpose of doing precision genome editing, this is not how it's designed. It's designed to be a perfect cutter, but what follows after that cutting and to seamlessly bring these strands together or introduce edits, this is much more down to error-prone cell machinery.
So in this way, the editing system alone is very good for targeting DNA, but for making precision edits, this is the main challenge.
The cutting of the DNA I get, but is the replacement DNA, does that come from just the environment?
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