12:48 GMT16 January 2021
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    A Crisper Way of Gene Editing

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    The world of genome surgery has moved closer with the development of the so called ‘CRISPR’ genome editing technique. As many as 20 clinical trials are getting under way, mostly in China, however this technique has applications far beyond medicine.

    What is this new technique, and why is it hailed as a breakthrough, if it is, and is it safe? Jon Cohen, a respected science writer who writes for the American magazine Science shares his knowledge.

    Jon describes CRISPR as being a way to cut DNA, "it was adapted from bacteria which do this naturally, and they do this as part of their immune defense system. Scientists figured out a way to do that inside mammalian cells including humans. By cutting the DNA, two things can happen: you can cut out something that is bad in a gene… CRISPR can target it very specifically, then the body will naturally repair the DNA. The second thing you can do is cut the DNA and splice in something else. It is a pair of molecular scissors that cuts DNA."

    At the present time, there are two ways that CRISPR can be used. Firstly to treat cells that have been taken out of the body and the second, to inject CRISPR directly into the body. "For example, diabetes, is a specific cell that lives in the pancreas, so in theory you could inject the CRISPR molecule into your pancreas, and it would seek out those broken cells and try to fix them. But this is a highly theoretical idea and nobody is proposing to do that. That's the general idea, and for many diseases in humans you don't need to fix every single cell to fix the disease. But this still remains in the realm of possible; it is not even in the realm of probable as yet. A lot of people are excited about CRISPR because it is so much easier and cheaper to do than previous techniques that did this same thing, such as the technique that modifies DNA in people who are living with HIV…."

    The technique itself can be said, in theory, to be fairly simple: "In the body there are enzymes which are capable of cutting DNA. CRISPR takes enzymes to a very specific part of DNA with great precision and lets those enzymes cut the DNA….We have 3.2 billion nucleotides that make up the DNA in our body. You can tell CRISPR to go one nucleotide and cut right there. That's spectacular. The question is, do you hit the target, because if you don't that is called an off-target effect and the side effects of that could be dramatically bad. That's what we don't know right now — how common are the off-target effects."

    The off-target effect can be closely monitored when pulling cells out of the body and modifying them, before they are put back into the body. The big question is what can one do about the off-target effect is when CRISPR is injected directly into the body. "The answer is possibly nothing," Jon says. "But I don't want to create Frankenstein scenario. CRISPR is being identified by thousands of people around the world, and they are addressing these issues, and are getting better and better at creating CRISPR constructs that don't have off-target effects. So in time I think it is entirely feasible that there will be safe ways to do this….You have to bear in mind that we have been doing gene therapy for quite a while, where we put a harmless virus into the body that shuttles in some gene that you want, we do that already,…the potential upside of this is huge. And it is more than just medicine, this is a huge industry now for agriculture for example."

    A debate ensues concerning whether with CRISPR you are introducing anything foreign, and thus changing the organism. Host John Harrison argues that even if you are not introducing something new you are still changing it. Jon however argues that when a farmer takes one strain of corn and crosses it with another he is creating something that wasn't there before. "Corn wasn't a food that people ate, it was a grass that grew, and farmers did these experiments to create the food that we eat….The question is, where do you draw that line."

    The question of regulatory authorities is discussed; as the only global health authority which could supervise how CRISPR is used — The WHO — has no teeth to enable it to enforce resolutions. Jon points out that every country has been faced with regulating medical advances on their own; the EU does it in Europe and so on. "I think there has been a lot of attention paid to regulatory functions in most countries in the world. There are no countries in the world that I know of which allow you to do hugely unethical studies on humans. Some countries are stricter than others."

    Development of CRISPR is moving very fast. In the space of a few years we have gone from a few papers to thousands a year on this subject, Jon says. But "anyone who tells you the timeline is a charlatan. Will it happen sooner than most people think?, I think so, because there is so much effort and so much money going into this, that I think something will surface and surprise people in how quickly it proves its worth. But if you look at the companies that are pursuing this, they are trying to choose low hanging fruit to begin with. Agricultural companies are probably going to be first, because it is much easier to do the testing in plants than in humans."

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    human genome, Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR), Science, medicine, DNA, China
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