Ormond Street Hospital, Brunell, Cambridge discussed on The Naked Scientists


I this week scientists in Cambridge, have developed a system to fix a class of devastating genetic diseases called mighty Konjil enzyme defects. Charlie God a little boy who became a high profile case at great Ormond street hospital and who sadly died last year had one of these conditions. They Akot in structures called my to conjure which the plas als with energy don't function properly. This happens because some of them I to conjure which contain their own small piece of DNA carry genetic changes or mutations that prevent them from working properly Brunell. There might be a way to fix the problem. Pyan Gummidge from the medical research council's laboratory of molecular biology has developed a gene editing system that knocks out selectively, the defective, mighty Qendra. So they're replaced by healthy working ones, severe much diseases likely to result in the patient, not of leaving the hospital series, mobility, problems that likely have combs difficulties requiring round the clock. Most of the time and life can really be very, very difficult. And in slightly less severe cases being we'll chat bounds and struggling to live and independent life. We aimed to develop a system that would enable us to target the mutated, much contra DNA and take that percentage down from, say, ninety percent mutated down to fifty percent mutated, and hopefully someone who did have clinical disease, no longer has any more see you're talking about editing someone's Danes. We're talking about selectively, removing one entire population. Yeah. So how do that we took some genome engineering tools which have been developed in a in a different form for different purposes. Zinc fingers, zinc finger nucleus is to be precise and what these things do to target specific portions of DNA and cut it. If you cut the much Regino it gets degraded. And so if you can selectively cut the versions of much Gino that have a mutation, then usually remove them from. The total pool. And so hopefully you change the percentage of mutated verses healthy. We created these zinc fingers that would be specific to the mutation in this particular mouse that has a relatively mild form of my control disease, and it has a mutation which is very similar to human mutation. We tested it in mouse cells. If we could alter this ratio of mutates mutated, and then we put it into the mouse. So injecting into the bloodstream. The genetic instructions for for these Inc fingers using a harmless virus that's been repurpose for this kind of thing. This virus really, really likes to be taken up by heart cells. Predominantly, we measured the levels of healthy much DNA verses mutant sonogram about seventy percent and going down to about thirty thirty five. So that's well below the level of which people which symptoms. Yes, yes. Well, below the threshold cells generally liked to maintain a total number of my DNA molecules. They say it's a thousand if we. Moved, say, twenty percents of them will thirty percents of them will happen as the remainder will will be replicated. And so you'll basically every time you remove one molecule, your increasing the chance that it will be replaced by healthy one, how fine you I from doing this in humans. The beauty of approach is that it's generalize -able as every time we want to target and you mutation will we have to do is re engineer the parts that bind DNA and then will work that will take us a certain period of time a few months perhaps to design some new ones to human -tations and then to get ourselves into a position to be performing clinical trials in humans could take a little bit longer. We're hoping to have something on the concert in the next year or so. The mutation 's in people from Mike konczal disease different from each other. And if so, do you have to personalize this tool for every single person that you treat? There is a pretty broad selection. Yeah, of of much conjul mutations that the current humans and cause disease, but there are some real. Standout candidates that the pay much more commonly than others. For example, there's one which accounts are about thirty percent of all Michael DNA mutations in humans. So there is definitely going to be required level of reengineering different people in personalized medicine kind of approach. But a good portion of the population should be served by handful of these therapies. You're just doing netted might conjure DNA all them any risk to the neatly DNA..

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