Jason Mast
speaker
28 appearances
1 recordings
1 series
first heard Jun 2025
last heard Jun 2025
Jason Mast’s voice in public audio — every appearance, attributed to the second.
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So baby KJ was born last summer. He was the Muldoon's fourth child.
They're told that he's quite healthy and we're going to put him in the NICU for now, but, you know, he'll be back with you very soon. And then basically within 48 hours, a nurse pulls Kyle aside, the father, and pulls up KJ's arm and drops it down. And instead of flopping, as you would expect a baby's arm or anyone's arm, really, it's to do, it kind of shutters down.
And what they find is that his ammonia levels are in the thousands, when it should be, you know, like 10 or 20. And this is very dangerous.
So they rushed KJ across the street, basically, to the Children's Hospital of Philadelphia from UPenn Hospital. And they immediately put him on medicines to bring down that ammonia, put him on a strict diet. And they sequenced his genome. And they say, okay, what exactly is the issue here? And they find that he has a mutation in this one gene.
But what they realize is that this is actually a mutation that might be editable, that we might be able to make a gene editing treatment for.
For the last couple years, they had been basically preparing for a baby like KJ. Because there had been all these advancements in gene editing over the last decade. Many of your listeners probably have heard vaguely of CRISPR. There's one drug already approved for sickle cell. There's more in the works.
But the advancements had come to the point where you could make these really fine-tuned changes in DNA. And that... both creates some opportunities and some challenges. And the opportunity is there you can like treat as, you know, happened with KJ ultimately.
You can treat an individual patient's mutation, but you can only treat maybe that patient or this small handful of patients with this one very precise mutation. In cases like KJ, you're going to need to actually make that treatment really quickly.
And so they were like, can we do this in time ourselves? Can we go from an infant and make a treatment in time to help them?
Yes. And they had been running what they called sort of time trials where they like would pick a variant that's in the literature or that Becca would encounter. And they would see how fast can we do this? Not with any intention of we're going to put this in a patient, but we can see how fast can we do this?
And initially it takes over a year, and that was a couple years ago, but they get faster and faster until they can do it in what seems like a number of months. And what that starts is basically a six-month sprint to can we build this therapy in time? And he brings in researchers and companies.
in California, in Boston, in Vancouver, in Iowa, all sprinting, working overtime to see can we build this treatment before KJ either needs a liver transplant or has an ammonia attack that's going to really cause some long-term damage.
They managed to get it tested in mice and monkeys. They managed to, you know, do some testing on it to make sure that it doesn't accidentally edit the wrong portion of the genome. They get companies who basically are willing to, like, manufacture this at relatively low cost or for free. It's not clear exactly... But they were able to sort of cut a deal with these manufacturers.
And at six months, baby KJ is treated with the first dose. This is in February. It's not amazingly effective, the first one, because it's a very small dose. They want to be very careful. But then they go for a second dose a few weeks later. And then the third dose, not yet clear how the third dose has gone.
But after the second dose, they were able to really lower the medications he had been on to control ammonia. And they were able to loosen his diet so he could start eating protein for the first time, really, and like growing. And they no longer expect to give him a liver transplant. And they're hoping he has a, you know, not cured, but a much more mild form of his condition.
There's basically a delivery vehicle that's required to get your gene editing machinery into the liver. And they use what's called a lipid nanoparticle, which is basically a tiny little soap bubble that's Very, very, very, very, very small. That's sort of the delivery vehicle. And then inside of that, you put basically two components.
There's a gene editing protein that's sort of a two-part protein. It nicks DNA, and it has a part that changes a single letter from one to the other. And then there's what's called a guide RNA, which is basically GPS coordinates that
So you have a GPS coordinate within the genome for which letter to switch, you have a protein that switches the letter, and then you have this sort of FedEx envelope of a soap bubble that gets it into the liver.
I feel like in general, in science journalism, we avoid words like miracle and like cure quite often. But it is like, it is amazing. This is not a thing that could have been done for most of, until like basically very, very, very recently. This is a thing that like... Researchers have been trying to do this being sort of, like, broadly treat these kinds of conditions for a very long time.
You can look back at, like, publications and how people talked in the 80s or 90s when they kind of thought they were on the threshold of being able to, you know, replace genes and do things like this, and they weren't, and it didn't work. And now you hear you have a baby like KJ, and we don't yet know what his life will hold.
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