Carbamoyl phosphate synthetase I

Years later, he helped lead another historic application of genetic editing.

Baby KJ was born with a CPS1 deficiency, which is a rare and potentially fatal urea cycle disorder.

His team developed a personalized CRISPR-based editing therapy designed specifically around KJ's genetic variant.

We're exploring personalized CRISPR therapies from common diseases like cardiovascular disease to PKU, all the way to ultra-rare disorders in this conversation.

Was it an injection for him?

Yeah, same sort of thing, an infusion, intravenous infusion.

Trillions of, uh, you know, these soap bubbles with the cargo, but the GPS pointed at his particular variant in his gene, in a gene called CPS1, causing CPS1 deficiency, which is a devastating urea cycle disorder.

And so it was really about, okay, start with the most common disease or one of the most common diseases, try to protect the world from heart disease and, you know, you can imagine once these therapies become available, you could deploy widely, and if enough people in the population took it, it would push off heart attacks and strokes by decades.

So they were looking at genetic diseases.

They had a database of patients with what's called a CPS1 deficiency.

CPS is called carbamoyl phosphate synthetase.

which doesn't mean much to most of your listeners, but we'll move on.

But in the males, it was probably compensated for by the masculization of the kidneys.

But in any case...

In the women, they showed that it was, yes, indeed, it was the glycine surplus caused by the deficiency of this enzyme function, CPS1, which was responsible for their lower incidence of MACE.

It was like a 12.5% decrease, and it was very, very significant.

I wanted to start with the story of baby KJ.

He was born in 2024 with a deadly genetic disorder called CPS1 deficiency, and he is now healed thanks to the use of a gene editing method called base editing.

David, could you talk about that case? What is base editing and how is it used?

Baby KJ's story is a remarkable one, not just for the science and the medicine, but also for the impact it has had in awakening the general public and our government leaders to the fact that we are not always beholden to the misspellings in our DNA.

And within just a day or two of being born, the blood test revealed that baby KJ's ammonia levels in his blood were off the charts, which is dangerous and a sign that there's a problem with the baby's ability to process protein, resulting in levels of ammonia that are too high.

Ultimately, this can cause brain damage and death.

Baby KJ was then sequenced, and the DNA sequence revealed that he had inherited two mutated copies of the gene called CPS1.

And so a team decided