Baby Is Healed With World’s First Personalized Gene-Editing Treatment

bnew

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A close-up portrait of newborn KJ, who has a tube coming out of his nose and a tiny felt football next to him. He is swaddled tight and appears to smile slightly with his eyes closed.

KJ Muldoon was born with a rare genetic disorder, CPS1 deficiency, that affects just one in 1.3 million babies.Credit...Muldoon Family

Baby Is Healed With World’s First Personalized Gene-Editing Treatment​


The technique used on a 9½-month-old boy with a rare condition has the potential to help people with thousands of other uncommon genetic diseases.

KJ Muldoon was born with a rare genetic disorder, CPS1 deficiency, that affects just one in 1.3 million babies.Credit...Muldoon Family

By Gina Kolata

  • May 15, 2025

Leer en español

Something was very wrong with Kyle and Nicole Muldoon’s baby.

The doctors speculated. Maybe it was meningitis? Maybe sepsis?

They got an answer when KJ was only a week old. He had a rare genetic disorder, CPS1 deficiency, that affects just one in 1.3 million babies. If he survived, he would have severe mental and developmental delays and would eventually need a liver transplant. But half of all babies with the disorder die in the first week of life.

Doctors at Children’s Hospital of Philadelphia offered the Muldoons comfort care for their baby, a chance to forgo aggressive treatments in the face of a grim prognosis.

“We loved him, and we didn’t want him to be suffering,” Ms. Muldoon said. But she and her husband decided to give KJ a chance.

Instead, KJ has made medical history. The baby, now 9 ½ months old, became the first patient of any age to have a custom gene-editing treatment, according to his doctors. He received an infusion made just for him and designed to fix his precise mutation.

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Doctors Heal Infant Using First Customized-Gene Editing Treatment​


Doctors applied a personalized treatment to cure a baby’s genetic disorder, opening the door to similar therapies for others.​


Developmental moments that he’s reaching show us that things are working. The prognosis for him was very different before we started talking about gene editing and the infusions.

Doctors Heal Infant Using First Customized-Gene Editing Treatment

0:48

Doctors applied a personalized treatment to cure a baby’s genetic disorder, opening the door to similar therapies for others.CreditCredit...Children’s Hospital of Philadelphia via Associated Press

The investigators who led the effort to save KJ are presenting their work on Thursday at the annual meeting of the American Society of Gene & Cell Therapy, and are also publishing it in the New England Journal of Medicine.

The implications of the treatment go far beyond treating KJ, said Dr. Peter Marks, who was the Food and Drug Administration official overseeing gene-therapy regulation until he recently resigned over disagreements with Robert F. Kennedy Jr., the secretary of health and human services. More than 30 million people in the United States have one of more than 7,000 rare genetic diseases. Most are so rare that no company is willing to spend years developing a gene therapy that so few people would need.

But KJ’s treatment — which built on decades of federally funded research — offers a new path for companies to develop personalized treatments without going through years of expensive development and testing.

Illnesses like KJ’s are the result of a single mutation — an incorrect DNA letter among the three billion in the human genome. Correcting it requires pinpoint targeting in an approach called base editing.

To accomplish that feat, the treatment is wrapped in fatty lipid molecules to protect it from degradation in the blood on its way to the liver, where the edit will be made. Inside the lipids are instructions that command the cells to produce an enzyme that edits the gene. They also carry a molecular GPS — CRISPR — which was altered to crawl along a person’s DNA until it finds the exact DNA letter that needs to be changed.

Image

A close-up view of a plastic syringe in a plastic bag with a clear liquid in the syringe.


One of the syringes of KJ’s treatment.Credit...Kiran Musunuru

While KJ’s treatment was customized so CRISPR found just his mutation, the same sort of method could be adapted and used over and over again to fix mutations in other places on a person’s DNA. Only the CRISPR instructions leading the editor to the spot on the DNA with the mutation would need to be changed. Treatments would be cheaper, “by an order of magnitude at least,” Dr. Marks said.

The method, said Dr. Marks, who wrote an editorial accompanying the research paper, “is, to me, one of the most potentially transformational technologies out there.”

It eventually could also be used for more common genetic disorders like sickle cell disease, cystic fibrosis, Huntington’s disease and muscular dystrophy.

And, he said, it “could really transform health care.”



The story of KJ’s bespoke gene-editing treatment began on the evening of Aug. 8, when Dr. Kiran Musunuru, a gene-editing researcher at the University of Pennsylvania got an email from Dr. Rebecca Ahrens-Nicklas at the Children’s Hospital of Philadelphia. A baby had been born, and genetic testing showed he had CPS1 deficiency.

Could he save the baby?

Dr. Musunuru had begun investigating the use of gene editing for fairly common gene mutations.

Developing a gene editor to treat patients is a deliberate process that can take years. But KJ did not have years to wait — perhaps as few as six months before a mounting risk of severe brain damage or death.

“At this point, the clock starts in my mind,” Dr. Musunuru said. “This is real life. This is not hypothetical.”

KJ’s disease is caused by an inability to rid the body of ammonia, a byproduct of protein metabolism. Ammonia builds up in the blood and crosses into the brain. His doctors put him on a diet that severely restricted protein — just enough for him to grow. He also had a medicine, glycerol phenylbutyrate, that helped remove the ammonia in his blood. But he still was at high risk for brain injury or death. Any illness or infection could make his ammonia levels soar and cause irreversible damage to his brain.

KJ lived at the hospital under 24-hour care.

Building a gene-editing system for the Muldoons’ baby and testing it was not easy.

“There was a lot of shooting from the hip,” Dr. Musunuru said.

Image

Dr. Kiran Musunuru, who wears a gray fleece and a stethoscope around his neck, poses with Dr. Rebecca Ahrens-Nicklas, who wears a light sweater and also has a stethoscope.


Dr. Kiran Musunuru, a gene-editing researcher at the University of Pennsylvania, left, and Dr. Rebecca Ahrens-Nicklas at the Children’s Hospital of Philadelphia.Credit...Children's Hospital of Philadelphia

He began working with Fyodor Urnov at the University of California, Berkeley, who made sure there were no unexpected and deleterious gene edits elsewhere in the DNA. Dr. Urnov is a part of an academic collaboration with Danaher Corporation, a company capable of producing the gene editor for KJ at a standard that would allow it to be used in a patient.

Danaher in turn collaborated with two other companies it owned, two additional biotechnology firms and another research institute, said Sadik Kassim, its chief technology officer for genomic medicines.

“At every step of the process, we were always expecting someone to say, ‘No, sorry,’” Dr. Kassim said. “And that would be the end of the story.” But his fears were unfounded. Danaher and the other companies charged only for the raw materials to make the drug, he added.

The F.D.A. also smoothed regulatory approval of the treatment, Dr. Ahrens-Nicklas said.

Dozens of researchers put all else aside for months.

In Berkeley, Dr. Urnov said, “scientists burned a vat of midnight oil on this the size of San Francisco Bay.” He added that “such speed to producing a clinic-grade CRISPR for a genetic disease has no precedent in our field. Not even close.”

David Liu of Harvard, whose lab invented the gene-editing method used to fix KJ’s mutation, said the speed was “astounding.”

“These steps traditionally take the better part of a decade, if not longer,” he said.

Only when the gene-editing solution was in hand and the F.D.A. approved the researchers’ work did Dr. Ahrens-Nicklas approach KJ’s parents.

“One of the most terrifying moments was when I walked into the room and said, ‘I don’t know if it will work but I promise I will do everything I can to make sure it is safe,’” she said.

On the morning of Feb. 25, KJ received the first infusion, a very low dose because no one knew how the baby would respond. He was in his room, in the crib where he had lived his entire life. He was 6 months old and in the seventh percentile for his weight.

Dr. Musunuru monitored the two-hour infusion, feeling, he said, “both excited and terrified.”

KJ slept through it.

Within two weeks, KJ was able to eat as much protein as a healthy baby. But he still needed the medication to remove the ammonia from his blood — a sign that the gene editor had not yet corrected the DNA in every affected cell.

The doctors gave him a second dose 22 days later.

Image

KJ stands on a soft surface in a hospital exam room with Dr. Musunuru and Dr. Ahrens-Nicklas, who both wear light yellow smocks and blue gloves and orange masks.


KJ is now well enough for the team to start planning to discharge him from the hospital and live at home, and he is meeting developmental milestones.Credit...Children's Hospital of Philadelphia

They were able to halve the medication dose. He got a few viral illnesses in that time, which normally would have triggered terrifying surges in his ammonia levels. But, Dr. Ahrens-Nicklas said, “he sailed through them.”

A week and a half ago, the team gave KJ a third dose.

It is too soon to know if he can stop taking the medication completely, but the dosage is greatly reduced. And he is well enough for the team to start planning to discharge him home from the hospital. He is meeting developmental milestones and his weight is now in the 40th percentile for his age, but it is not yet known if he’ll be spared a liver transplant.



The result “is a triumph for the American peoples’ investment in biomedical research,” Dr. Urnov said.

The researchers emphasized the role government funding played in the development.

The work, they said, began decades ago with federal funding for basic research on bacterial immune systems. That led eventually, with more federal support, to the discovery of CRISPR. Federal investment in sequencing the human genome made it possible to identify KJ’s mutation. U.S. funding supported Dr. Liu’s lab and its editing discovery. A federal program to study gene editing supported Dr. Musunuru’s research. Going along in parallel was federally funded work that led to an understanding of KJ’s disease.

“I don’t think this could have happened in any country other than the U.S.,” Dr. Urnov said.

Those who worked on saving KJ were proud, Dr. Urnov said.

“We all said to each other, ‘This is the most significant thing we have ever done.’”

A correction was made on

May 15, 2025

:

An earlier version of this article misstated the name of a society. It is the American Society of Gene & Cell Therapy, not Cell & Gene Therapy.



When we learn of a mistake, we acknowledge it with a correction. If you spot an error, please let us know at nytnews@nytimes.com.Learn more

Gina Kolata reports on diseases and treatments, how treatments are discovered and tested, and how they affect people.
 

Wargames

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You know what this is. It’s like when people would get sick in start trek and the doctors would give them a shot and their bodies would heal. Essentially they would have their genes over right any specific issue.

There should be an effort to speed this up for as many genetic diseases as possible.
 

OneManGang

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In before ignorant people completely overlook the negative impacts CRISPR could have on society including and not limited to its lack of regulatory oversight, its high eugenics potential and other ethical concerns about human social/genetic engineering and wealth inequality, and its ease of causing potentially dangerous and new disease.

But happy for these cacs :mjpls:
 

bnew

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In before ignorant people completely overlook the negative impacts CRISPR could have on society including and not limited to its lack of regulatory oversight, its high eugenics potential and other ethical concerns about human social/genetic engineering and wealth inequality, and its ease of causing potentially dangerous and new disease.

But happy for these cacs :mjpls:

be happy for a breh too.:sas1:



I received the new gene-editing drug for sickle cell disease. It changed my life.​

As a patient enrolled in a clinical trial for Vertex’s new exa-cel treatment, I was among the first to experience CRISPR’s transformative effects.

By

December 4, 2023

Jimi Oleghere seated in his home

MATT ODOM

On a picturesque fall day a few years ago, I opened the mailbox and took out an envelope as thick as a Bible that would change my life. The package was from Vertex Pharmaceuticals, and it contained a consent form to participate in a clinical trial for a new gene-editing drug to treat sickle cell disease.

A week prior, my wife and I had talked on the phone with Haydar Frangoul, an oncologist and hematologist in Nashville, Tennessee, and the lead researcher of the trial. He gave us an overview of what the trial entailed and how the early participants were faring. Before we knew it, my wife and I were flying to the study site in Nashville to enroll me and begin treatment. At the time, she was pregnant with our first child.

I’d lived with sickle cell my whole life—experiencing chronic pain, organ damage, and hopelessness. To me, this opportunity meant finally taking control of my life and having the opportunity to be a present father.

The drug I received, called exa-cel, could soon become the first CRISPR-based treatment to win approval from the US Food and Drug Administration, following the UK’s approval in mid-November. I’m one of only a few dozen patients who have ever taken it. In late October, I testified in favor of approval to the FDA’s advisory group as it met to evaluate the evidence. The agency will make its decision about exa-cel no later than December 8.



Related Story​

The first CRISPR cure might kickstart the next big patent battle


Vertex Pharmaceuticals plans to sell a gene-editing treatment for sickle-cell disease. A patent on CRISPR could stand in the way.

I’m very aware of how privileged I am to have been an early recipient and to reap the benefits of this groundbreaking new treatment. People with sickle cell disease don’t produce healthy hemoglobin, a protein that red blood cells use to transport oxygen in the body. As a result, they develop misshapen red blood cells that can block blood vessels, causing intense bouts of pain and sometimes organ failure. They often die decades younger than those without the disease.

After I received exa-cel, I started to experience things I had only dreamt of: boundless energy and the ability to recover by merely sleeping. My physical symptoms—including a yellowish tint in my eyes caused by the rapid breakdown of malfunctioning red blood cells—virtually disappeared overnight. Most significantly, I gained the confidence that sickle cell disease won’t take me away from my family, and a sense of control over my own destiny.

Today, several other gene therapies to treat sickle cell disease are in the pipeline from biotech startups such as Bluebird Bio, Editas Medicine, and Beam Therapeutics as well as big pharma companies including Pfizer and Novartis—all to treat the worst-suffering among an estimated US patient population of about 100,000, most of whom are Black Americans.

But many people who need these treatments may never receive them. Even though I benefited greatly from gene editing, I worry that not enough others will have that opportunity. And though I’m grateful for my treatment, I see real barriers to making these life-changing medicines available to more people.




A grueling process

I feel very fortunate to have received exa-cel, but undergoing the treatment itself was an intense, monthslong journey. Doctors extracted stem cells from my own bone marrow and used CRISPR to edit them so that they would produce healthy hemoglobin. Then they injected those edited stem cells back into me.

It was an arduous process, from collecting the stem cells, to conditioning my body to receive the edited cells, to the eventual transplant. The collection process alone can take up to eight hours. For each collection, I sat next to an apheresis machine that vigorously separated my red blood cells from my stem cells, leaving me weakened. In my case, I needed blood transfusions after every collection—and I needed four collections to finally amass enough stem cells for the medical team to edit.

The conditioning regimen that prepared my body to receive the edited cells was a whole different challenge. I underwent weeks of chemotherapy to clear out old, faulty stem cells from my body and make room for the newly edited ones. That meant dealing with nausea, weakness, hair loss, debilitating mouth sores, and the risk of exacerbating the underlying condition.



Jimi Oleghere leans on the fence beside his home

MATT ODOM

My transplant day was in September 2020. In a matter of minutes, a doctor transferred the edited stem cells into me using three small syringes filled with clear fluid. Of course, the care team did a lot to try and make it a special day, but for me that moment was honestly deflating.

However, the days and months since have been enriching. I’ve escaped from the clutch of fear that comes from thinking every occasion could be my last. Noise and laughter from my 2-year-old twin daughters and 4-year-old son echo through my home, and I’ve gained immense confidence from achieving my goal of being a father.

It’s clear to me from my experience that this treatment is not made for everyone, though. To receive exa-cel, I spent a total of 17 weeks in the hospital. Not everyone will want to subject themselves to such a grueling process or be able to take time away from family obligations or work. And my treatment was free as part of the trial—if approved, exa-cel could cost millions of dollars per patient.

Another potential barrier is that some people become enmeshed with their chronic disease. In many ways, your disease becomes part of your identity and way of life. The community of people with sickle cell disease—we call ourselves warriors—is a source of strength and support for many. Even the promise of a better life from a novel technology may not be strong enough to break that bond.




From few, to many

Other challenges are society-wide. In advancing new treatments, the US medical industrial complex has too often left a trail of systemic racism and unethical medical practices in its wake. As a result, many Black Americans mistrust the medical system, which could further suppress turnout for new gene therapies.


Related Story​

Three people were gene-edited in an effort to cure their HIV. The result is unknown.



CRISPR is being used in an experimental effort to eliminate the virus that causes AIDS.

Global accessibility has also not been a priority for most of the companies developing these new treatments, which I feel is a mistake. Some have cited the lack of health-care infrastructure in sub-Saharan Africa, which houses about 80% of all sickle cell disease cases globally. But that just sounds to me like a convenient excuse.

The options for treating sickle cell disease are very limited. Denying access to such a powerful and transformative treatment based on someone’s ability to pay, or where they happen to live, strikes me as unethical. I believe patients and health-care providers everywhere deserve to know that the treatment will be available to those who need it.

Conducting gene therapy research and clinical trials in African populations could allow for a more comprehensive understanding of the genetic diversity of sickle cell disease. This knowledge may even contribute to the development of more effective and tailored therapies—not only for Africans, but also for people of African descent living in other regions.

Even as a direct beneficiary of gene therapy, I often struggle with not knowing the full consequences of my actions. I fundamentally, at a cellular level, changed who I am. Where do we draw the line at playing God? And how do we make the benefits of a God-like technology such as this more widely available?

Jimi Olaghere is a patient advocate and tech entrepreneur.
 

OneManGang

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be happy for a breh too.:sas1:
Cool for him :salute:

Doesn’t change the fact gene therapy is a very frightening frontier we’re entering. Completely blindly. Lead gasoline and asbestos were wonder discoveries at one time too. Humanity should carry on with cautious optimism and strict regulation but the dollar trumps everything
 

bnew

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Cool for him :salute:

Doesn’t change the fact gene therapy is a very frightening frontier we’re entering. Completely blindly. Lead gasoline and asbestos were wonder discoveries at one time too. Humanity should carry on with cautious optimism and strict regulation but the dollar trumps everything

so black scientists worldwide should endeavor to master this science so we can be protected from bad actors. :ld:
 

151_Pr00f

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In before ignorant people completely overlook the negative impacts CRISPR could have on society including and not limited to its lack of regulatory oversight, its high eugenics potential and other ethical concerns about human social/genetic engineering and wealth inequality, and its ease of causing potentially dangerous and new disease.

But happy for these cacs :mjpls:

Every scientific advancement has potential to be used for harm but not necessarily so. If we took the slippery slope argument to the extreme we could say that we should abandon all advances in the field of biochemistry. How then could we justify untold future generations of people who would die and suffer unnecessarily from genetic disorders?
 

OneManGang

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Every scientific advancement has potential to be used for harm but not necessarily so. If we took the slippery slope argument to the extreme we could say that we should abandon all advances in the field of biochemistry. How then could we justify untold future generations of people who would die and suffer unnecessarily from genetic disorders?
"The scientists were so preoccupied with whether or not they could, they didn't stop to think if they should.”

We not only lack dominion over nature, we're subordinate to it and now here we are - with the opportunity to rewrite life at our fingertips that, just like nuclear power, nobody knew what to expect with genetic engineering, but they pressed the button and hoped for the best, just like you are doing now.”


Ian_Malcolm_%28Jeff_Goldblum%29.jpg


Edit: Extra banger of a quote from another character, Dr. Alan Smith: “Some of the worst things imaginable were done with the best of intentions.”
 

151_Pr00f

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"The scientists were so preoccupied with whether or not they could, they didn't stop to think if they should.”

We not only lack dominion over nature, we're subordinate to it and now here we are - with the opportunity to rewrite life at our fingertips that, just like nuclear power, nobody knew what to expect with genetic engineering, but they pressed the button and hoped for the best, just like you are doing now.”


Ian_Malcolm_%28Jeff_Goldblum%29.jpg

Good quote. I personally think it's potential for good is worth the risk, given we proceed responsibly.
 

OneManGang

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Good quote. I personally think it's potential for good is worth the risk, given we proceed responsibly.
That’s the part that scares me. CRISPR is game changing, but history has definitely shown me we’re gonna fukk shyt up using it irresponsibly and indiscriminately :dead:

On another note, people should really look deeper into the messaging of their favorite Sci Fi works. It’s all there. Games like Cyberpunk and Fallout, movies like Terminator and The Matrix (leaving out a bunch of titles and IPs), are HORROR stories. We should be treating them with reverence studying the messages they portray about real life society. Especially Cyberpunk, it’s the most likely to actually happen the trajectory we’re on.
 
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Wiseborn

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damn ... progress ... a beautiful thing.
It is but I don’t like it.

The implications are not good, But I’m happy that the baby is healthy and happier that a breh is at the forefront of this technology

One thing is for certain it will be a long while til a Black baby will benefit from it.
 
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