In a landmark moment for medical science, an infant, K.J. Muldoon, became the first human to receive a personalised Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based gene-editing therapy, aimed at treating a rare and life-threatening genetic condition. This unprecedented intervention was carried out by a collaborative team at the Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania’s Perelman School of Medicine.
Carbamoyl Phosphate Synthetase 1: Deficiency and its Dangers
The infant was born, in August 2024, in Philadelphia. Soon after birth, he was diagnosed with a rare metabolic condition known as severe Carbamoyl Phosphate Synthetase 1 (CPS1) deficiency. This (autosomal recessive) disorder, caused by mutations in the CPS1 gene, severely impairs the body’s ability to break down ammonia, a toxic byproduct of protein metabolism. When ammonia accumulates in the body, it could lead to devastating consequences including brain swelling, coma, and permanent brain damage, or even death.
CPS1 deficiency typically manifests within days after birth. In this infant’s case, ammonia began to build up in his bloodstream within 48 hours. The standard treatment for this condition involves a restrictive low-protein diet and medications that help to reduce ammonia levels. The only long-term solution is a liver transplant.
However, infants must reach a certain level of medical stability and maturity to undergo such a complex surgical procedure, leaving them vulnerable during this critical early period. For many, this waiting period could be fatal or lead to permanent neurological damage.
The Innovation: Personalised Gene-Editing Using CRISPR
Given the high stakes and the limitations of the existing treatments, the infant’s family was presented with an experimental option never before used in a human patient. It was a personalised gene-editing therapy based on CRISPR technology. CRISPR allows scientists to make precise alterations to specific locations in the human genome.
Gene-editing technologies had previously been used for disorders like sickle cell disease and beta thalassemia. This case marked that CRISPR was personalised for the first time to treat an individual patient’s unique genetic mutation. This required identifying the specific variant in the experimental infant’s DNA that disrupted the CPS1 gene and designing a custom base-editing solution to correct it.
The mutation involved a single-letter change in the infant’s DNA, where the normal gene had a ‘G’, his had a ‘T’. This minor alteration had a major effect, rendering his liver incapable of processing ammonia. Scientists designed a molecular machine that could locate the faulty gene segment, just 20 letters out of the 3.2 billion in the human genome and correct the error with surgical precision. This approach is known as base-editing and represents a sophisticated evolution of CRISPR technology.
Unlike standard CRISPR, which cuts both DNA strands, base editing allows direct conversion of one DNA letter to another without breaking the double helix, reducing the risk of unintended mutations. This precision also holds potential for treating other single- nucleotide polymorphism (SNP)-based diseases, which account for a significant proportion of genetic disorders.
Rapid Development of a Custom Therapy
The initiative to develop a personalised therapy for the experimental infant was led by Dr Rebecca Ahrens-Nicklas at CHOP and Dr Kiran Musunuru at the University of Pennsylvania. Both are a part of the National Institutes of Health (NIH)-funded Somatic Cell Genome Editing Consortium, which promotes collaboration between scientists working on genome-editing technologies.
After the infant’s diagnosis, the team moved swiftly. Within just six months, they had not only identified the mutation but further designed, tested, and manufactured a therapy specifically for him. The therapy was delivered using lipid nanoparticles that carried the CRISPR base editors directly to his liver cells.
Lipid nanoparticle delivery systems have also been used in mRNA COVID-19 vaccines including those from Moderna and Pfizer-BionNTech, demonstrating their safety and efficiency in delivering genetic material to cells where it can be translated into proteins that trigger an immune response.
He received the first infusion between six and seven months of age in February 2025. This was followed by two additional doses in March and April 2025. Remarkably, he experienced no serious side effects. In June 2025, he was healthy enough to be discharged from the hospital for the first time.
Impact of the Treatment
The impact of the treatment became evident soon after the administration. The infant began tolerating more protein in his diet, a key indicator that his liver was starting to process ammonia more effectively. He also required less medication to control ammonia levels. A particularly significant milestone was his recovery from common childhood illness, such as cold and gastrointestinal infections, without experiencing a dangerous ammonia build-up, something which could have been fatal before treatment.
While the results of the treatment are still preliminary and the infant will need lifelong monitoring, his early progress offers cautious optimism. The medical team emphasised that the potential to replicate this method for other patients with rare diseases is substantial.
A Model for Future Treatments
This historic achievement demonstrates the potential of personalised medicine in treating rare genetic conditions. The gene-editing tools used in the experimental infant’s case were developed on a platform that could be adapted for many other disorders. Although each rare disease might affect only a small number of people, collectively they impact many around the world.
The project leaders believe that platform-based development could streamline regulatory processes. Agencies such as the US Food and Drug Administration (FDA) have already begun recognising platform technologies, which may allow future variations of similar therapies to be approved more quickly. This has the potential to speed up treatment timelines significantly and make these therapies more accessible.
In India, similar platform-based models are being explored for gene therapies targeting sickle-cell anaemia under the National Sickle Cell Anaemia Elimination Mission (2023–47).
Scientific Collaboration and Support
The success of this treatment was made possible by wide-ranging collaboration between academic institutions, government agencies, and private sector contributions. Funding came from the NIH through various grants, especially from the Somatic Cell Genome Editing Program. Additional support came from CHOP’s Gene Therapy for Inherited Metabolic Disorders Frontier Program. Companies such as Acuitas Therapeutics, Integrated DNA Technologies, Aldevron, and Danaher Corporation also contributed by providing essential materials and technical support at no cost.
The researchers presented their findings at the American Society of Gene and Cell Therapy Meeting in May 2025, and the results were published in the New England Journal of Medicine.
Impact on the Infant Patient’s Family
For the parents, the journey has been deeply emotional—from the trauma of their infant’s early diagnosis and prolonged hospitalisation to the hope offered by this groundbreaking therapy. It reflects the broader human dimension of medical innovation. Their trust with the medical team enabled the experimental treatment undertaken not only to save their child but also to help other families facing similar challenges. Their decision to support this pioneering treatment has already begun to transform not only their infant’s life but the future of medicine for rare diseases.
Challenges and Potential
Despite the breakthrough, significant challenges remain. The cost of personalised gene therapies is likely to be extremely high, at least initially. For instance, Casgevy, a gene therapy approved in the UK for blood disorders, is priced at approximately £1.65 million per treatment. While the experimental therapy involved many in-kind contributions that lowered the costs, scalable production would require economic solutions.
There are also regulatory considerations. Personalised therapies involve manipulating an individual’s genome, raising concerns about long-term monitoring. However, targeting non-reproductive (somatic) cells in these treatments ensures that changes are confined to the treated individual and are not passed on to future generations.
Monitoring the infant over time will be essential to assess the long-term effects and durability of the gene correction. Nevertheless, the ability to design and deliver such therapies within months of diagnosis shows a transformative shift in present-day approach to medicine.
This experimental case marks a turning point in the application of gene-editing technologies to rare diseases. It demonstrates that, with the right combination of scientific innovation, institutional support, and family cooperation, it is possible to develop and administer life-saving, personalised treatments within an extraordinarily short timeframe. As science continues to advance, this case will likely be remembered as the beginning of a new era in gene-editing.
© Spectrum Books Pvt. Ltd.
