NIH-supported gene-editing platform lays the groundwork for developing personalized gene therapy treatments. 

Adapted from the NIH website, May 2025.

A team supported by the National Institutes of Health (NIH) has developed and safely delivered a personalized gene editing therapy to treat an infant with a life-threatening, incurable genetic disease. The infant, who was diagnosed with the rare condition carbamoyl phosphate synthetase 1 (CPS1) deficiency shortly after birth, has responded positively to the treatment. The process, from diagnosis to treatment, took only six months and marks the first time the technology has been successfully deployed to treat a human patient. The technology used in this study was developed using a platform that could be tweaked to treat a wide range of genetic disorders and opens the possibility of creating personalized treatments in other parts of the body.

A team of researchers at the Children’s Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania (Penn) developed the customized therapy using the gene-editing platform CRISPR. They corrected a specific gene mutation in the baby’s liver cells that led to the disorder. CRISPR is an advanced gene editing technology that enables precise changes to DNA inside living cells. This is the first known case of a personalized CRISPR-based medicine administered to a single patient and was carefully designed to target non-reproductive cells so changes would only affect the patient.

CPS1 deficiency is characterized by an inability to fully break down byproducts from protein metabolism in the liver, causing ammonia to build up to toxic levels in the body. It can cause severe damage to the brain and liver. Treatment includes a low protein diet until the child is old enough for a liver transplant. However, in this waiting period there is a risk of rapid organ failure due to stressors such as infection, trauma, or dehydration. High levels of ammonia can cause coma, brain swelling, and may be fatal or cause permanent brain damage.

The child initially received a very low dose of the therapy at six months of age, then a higher dose later. The research team saw signs that the therapy was effective almost from the start. The six-month old began taking in more protein in the diet, and the care team could reduce the medicine needed to keep ammonia levels low in the body. Another telling sign of the child’s improvement to date came after the child caught a cold, and later, had to deal with a gastrointestinal illness. Normally, such infections for a child in this condition could be extremely dangerous, especially with the possibility of ammonia reaching dangerous levels in the brain.

“We knew the method used to deliver the gene-editing machinery to the baby’s liver cells allowed us to give the treatment repeatedly. That meant we could start with a low dose that we were sure was safe,” said CHOP pediatrician Rebecca Ahrens-Nicklas, M.D., Ph.D.

The scientists announced their work at the American Society of Gene & Cell Therapy Meeting on May 15th and described the study in The New England Journal of Medicine.

Starting the care journey isn't always simple 

Source: United Kingdom National Health Service National Genomics Education Program

Rare disease patients will often be seen by numerous healthcare professionals across several different specialties, all of whom may offer diverging opinions or diagnoses. This usually involves multiple appointments that are geographically dispersed, often with little communication between services – which can lead to an incorrect diagnosis or even delivery of the wrong treatment. This experience is so common within the rare disease community that it has its own name: the diagnostic odyssey

A person living with an undiagnosed condition will often have no relief from symptoms during their journey to diagnosis. They may also face doubts and dismissal from healthcare professionals. Emotions and challenges experienced can include:

• feelings of isolation, fear and stress;

• deterioration of physical and mental health;

• financial difficulties;

• impacted career and education opportunities; and

• breakdown of personal and/or familial relationships.

In working out how best to support someone with a rare condition, there is often a process of trial and error. As rare diseases present with so many unknowns, it is important that healthcare professionals  work together to deliver the best possible outcome for the patient.

It's important to remember that, from the patient’s perspective, receiving a diagnosis is not the only thing that matters: the way the diagnosis is obtained and delivered, and the ways which the patient is supported through the process, are both crucial to improving the rare disease patient experience and health outcomes.