World’s first personalised DNA editing treatment

Approximate read time: 5 minutes

In August 2024, a boy called KJ was born in Philadelphia, United States, with a rare genetic disease that gave him only a 50% chance of surviving infancy.^[1] This disease, known as carbamoyl phosphate synthetase I (CPSI) deficiency, is caused by genetic mutations that prevent the breakdown of ammonia—a poisonous waste product produced by our bodies. If unchecked, an accumulation of ammonia can quickly lead to permanent brain damage, coma or death.^[2]

Ammonia started to build up in KJ’s blood in the two days after his birth. In less than seven months, a team of scientists at the University of Pennsylvania identified the specific mutation causing KJ’s condition and then designed, tested and received approval to administer a new, personalised treatment intended to fix the error in his DNA causing the condition. After receiving three rounds of treatment, KJ’s ammonia levels now appear to be under control.^[3] He was discharged on 3 June 2025, leaving hospital for the first time at 10 months old.^[4]

This is the world’s first ever personalised gene-editing therapy; that is, a treatment designed to fix a DNA mutation in a specific individual. Scientists hope that such personalised gene therapies will soon be used to fix the underlying causes of rare genetic disorders for which there are currently very few treatments.

1. How personalised gene editing works

KJ has a specific, ultra-rare mutation in his DNA. DNA consists of chains of molecules that can be thought of as long strings of letters (either A, T, G or C) containing the code for life. A gene is a section of DNA that codes for a particular function in the body. Humans have over 20,000 genes and each one is typically tens of thousands of letters long. One of them, known as CPS1, contains a code that is essential for breaking down ammonia. KJ was born with a single-letter error in this gene—where everyone else has a G, he has a T.

Humans all have many mutations in various parts of their DNA. Most are completely harmless. Unfortunately, KJ’s specific mutation disrupted the CPS1 gene code in such a way that ammonia could no longer be broken down.

To fix this error, scientists designed a treatment known as ‘base-editing’ which built on a technology known as CRISPR (pronounced ‘crisper’, which stands for clustered regularly interspaced short palindromic repeats), the creators of which were awarded the 2020 Nobel Prize in chemistry.^[5] Such CRISPR-based tools are essentially molecular machines. In this case, the machine first identified a specific sequence of 20 letters out of all 3.2bn letters in human DNA. Once in the correct location, KJ’s DNA was edited with surgical precision to change the single-letter error. The hope is that if this mutation can be fixed then KJ’s liver will break down ammonia like normal.

2. Future of gene-editing treatments

Although KJ’s case is the first use of personalised gene-editing treatment, it is not the first medical use of gene editing. In 2023, the UK became the first country to approve medicine based on CRISPR technology to edit human DNA, which has been available on the NHS in England since January 2025.^[6] Known as Casgevy, this treatment targets two blood diseases (sickle cell disease and β-thalassemia) by editing a haemoglobin gene. These diseases are among the most common genetic disorders in the UK, with sickle cell disease impacting one in every 2,000 live births in England.^[7]

KJ’s case is unique in that his treatment was designed for his specific mutation. Such personalisation can be achieved with CRISPR-based technologies by modifying only a few components of the ‘molecular machine’ to target a range of different mutations. Therefore, this technology could have widespread implications because, although each mutation may be rare, together, genetic diseases affect hundreds of millions of people globally.

The leader of this project, Professor Kiran Musunuru, believes the platform-based nature of this approach could also streamline the regulatory approval process.^[8] The US Food and Drug Administration has recently begun granting platform technology designations.^[9] The aim is to allow new technologies based on a common ‘platform’ to be approved more quickly rather than requiring separate independent approval for each variation of a related technology.^[10] Faster approval of new personalised CRISPR-based technologies could allow people to be treated earlier—potentially even before birth—and make treatments more financially viable.^[11]

The cost of KJ’s treatment is not known as many of the companies involved worked for free. However, such personalised gene therapies are likely to be very expensive, at least initially. For example, the previously mentioned Casgevy costs £1.65mn per course despite being a ‘one-size-fits-all’ treatment.^[12] Nevertheless, Musunuru believes the price of gene-editing treatments could fall dramatically due to economies of scale.^[13]

As KJ grows up, he will be closely monitored to confirm how well this novel treatment has worked. Scientists hope he could be the first of many to have their lives transformed by this technology.

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Cover image by Freepik.