Updated on
What did the project achieve?
“We’re now one step closer towards developing a new, highly targeted gene therapy for X-linked lymphoproliferative disease (XLP),” says Professor Claire Booth of UCL Great Ormond Street Institute of Child Health. “This cutting-edge approach has the potential to offer a new cure – giving boys born with this life-limiting condition the hope of living healthy, normal lives.”
XLP is a rare genetic condition that affects boys, making them extremely vulnerable to life-threatening infections and at increased risk of developing lymphoma, a type of cancer. Currently, the only potential cure is a bone marrow transplant, but finding a suitable donor can be challenging. Unfortunately, if treatments come too late or donors can’t be found, boys with XLP remain at risk of losing their lives.
In previous research, Professor Booth and her team developed a new gene therapy that involved inserting a working copy of the faulty gene into the patient’s own T-cells – a type of white blood cell – and returning these to the body. Following encouraging results in the laboratory, the team is now preparing to launch a clinical trial of this promising new treatment, which is expected to open in early 2026.
Building on this work, the team is taking this step further by using the latest gene editing technologies to precisely correct the faulty gene in a child’s blood stem cells. Unlike earlier methods, this technique repairs the gene at its exact location in the genome, which could make it safer and more effective.
“Our long-term goal is to collect a patient’s blood stem cells, correct them in the laboratory using gene editing, and then return the edited cells to the patient, where they can rebuild a fully functioning immune system,” explains Professor Booth. “Because these cells can develop into all types of blood cells and should persist for life, this could offer a lasting cure.”
In their most recent work, the team tested different ways to introduce their gene editing tools into patient blood stem cells.
“We’re now testing the most promising approach in a laboratory model to find out whether the corrected patient blood stem cells can survive in the bone marrow and regenerate a fully functional immune system,” says Professor Booth. “If successful, we aim to move this treatment into clinical trials within the next three to four years.”
This research was completed on
X-linked lymphoproliferative disease (XLP) is a rare, severe genetic illness that affects the immune system. Affected boys typically become sick during childhood or early adolescence – and sadly, without a bone marrow transplant, they will usually lose their lives. Professor Claire Booth at the UCL Great Ormond Street Institute of Child Health is aiming to develop a new treatment using cutting-edge gene editing technologies to correct the faulty gene in a child’s blood stem cells. Building on previous work in this area, this exciting new approach has the potential to cure the disease by repopulating their immune system with healthy cells – saving lives and preventing illness in boys born with XLP.
How are children’s lives affected now?
Caused by faults in a single gene, boys born with XLP have an increased risk of developing life-threatening infections and some will develop a type of cancer caused lymphoma. Currently, the only available treatment is a bone marrow transplant – but the outcome will depend on finding a well-matched donor and carrying it out before any symptoms develop.
“Unfortunately, a successful transplant isn’t always possible – it may happen too late or a suitable donor can’t be found,” says Professor Booth.
Gene therapy, which involves inserting a correct copy of the gene into the patient’s own blood cells in the laboratory before transplanting them back into their body, offers hope of a new cure for XLP that doesn’t involve waiting for a donor.
“However, the conventional approach inserts the gene into a random location in the patient’s genome and, unlike in healthy people, it is permanently switched on – which could lead to unwanted effects,” says Professor Booth.
How could this research help?
“Our goal is to use newer targeted gene editing technologies to develop a safer way to cure boys with XLP,” says Professor Booth.
The team is building on previous work where they have shown they can use gene editing to correct the faulty gene in its natural location in white blood cells collected from patients, restoring normal gene activity and cell function.
“We will now use this approach to correct the faulty gene in patient blood stem cells,” says Professor Booth. “As these can develop into all types of blood cells, this could offer a curative treatment.”
After perfecting their gene editing techniques, the researchers will then transplant corrected patient blood stem cells into a laboratory model to find out whether they can generate a fully functional immune system.
“If our results are promising, this could pave the way to a clinical trial and lead to an exciting new treatment for boys with XLP – and accelerate progress towards similar cures for other serious genetic diseases,” says Professor Booth.
Research table
Project details
| Project Leader | Professor Claire Booth, MBBS MSc PhD |
| Location | Molecular and Cellular Immunology Section, UCL Great Ormond Street Institute of Child Health |
| Project Team |
Dr Ben C Houghton, BSc PhD
Professor Adrian J Thrasher, MBBS PhD |
| Grant Awarded | |
| Grant Amount | £173,918 |
| Start Date | |
| End Date | |
| Duration | 18 months |
| Grant Code (GN number) | GN2814 |
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