GENTLE V 1.0
Research type
Research Study
Full title
Base editing for gentle repair of blood and immune disorders with fragile DNA
IRAS ID
325015
Contact name
Waseem Qasim
Contact email
Sponsor organisation
UCL Great Ormond Street Institute of Child Health, Research and Development
Duration of Study in the UK
3 years, 3 months, 28 days
Research summary
Certain changes in a child's DNA can lead to complex medical conditions that affect their blood, immune system, and overall growth and development. These conditions are called DNA repair disorders. At GOSH, we have expertise in treating some of these conditions by performing stem cell transplants. These transplants are challenging because the chemotherapy, used to make room for donor stem cells, can cause additional damage. Researchers have been exploring gene therapy to fix patients’ bone marrow, often using a virus to add genes into the DNA. However, this approach can still trigger harmful responses. Therefore, more “gentle” strategies are necessary.
In our project, we propose developing alternative treatments using a new technology called genome 'base-editing.' This involves modifying DNA without causing additional damage. We will design, develop, and test new tools to correct the DNA code back to its normal state. This might help to find new long-term treatments for these disorders.
The study will enrol patients from birth age up to 65 years with suspected or defined genetic mutations of the immune or DNA repair systems, as well as their parents and siblings suspected or known to carry mutations.
Initially, we will work with cells that have already been collected and stored from our patients. The most effective approaches will then be used to correct blood and stem cells. Extensive testing will be done to ensure that the DNA has been successfully restored to normal and to check for any unintended effects.
Patients will be approached and recruited at GOSH during routine visits. We will use previously stored samples as far as possible, otherwise we will collect blood, bone marrow and skin samples during planned appointments.
The study is funded by Great Ormond Street Hospital Charity and it is expected to last 3 years.REC name
West Midlands - Solihull Research Ethics Committee
REC reference
23/WM/0249
Date of REC Opinion
9 Jan 2024
REC opinion
Further Information Favourable Opinion