Gene Editing in X-Linked Agammaglobulinaemia
Research type
Research Study
Full title
Gene Editing in X-Linked Agammaglobulinaemia
IRAS ID
268882
Contact name
Adrian Thrasher
Contact email
Sponsor organisation
Institute of Child Health
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
X-Linked Agammaglobulineamia (XLA) is an inherited immunodeficiency affecting 1 in 250,000 births. It is caused by a mutation in Bruton’s Tyrosine Kinase (Btk) which is encoded in the X chromosome. This leads to antibody deficiency and patients suffer severe, recurrent infection. Conventional therapy comprises life-long infusions of immunoglobulin but even with this therapy patients may still have frequent. Currently a safe and definitive treatment is lacking.
Recent progress in gene therapy has provided proof of principle in a number of Immunedeficiencies including SCID, Wiskott Aldrich Syndrome and CGD. However, the gene is integrated into host DNA at a semi-random location. While effective, for conditions where accurate gene expression and regulation is desirable, it may not be fully effective, and there may be additional problems associated with dysregulated gene expression. An alternative novel approach is to use accurate gene editing technology in order to insert a therapeutic transgene in a location that enables physiological gene expression. This project will be a pre-clinical feasibility study to establish this technique for the treatment of XLA.
At first, specialised enzymes will be transferred into cells to cut the DNA at an area in the BTK gene. Subsequently a correct version of the gene will be delivered into cells using a viral vector and this will be transferred into the area of the cut. We aim to then test these cells in immune deficient mice and observe whether the mice start to make B Cells and Immunoglobulins.
In recent years the cost of whole genome sequencing has fallen greatly and now it is easier to elicit the genetic cause of diseases including Primary Immunodeficiencies. Gene editing has the potential to reverse these mutations. If this project is successful then it can be adapted for other immunological and haematological conditions.
REC name
North East - York Research Ethics Committee
REC reference
19/NE/0364
Date of REC Opinion
24 Jan 2020
REC opinion
Further Information Favourable Opinion