EBV-handling disorders

2025-2027

This programme is a collaboration between Oxford (Chakraverty and Davies), Newcastle (Hambleton and Schim van der Loeff), IGI (Urnov) and ICH (Booth and Santilli) with IDT as a commercial partner.   

Our first piece of work will focus on inherited EBV-handling disorders.

Epstein-Barr virus (EBV) infects more than 90% of the world's population.  Some people's immune systems have trouble controlling the infection, which can cause conditions like exaggerated primary infection, EBV-driven neoplasia or haemo-phagocytic lympho-histiocytosis (HLH), and can lead to deadly cancers in 10% of those affected.

The current best treatment is bone marrow transplantation, but this carries its own risks and not all patients will have a suitable donor available. 

Ex vivo gene editing may be a good option to solve this problem: blood can be taken from patients, then the T cells and/or Haematopoetic Stem Cells can be treated with our therapy in a laboratory, and tested before being transfused back into the patient.

We will develop a pipeline to rapidly design, screen and test gene editing strategies for T cells and/or HSC for primary immune deficiencies associated with defects in EBV handling.  

Members of our multi-disciplinary team will use their local clinical resources and NHS Genomic Medicine Service data to identify patients with pathogenic variants of interest, and to access relevant clinical material for ethically approved functional and safety studies.

We will co-develop the design and testing pipeline with UC Berkeley and IDT.  In collaboration with Newcastle, selected gene editing strategies will undergo functional validation and safety testing in primary blood cells.  With UCL, we will examine the potential for scaling towards clinical manufacture and engage with regulators to determine the required pre-clinical data package required for future trials.  

As part of the project, we intend to involve patients and the public to better understand their research priorities and perceptions of tolerable risk.  In this way, we will generate a template that can be applied to other blood and immune disorders and have broader relevance to acceptable safety thresholds for gene editing.