EBMT 2024 | Autologous gene editing using the CRISPR system to treat primary immunodeficiency disorders

So bone marrow transplant is curative for many primary immunodeficiencies. But that obviously carries a risk of graft-versus-host disease. And you need to have a suitable donor. So autologous gene therapy where you take the patient’s own hematopoietic stem cells and replace them after genetically engineering them outside of the body, is a much better, safer treatment for these disorders. And there are really lots of new, exciting technologies which we can use to perform that genetic correction now. So I’m going to be talking about gene editing technologies, variants of the CRISPR system. So kind of the first iterations of the CRISPR system, which are the non-homologous repair pathway and homology-directed repair, and then the newer CRISPR mechanism, so base editing, prime editing, transpose based systems, and how we can use those to form effective gene therapy for primary immunodeficiencies.

Some of the biggest challenges, though, for gene therapy in this group of rare disorders is actually getting these therapies for to patients. So we already have many effective therapies which have demonstrated proof of concept preclinically. But in the rare disease context, it’s difficult to translate those into the clinic. There’s not the same commercial interest in rare diseases. So that’s a challenge that myself and many other people are working on to try and find ways of getting these therapies to patients.