Gene Therapy for β-Hemoglobinopathies: From Discovery to Clinical Trials
Beta thalassaemia is an inherited disorder that impairs the production of haemoglobin, the blood protein responsible for transporting oxygen. Patients with beta thalassemia need regular blood transfusions to replace the missing haemoglobin, and lifelong pharmacological treatments to reduce the iron excess caused by transfusions.
Gene therapy consists of the following steps:
- Stem cells are collected from a patient’s blood and functional haemoglobin genes are added to their DNA via a viral vector.
- Abnormal stem cells are cleared from patient’s body by chemotherapy and the functional gene-edited stem cells are infused back sustaining a long-term production of working haemoglobin.
However, some patients could face a high risk of morbidity/mortality due to graft versus host disease or graft failure, while a majority of patients may not be able to have such HLA match-related donors. Another burden of gene therapy is that it is still inaccessible in developed as well as developing countries in which most of beta thalassaemia patients live due to the enormous cost of the procedure.
The biggest challenge for the scientific community is to find ways to make this curative approach an accessible and affordable one for every patient in the world. As of now, one ambitious, but foreseeable, goal is to evolve these gene therapy techniques to an in vivo delivery mode, where systemic injection of a vector or editing reagents effectively corrects the haemoglobin gene in hematopoietic stem and progenitor cells in situ and therefore decrease the cost.
