UCLA Researchers Develop Potential Lentivirus-based Gene Therapy for Alpha Thalassemia

LOS ANGELES-Sep 18, 2025— A team of researchers at UCLA, led by gene therapy pioneer Dr. Donald Kohn, has developed a promising new stem cell gene therapy that could be a one-time, curative treatment for alpha thalassemia major (ATM), a severe inherited blood disorder. The findings were published in the journal Cell Reports Medicine. This breakthrough addresses a new medical challenge created by successful in-utero blood transfusions, which have allowed children with this previously fatal diagnosis to be born. However, these children face a lifetime of health issues and specialized care.

A Personalized Approach to Treatment

The new therapy is a form of personalized medicine that uses the patient’s own blood stem cells, eliminating the need for a matched donor and the associated risks of a bone marrow transplant, such as graft versus host disease (GVHD). The process, known as ex vivo gene therapy, involves collecting a patient’s own blood stem cells (HSPCs). These cells are then transduced using a viral vector, specifically a lentivirus, to deliver the missing α-globin gene (HBA2) into them.  Finally, the corrected cells are returned to the patient after myeloablative conditioning. In preclinical studies, this approach successfully restored normal α-globin protein production in patient cells, enabling the creation of functional hemoglobin.

“The idea of a blood stem cell gene therapy is to fix the disease at the DNA level,” said first author Eva Segura. According to Dr. Kohn, if enough cells can be corrected, the results should be lifelong. This research was sparked by a collaboration with Dr. Tippi MacKenzie, a pediatric surgeon who reached out to the UCLA team. Dr. Kohn has a history of successfully developing similar gene therapies, including a cure for ADA-SCID, a severe immune deficiency.

The Science Behind the Breakthrough

Thalassemias are a group of blood disorders caused by mutations in the genes that produce the polypeptide chains forming hemoglobin (HbA). In ATM, the most severe form, all four α-globin genes are deleted, drastically limiting hemoglobin synthesis. This leads to severe anemia, multi-organ damage from iron overload, and historically, death in utero. The new lentiviral vector is engineered to deliver the HBA2 gene under optimized transcriptional control, using elements from the β-globin gene to ensure proper expression. This approach builds on the success of similar gene therapies for β-thalassemia and sickle cell disease, which have recently gained FDA approval.