On February 10, 2023, Hemogen Theropeutic Co.Ltd (Hemogen, a subsidiary of BGI), Thalassemia Diagnosis and Treatment Innovation Research Center of Nanfang Hospital, Southern Medical University(Southern Medical University), 923 Hospital jointly initiated a project on February 10, 2023. The project, titled “Clinical Study on the Safety and Efficacy of Autologous Hematopoietic Stem Cell Injection (HGI-002) Transduced with Lentivirus Encoding Human α-Globin for the Treatment of Transfusion-Dependent α-Thalassemia,” has successfully seen its first patient weaned off transfusion dependency. The patient, nicknamed Xiao Wei, received a transfusion of the transduced autologous hematopoietic stem cells on April 7, 2023. Neutrophil engraftment occurred on day 16 post-transfusion, platelet engraftment on day 17, and by day 26, the patient was independent of transfusions. This marks the world’s first case of transfusion-dependent α-thalassemia successfully treated with gene therapy, leading to transfusion independence.

Dr. Chao Liu from Hemogen explained: HGI-002 Injection is a gene therapy based on autologous hematopoietic stem cells. By extracting patient's own hematopoietic stem cells and using lentivirus to reintroduce functional α-globin gene ex vivo, HGI-002 Injection helps to restore the ratio of α- and β-globin and to restore hemoglobin function in order to help patient achieve transfusion independence. HGI-002 Injection is another important research product of HGI, following the first-tier product HGI-001 injection (Successfully freed 5 patients with transfusion-dependent β-thalassemia from the dependence on blood transfusions.).

Prof. Xiangmin Xu from Southern Medical University explained: α-Thalassemia is divided into four grades: severe, intermediate, mild, and silent. Generally, severe α-thalassemia results in intrauterine or postnatal death, while mild and silent α-thalassemia only cause mild anemia or no anemia. Intermediate α-thalassemia (also known as hemoglobin H disease) can be either transfusion-dependent or non-transfusion-dependent. The severity of anemia in the future cannot be determined before or immediately after birth. It is one of the most difficult type of thalassemia to choose in the prevention and control of thalassemia and the most common type of thalassemia in Asian countries. There are 200,000 to 250,000 patients in southern China, of which approximately 15% are transfusion-dependent. The proportion of transfusion-dependent cases in patients with non-deletional hemoglobin H disease is about 30%.

Prof. Xinhua Zhang from 923 Hospital explained: Previously, we have cooperated with three domestic technology companies to free nine transfusion-dependent β-thalassemia patients from blood transfusion dependence through gene therapy using gene editing. Cooperating with Hemogen to treat transfusion-dependent α-thalassemia through lentivirus-mediated gene therapy is a new challenge. Xiao Wei's successful liberation from blood transfusion dependence is another breakthrough in thalassemia treatment, which will benefit more thalassemia patients.

Gene therapy using gene editing for treating transfusion-dependent β-thalassemia uses CRISPR/cas9 gene scissors technology to reactivate the normal, silenced γ-globin expressed during fetal development, thereby expressing the patient's own fetal hemoglobin, removing the pathological basis of excessive α-tetramer on the red blood cell membrane in β-thalassemia patients, improving the stability of the red blood cell membrane, and achieving or approaching the normal lifespan of red blood cells, correcting the anemia state.

α-globin plays a crucial role in hematopoiesis during fetal development, while β-globin is almost absent from fetal hematopoiesis. Therefore, gene therapy for α-thalassemia cannot adopt the same strategy as that for β-thalassemia. In addition, β-thalassemia is caused by mutations or deletions in the β-globin gene, while α-thalassemia is mainly caused by deletions or compound mutations in the α-globin gene, leading to functional defects in the α-globin gene. Currently, there is no mature method globally to repair α-globin gene deletions using CRISPR/cas9 gene scissors technology.

In order to achieve the vision of "No Thalassemia in the World" as soon as possible, BGI has been committed to screening and rescuing thalassemia for many years, strengthening thalassemia prevention and control through various aspects such as people's livelihood, scientific research, and public welfare, and helping people to get rid of poverty through advanced gene technology. Both thalassemia prevention and control and the eradication of thalassemia are indispensable. Both α-thalassemia and β-thalassemia can be cured, and "No Thalassemia in the World" is worth looking forward to.