CRISPR gene editing technology has made significant progress in the treatment of patients with severe beta-thalassemia

Thalassemia is one of the most widely distributed and affected single-gene genetic diseases in the world. In China, some southern provinces are areas with a high incidence of thalassemia, and the carrying rate of thalassemia genes in the population can even be as high as 20% above. Beta-Thalassemia is one of the most predominant types of thalassemia, and treatment progress has been slow over the past few decades. Hematopoietic stem cell transplantation has long been the only cureBeta-Methods of thalassemia，However, allogeneic transplantation has many short-term and long-term comorbidities, is not an ideal cure, More effective and safer treatment methods are urgently needed. Moreover, a large number of patients with thalassemia cannot receive transplantation due to poor physical condition toleration and high incidence of autoantibodies.autologous hematopoietic stem cells“Genetic correction”Later transfusion into patients can overcome the high comorbidities of allogeneic transplantation and the source of donors, and advances in gene editing technology are making this treatment strategy a reality.

Professor Fu Bin of Xiangya Hospital of Central South UniversityWithShanghai Bangyao Biotechnology Co., Ltd.“Bangyao Biotech”）A collaboration IIT（Investigator-initiated clinical studies), A case acceptanceCRISPRGene Editing Therapyβ0/β0Children with severe thalassemia are now free from blood transfusion dependence3Year，According to the research team， This is also“The world's first”ReportedCRISPRGene Editing Therapyβ0/β0Successful clinical outcomes in children with severe thalassemia.With this innovative gene therapy, thalassemia patients are expected to achieveOne treatment, a lifetime“Cure”effect.

How Gene Therapy Will Benefit a Wide Range of Patients With Hereditary Blood Disorders？ As the First Diseases to Benefit from This Emerging Technology， PresentBeta-What are the strategies and latest progress of thalassemia gene therapy？ Can gene therapy gradually become the mainstream choice for thalassemia treatment？As one of the leading experts in hereditary blood diseases, Professor Fu Bin shared his clinical experience, innovative treatment research results, and insights on treatment development trends.

Professor Fu Bin said that halalasemia is actually an early apoptosis of red blood cells in the bone marrow cavity caused by abnormal globin genes, that is, early hemolysis, and the diversity of globin gene mutations leads to multiple types of thalassemia. Common clinical thalasemia includes:α-Thalassemia andBeta-The two types of thalassemia are caused byα,betaglobin peptide chain synthesis disorders.For the treatment of thalassemia, we have gone through several changes of the times， Simple blood transfusion+There is room for improvement in iron deprivation therapy, both in terms of clinical efficacy, quality of life and duration of survival, safety, and patient compliance.Different gene therapy modalities are expected to correct genetic abnormalities at the source.

Current gene therapy strategies for thalassemia include alternative therapy, compensatory therapy, and gene repairSpecifically：

• Gene replacement therapy refers to the replacement of a patient's abnormal gene with normal genes.
• Because the hemoglobin gene locus is very complex, its regulatory mechanism has not yet been thoroughly studied, so scientists have thought of a strategy to treat the disease by promoting fetal hemoglobin, which is usually expressed three to six months after the fetus is born, gradually shut down, resume expression, and then recover, which is a compensatory strategy. This strategy is also one of the treatment strategies that many companies at home and abroad are currently paying attention to.
• Gene repair strategy refers to the use of gene editing or recombination to repair related genes in situ, which is also the most ideal gene therapy strategy at present.

With these three strategies, we can completely replace the abnormal genetic system.From the perspective of long-term sustained efficacy, treatment safety, and risk of complications, this may be a holistic replacement gene therapy.betaOptimal treatment strategies for thalassemia， are theoretically more likely to help patients achieve their desired status.

In addition to gene therapy, innovative drugs for the treatment of thalassemia, such as small molecule drugs for red blood cell regulation and erythropoietic drugs, are also emerging.However, so far, I think the most stable and reliable treatment for thalassemia may be gene therapy.

At present, the research therapies developed by Professor Fu Bin and Bangyao Biotech mainly use the gene editing system to genetically modify the patient's hematopoietic stem cells, and then reinfuse the modified hematopoietic stem cells into the patient's body, reconstruct the modified cell population through self-renewal and differentiation, so as to achieve the purpose of treating hematological diseases. The gene editing therapy of hematopoietic stem cells developed by them is more efficient, convenient and safe, has the advantages of good targeting, high safety, wide range of action, and significant therapeutic effect, and can greatly reduce costs compared with existing technologies.

Professor Fu Bin

Deputy Chief Physician, Department of Hematology, Xiangya Hospital, Central South University

★ Vice Chairman of the Rare Disease Professional Committee of Hunan Genetics Society

★ Chairman of the Bone Marrow Exhaustion Disease Alliance of Xiangya Hospital of Central South University

★ Hunan Bone Marrow Exhaustion Disease Collaboration Group

★ Member of the Hematologist Branch of the Hunan Medical Doctor Association

★ Member of the Hematology and Oncology Committee of the Chinese Anti-Cancer Association

★ Member of the Expert Committee of the China Working Group on Myelodysplastic Syndromes and Myeloproliferative Tumors