The world's first CRISPR gene editing treatment for beta 0/beta 0 was successful at the Nanjing 2020 BPIT Conference.

July 22, 2020 / emedclub news / - - on July 21, 2020, bpit 2020 was held in emaker At the conference of biological innovative drug technology, Dr. Wu Yuxuan from Shanghai bangyao Biotechnology Co., Ltd. and East China Normal University announced for the first time that the clinical trial of "clinical study on the safety and effectiveness of gamma globin reactivated autologous hematopoietic stem cell transplantation in the treatment of severe β - thalassemia" was carried out in cooperation with Xiangya Hospital of Central South University for the first time It is the first time to treat thalassemia (thalassemia) by gene editing technology, and it is also the first successful case of severe thalassemia treated by CRISPR gene editing technology in the world. In this clinical study, hematopoietic stem cells (HSCs) were isolated from patients. By CRISPR / cas9 gene editing technology, gene editing was carried out at specific gene sites in HSC, and then the edited HSC was autotransplanted to make the hemoglobin level of patients reach the normal range and completely get rid of blood transfusion dependence Lai.the two patients, 7 and 8 years old, were blood transfusion dependent patients with severe beta thalassemia (β 0 / β 0 and β 0 / β + respectively). The frequency of blood transfusion before treatment was about 15-20 days of two units of red blood cells.before treatment, HSC were mobilized and collected, and HSC was isolated and gene edited by bangyao bio, and then transferred back to the patient.after gene editing HSC transplantation, both patients successfully achieved hematopoietic stem cell implantation and hematopoietic reconstitution.after transplantation, fetal hemoglobin (HBF) in the two patients began to rise significantly at 1 month after transplantation. At 60 days of follow-up, the levels of HbF rose to 76 g / L and 97 g / L, respectively. The data of 75 days follow-up showed that the total hemoglobin of the two patients reached 129 g / L and 115 g / L respectively, and they had got rid of blood transfusion dependence.at present, the follow-up of two patients is still in progress. Thalassemia is a single gene genetic disease with the widest distribution and the most involved population in the world. According to the data of China's blue book on prevention and treatment of thalassemia (2015), there are about 30 million people carrying thalassemia gene in China, involving 100 million families, and about 300000 patients with moderate to severe thalassemia At a rate of about 10% per year.due to the deletion or mutation of HBB gene, the patients with β - thalassemia can not encode β - globin or produce defective β - globin, so they can not form normal tetramer (adult hemoglobin, Hb A) with α - globin to carry oxygen, resulting in severe anemia and related complications.according to statistics, about 60000 infants are born with severe transfusion dependent beta thalassemia (TDT) every year, with more than 200000 patients worldwide.at present, the routine treatment of thalassemia is regular blood transfusion and adequate iron removal.many TDT patients experience severe complications and organ damage due to potential disease and iron overload.in addition, the traditional lifelong blood transfusion and iron removal therapy costs about 4.8 million yuan in a lifetime, which is a heavy burden that most families cannot bear.} image source: medical news today most of the children with severe diseases die within 5 years of age without the expensive treatment of frequent blood transfusion and iron removal.at present, there is no cure other than allogeneic hematopoietic stem cell transplantation.in human embryonic stage, hemoglobin is mainly composed of gamma globin (HbG gene coding) and alpha globin to form tetramer (fetal hemoglobin, HbF).HbG expression was silenced after birth, and HBB gene began to express to produce β - globin, which replaced γ - globin and α - globin to form tetramer, namely adult hemoglobin HbAA.clinical studies have found that there is no severe clinical phenotype of β - thalassemia in some HBB gene deficient populations, suggesting that reactivating fetal HbG expression and obtaining a higher level of HbF in thalassemia patients can alleviate the symptoms of thalassemia patients and even completely cure them.in this clinical study, CRISPR / cas9 gene editing technology was used to edit genes at specific genomic sites in HSC to activate HbG expression of patients, so as to greatly increase the content of gamma globin in red blood cells and make the hemoglobin level reach the normal range. Dr. Wu Yuxuan, a bioscientist of bangyao, said: "gene editing technology for thalassemia is a cutting-edge technology in the field of global gene therapy. At present, only CRISPR therapeutics in the United States reported successful cases in 2020. Two patients with β 0 / β + got rid of blood transfusion dependence for 5 and 15 months after receiving treatment. one of the patients treated by bonyao bio is β 0 / β 0 thalassemia with complete deletion of β globin gene. Compared with the clinical trial in the United States, this treatment is more difficult. overcoming the difficulty of β 0 / β 0 thalassemia means that all transfusion dependent thalassemia can be cured through this treatment strategy. "on January 13, 2020, zynteglo, a blue bird beta thalassemia gene therapy, was launched in Germany. zynteglo is a new type of gene therapy. In this therapy, hematopoietic stem cells are isolated from patients, and the modified β - globulin gene which can perform normal function is inserted into the patient's own hematopoietic stem cells by virus vector, and then the gene is transferred back to the patient. the therapy does not introduce gene editing technology, but the β - thalassemia therapy of bangyao biological Co., Ltd. can activate the HbG expression of patients by introducing CRISPR / cas9 gene editing technology into the treatment, so as to make the treatment of β - thalassemia more accurate and play a greater curative effect. in addition, zynteglo has a price of 1.575 million euro (about 12.1 million yuan), which is worthy of its name as the second most expensive drug in the world. Compared with zynteglo, the treatment scheme adopted by bonyao bio is more efficient, convenient and safe, and its cost is greatly reduced. It is expected to become a therapy more beneficial to the public. focusing on the field of gene therapy, bangyao has been making breakthroughs and upgrading, and the pharmaceutical field represented by gene therapy and cell therapy is facing unprecedented opportunities, which is a major breakthrough direction in the pharmaceutical field in the next decade. bangyao biological has always been committed to developing innovative drugs for gene therapy. Since its inception, it has established an international strategy of "based in China, distributing around the world and benefiting the world", so as to meet the rapid growth of the medical market in China and the world, and bring good news to those patients who are in urgent need of revolutionary gene therapy. bangyao has differentiated competitive advantages in product line selection and technology platform. Aiming at the core pipeline product - gene therapy - thalassemia, bangyao biology overcame the industry barriers, not only fully mastered the gene editing technology, but also deeply understood the hematopoietic stem cell editing strategy, so as to continuously optimize the process, so as to meet the key problems in the treatment process of gene editing hematopoietic stem cells Solution. in the previous research, bangyao bioscientists team has made a series of breakthroughs in the field of gene editing tool development and gene therapy for thalassemia: the use of gene editing technology to re open the expression of fetal gamma globin instead of defective beta globin is likely to become one of the treatment options for thalassemia patients. on March 25, 2019, Dr. Wu Yuxuan, a bioscientist of bangyao and East China Normal University, published a paper in nature medicine. It was found that targeting Bcl11A enhancer with gene editing technology would re open the expression of γ - globin and replace the defective β - globin, which is expected to achieve the goal of eradicating such diseases. on January 8, 2020, bangyao biological scientists, Professor Liu Mingyao and Professor Li Dali of East China Normal University published a paper in cell research. By establishing an ultra efficient gene editing technology system in hematopoietic stem cells and simulating the natural mutation of gamma globin promoter in some people, fetal hemoglobin HbF can be reactivated. on March 17, 2020, Dr. Wu Yuxuan, a bioscientist of bangyao and East China Normal University, made another breakthrough, and published a paper in nature medicine confirming that the new generation of single base editing technology is expected to completely eradicate a series of genetic diseases caused by β - globin mutation, and it is possible to completely eradicate such diseases. on May 11, 2020, bangyao bioscientist, Professor Liu Mingyao and Professor Li Dali of East China Normal University published a paper in nature cell biology, and developed a series of novel cytosine base editors with ultra-high activity (named: hycbe). Hycbe has higher editing activity and wider editing window, which has greater advantages for the treatment of β - hemoglobin disease. on June 1, 2020, a team of biological scientists from bangyao, Professor Liu Mingyao and Professor Li Dali of East China Normal University published a paper in Nature Biotechnology, which developed a new type of bifunctional base editor (named as: A & amp; a; a & amp; B, a & amp; B; a & amp; a; a & amp; a; a & amp; a; a; a & amp; a; a; a; a; a; a; a; a; C-bemax) breaks the limitation of the existing base editor and develops a new type of bifunctional base editor, which provides a new platform for basic research and treatment of genetic diseases such as β - thalassemia. Mr. Xi Zaixi, CEO of bangyao biology, said: "the advent of the era of gene medicine has brought new understanding and new ideas to the disease itself and cure the disease. bangyao biological has always been shouldering the mission of 'leading innovation with gene editing, developing breakthrough therapy and benefiting all mankind', and strives to successfully implement the gene editing tool representing the top technology of biological industry in the research and treatment of diseases. among them, thalassemia is a single gene genetic disease with the widest distribution and the most people involved in the world. China is a country with more thalassemia diseases. This clinical study makes gene therapy based on gene editing hopeful to become a new clinical treatment scheme for patients with β - thalassemia, which can not only bring lifelong health to thalassemia patients, but also greatly reduce blood bank pressure. "at present, bangyao biology, in close cooperation with East China Normal University, has built an innovative and efficient gene editing platform, and is focusing on clinical transformation around these independent technologies.  ▲ Based on the strategy of gene editing technology for the treatment of thalassemia (from the official website of bangyao Biology) about bangyao biotechnology Shanghai bangyao Biotechnology Co., Ltd. is committed to becoming a global leading gene cell pharmaceutical company in the era of new commercial civilization. With the mission of "leading innovation with gene editing, developing breakthrough therapy and benefiting all mankind", bangyao biotechnology relies on its independent R & D center and East China Normal University The Shanghai gene editing and cell therapy research center jointly built by the university has produced 105 patent achievements in the past five years. Five projects have carried out IIT trials in eight famous hospitals, three of which have entered the ind application stage, and 12 high-level academic papers have been published in international well-known journals such as Nature Biotechnology and nature medicine. bangyao biological has built three technical platforms of gene editing, cell therapy and gene therapy, and has a 6000 square meter GMP pilot base and an operation team of nearly 100 people, which strongly guarantees the rapid transformation and application of innovative research results. through patient demand and clinical feedback, bangyao bio continuously promotes the rapid update and iteration of R & D products. with an open, shared and win-win attitude, we will work with global innovative biopharmaceutical ecological chain enterprises to accelerate the transformation and implementation of innovative drugs, so as to benefit the global patients with genetic diseases and malignant tumors! Recent hot reports of Meditech