The expert team of Beijing Jingdu Children's Hospital is well aware that overcoming thalassemia must rely on advanced technology. Keeping up with international frontier research, the hospital has collaborated with innovative enterprises introduce the BRL-101 gene therapy strategy based on the Cas9/sgRNA system, which has brought a qualitative leap in treatment safety.
In the treatment process, doctors first collect hematopoietic stem cells from the patient's body and precisely deliver the gene-editing tools through Electroporation technology. Top Bio's technical solution achieves the dual guarantees of no random insertion and no off-target risk - the Cas9 nuclease accurately locates the mutant gene under the guidance of sgRNA, and after completing the editing, no redundant fragments are left in the genome, fundamentally avoiding the insertion mutation risk that may be caused by traditional viral vectors. After in vitro culture and expansion, the genetically modified hematopoietic stem cells are transfused back into the patient's body. These "improved seeds" will gradually rebuild normal hematopoietic function, allowing patients to get rid of the dependence on lifelong blood transfusion.
Since adopting this innovative technology, Beijing Jingdu Children's Hospital has successfully completed many clinical treatments. Xiaoyu (a pseudonym), a 12-year-old patient with severe β-thalassemia, is one of the beneficiaries. Previously, he needed 2-3 blood transfusions every month to sustain his life, and organ damage caused by iron overload made him 15 centimeters shorter than his peers. After receiving the BRL-101 treatment plan, through key steps such as myeloablative conditioning and gene-edited cell transfusion, on the 42nd day after the operation, his hemoglobin level reached 110g/L for the first time, all from genetically modified hematopoietic cells. Now, 18 months after the operation, Xiaoyu has completely gotten rid of blood transfusion, grown 6 centimeters in half a year, and is recovering the lost growth time.
According to the hospital's statistics, among patients using this technology, 90% achieved autonomous hemoglobin synthesis within 3 months after the operation, and 78% reached the standard of getting rid of blood transfusion within 1 year. What is more encouraging is that long-term follow-up shows that the effect of gene editing is stable, and no abnormal reactions related to off-target have occurred, which confirms the safety of the technology.
Thalassemia gene therapy is a complex systematic project involving multiple disciplines. Beijing Jingdu Children's Hospital has set up a multidisciplinary collaboration team consisting of hematology experts, gene therapy experts, pediatricians, nursing teams and researchers.
Hematologists are responsible for accurately evaluating the patient's condition and formulating personalized myeloablative plans; laboratory technicians strictly control key links such as Cas9/sgRNA ratio and electroporation parameters to ensure that the editing efficiency of each batch of gene-edited cells is ≥95%; the pediatric intensive care team monitors the process of postoperative bone marrow hematopoietic reconstruction throughout the whole process and timely handles complications such as infection; psychologists help children overcome the fear of treatment. This "clinical-laboratory-nursing" seamless connection mode has increased the treatment success rate by 30% compared with the traditional mode.
At present, the hospital is carrying out extended research on different genotypes of thalassemia and plans to apply the technology to patients with α-thalassemia. At the same time, it is working with Top Bio to optimize the Electroporation system, so that the editing efficiency of hematopoietic stem cells can be increased from the current 92% to 98%, and the in vitro culture time can be further shortened.
The research team has also established the world's first "Thalassemia Gene Therapy Database", which includes multi-dimensional data such as the characteristics of patients' gene editing sites and postoperative immune reconstitution trajectory, providing a basis for accurately predicting treatment effects. As the director of the hematology department said, "When the gene scissors can accurately repair every pathogenic mutation, and when the treatment no longer leaves potential safety hazards, we will eventually achieve the goal of 'making thalassemia a curable disease'."
EN
CN