Breakthrough in Sickle Cell Disease Treatment: CS-101 by CorrectSequence Therapeutics

Introduction In a groundbreaking development in the field of genetics and medicine, CorrectSequence Therapeutics Co., Ltd. has made significant strides with its gene editing therapy, CS-101, for the clinical treatment of sickle cell disease (SCD). Recently, the company announced the successful treatment of a 21-year-old female patient from Nigeria, marking a historic first in China utilizing their pioneering transformer Base Editing (tBE) technology. ### Patient Background The patient, who had endured recurrent vaso-occlusive crises, is now reportedly crisis-free and in good health six months following her treatment with CS-101. This achievement showcases the potential of gene editing not just as a scientific endeavor but as a transformative approach to treating severe genetic disorders like sickle cell disease. ### Study Details The breakthrough results emerged from an investigator-initiated trial (IIT) conducted in collaboration with The First Affiliated Hospital of Guangxi Medical University. The study demonstrated a substantial and lasting increase in fetal hemoglobin (HbF) levels, alongside a significant reduction in sickle hemoglobin (HbS) levels. Six months post-treatment, the patient's HbF to HbS ratio stabilized at 6.5-5, with overall hemoglobin consistently exceeding 120 g/L. Importantly, there were no reported vaso-occlusive crises during the six-month observation period, allowing the patient to resume her daily activities without the debilitating symptoms previously experienced. ### Understanding Sickle Cell Disease Sickle cell disease is one of the most common monogenic disorders worldwide, affecting approximately 7% of the global population, leading to around 400,000 newborns affected each year. Characterized by mutations in the β-globin gene, SCD causes red blood cells to become rigid and sickle-shaped, resulting in chronic anemia, painful crises, and a heightened risk of infections and organ damage. Existing treatments primarily focus on alleviating symptoms, lacking curative options. Hematopoietic stem cell transplantation (HSCT) is the only known potential cure but is limited by the availability of suitable donors. ### The Promise of Base Editing CS-101 employs advanced gene editing technology that targets β-globinopathies by modifying regulatory elements in the promoter of γ-globin genes (HBG1/2). This innovative approach mimics naturally occurring single-nucleotide variants in individuals with hereditary persistence of fetal hemoglobin. By reactivating γ-globin expression, CS-101 facilitates the production of functional HbF, which can prevent red blood cell sickling and reduce hemolysis. In the clinical trial, this patient's baseline hemoglobin was recorded at 67.3 g/L. Remarkably, after CS-101 administration in February 2025, the patient experienced rapid hematopoietic recovery with neutrophil engraftment occurring within 13 days and platelet counts exceeding 50 x 10⁹/L within 21 days. Following the treatment, her HbF levels soared from 4.4% to 34.6% within one month, and remained above 60% since the third month, keeping her HbS below 40%. No vaso-occlusive crises or adverse treatment events were recorded, highlighting the safety of the approach. ### Comparative Effectiveness CS-101 stands out from traditional CRISPR/Cas9-based therapies by offering efficient hematopoietic recovery and a more favorable HbF to HbS ratio without the risk of large DNA deletions, chromosomal rearrangements, or off-target mutations. To date, almost 20 patients with β-thalassemia or SCD have been treated with CS-101 in clinical trials, with the first β-thalassemia patient maintaining a transfusion-free status for over 22 months. This positions CS-101 as a leading gene editing therapy, potentially the first base editing treatment approved for β-globinopathies. ### Future Directions The Phase I study of CS-101 targeting β-thalassemia has been successfully completed, enabling all patients to become transfusion-independent. Currently, pivotal Phase II/III studies are set to commence, with global recruitment ongoing for SCD and β-thalassemia trials. CorrectSequence Therapeutics aims to further advance CS-101 as a premier gene therapy developed in China, aspiring to provide safe, effective, and accessible treatments for patients with severe hemoglobin disorders globally. ### About CorrectSequence Therapeutics Founded at ShanghaiTech University, CorrectSequence Therapeutics focuses on leveraging innovative gene editing technologies to enhance the lives of those suffering from serious diseases. The company has developed several cutting-edge base editing systems providing exceptional precision, minimizing off-target effects, and enhancing in vivo editing efficiency. Correctseq's mission is to discover, develop, manufacture, and commercialize curative genetic medicines across a range of conditions, with a robust pipeline including genetic disorders, metabolic diseases, and cardiovascular conditions already advancing into clinical development. For further information, please visit CorrectSequence Therapeutics. ### Acknowledgments Special thanks to The First Affiliated Hospital of Guangxi Medical University, ShanghaiTech University, and Shanghai Clinical Research and Trial Center for their collaboration in this groundbreaking study.