#China #Shanghai #Sickle Cell #CorrectSequence #CS-101

Revolutionary Advances in Sickle Cell Disease Treatment

CorrectSequence Therapeutics Co., Ltd., a cutting-edge biotechnology firm, has marked a major milestone in the treatment of sickle cell disease (SCD) with its innovative base-editing therapy, CS-101. Recently, the company announced favorable outcomes from the therapy's application on its first patient — a 21-year-old woman hailing from Nigeria. Before her treatment, she frequently encountered vaso-occlusive crises, a common complication associated with SCD.

The Transformation Journey

After undergoing treatment with CS-101, this patient has reported an impressive transformation. Over a six-month period following her therapy, she remained crisis-free and maintained an overall good health status. The treatment, which was part of an investigator-initiated trial conducted in partnership with the First Affiliated Hospital of Guangxi Medical University, yielded significant results including a substantial rise in fetal hemoglobin (HbF) levels and a noteworthy decline in sickle hemoglobin (HbS).

After six months, her HbF-to-HbS ratio stabilized at an impressive 6.5, and her total hemoglobin consistently exceeded 120 g/L. This breakthrough marks a pivotal moment as it represents the first documented clinical treatment of SCD in China utilizing base editing technology.

Understanding Sickle Cell Disease and the Need for Innovative Therapies

Sickle Cell Disease, classified under hemoglobinopathies, affects approximately 400,000 newborns each year globally. The condition results from mutations in the β-globin gene, leading to misshapen red blood cells that can create numerous health complications such as chronic anemia and organ damage. Treatments available today primarily focus on symptomatic relief rather than offering a cure, which points to a critical need for innovative solutions addressing the root cause of the disease.

Traditional methods like blood transfusions may alleviate symptoms but do not eradicate the disease. Moreover, although hematopoietic stem cell transplantation can yield curative outcomes, challenges regarding donor matching often hinder accessibility. In contrast, gene-editing technologies such as base editing present a groundbreaking alternative. They can facilitate the activation of fetal hemoglobin in a patient’s own blood cells, eliminating reliance on a donor and providing a more viable treatment path.

The Technology Behind CS-101

CS-101 employs a precise base editing technique developed on the tBE (transformer base editor) platform, which allows for accurate targeting and modification of the regulatory elements of the γ-globin genes. This process mimics naturally occurring genetic variations in individuals with permanently elevated fetal hemoglobin levels. Such functionality results in an increase in HbF, which prevents sickling of the red blood cells and significantly reduces hemolysis.

During the investigator-initiated trial, the patient began with a baseline hemoglobin level recorded at 67.3 g/L. Following her treatment in February 2025 with CS-101, a swift hematopoietic recovery was observed. Neutrophil contributions were noted at just 13 days post-treatment, and platelet counts exceeded 50×10⁹/L within 21 days. Remarkably, her HbF levels surged from 4.4% to 34.6% within one month and stabilized above 60% shortly thereafter, with HbS remaining subdued below 40%. Notably, no vaso-occlusive crises or adverse events related to the treatment emerged.

A Safer and More Efficient Intervention

CS-101 shows a favorable profile compared to conventional CRISPR/Cas9 therapies; it provides a more efficient recovery of hematopoiesis and boasts a significantly enhanced HbF-to-HbS ratio. Importantly, it lacks the risks associated with large DNA deletions, chromosomal rearrangements, or off-target effects, making it a promising candidate for clinical use.

As of now, CS-101 has treated nearly 20 patients with β-thalassemia or SCD in clinical trials, with one patient having achieved over 22 months of transfusion-free status. This positions CS-101 as potentially the foremost gene-editing therapy designed for β-hemoglobinopathies.

Future Directions and Global Developments

Following the successful completion of the Phase I trial for β-thalassemia, where all patients achieved transfusion independence, CorrectSequence Therapeutics is eager to advance to pivotal Phase II/III trials. Global recruitment for trials involving both SCD and β-thalassemia is currently underway. The company remains committed to progressing CS-101 — a groundbreaking, China-initiated gene-editing treatment — to deliver safe, effective, and widely accessible therapies to those grappling with severe hemoglobin disorders worldwide.

About CorrectSequence Therapeutics

Originating from ShanghaiTech University, CorrectSequence Therapeutics is devoted to harnessing state-of-the-art gene-editing technologies to transform the lives of individuals facing severe health conditions. The company has created multiple advanced base-editing systems designed to maximize precision, minimize off-target effects, and improve in vivo editing efficiencies. Correctseq's expansive pipeline aims to cover a wide array of conditions, underscoring the potential of its innovative therapeutics. For further details, please visit www.correctsequence.com.