In a breakthrough for gene therapy, the international academic journal Nature has published a landmark clinical study detailing the successful use of a novel base-editing drug to treat β-thalassemia.

Jointly conducted by ShanghaiTech University, the First Affiliated Hospital of Guangxi Medical University, Fudan University, and CorrectSequence Therapeutics, the early-stage clinical trial of the base-editing drug CS-101 injection reports that all treated transfusion-dependent patients rapidly achieved transfusion independence and regained healthy hematopoietic function.

A pressing unmet medical need

Stem cell transplantation could be a rapid and effective way to restore hemoglobin production in individuals with the blood disorder β-thalassaemia. The treatment, presented in a phase 1 clinical trial, could reduce dependence on blood transfusions in some individuals with the disease in the future, although further trials are needed to confirm these findings.

β-Thalassaemia is a blood disease characterized by an inability to correctly synthesize the β-subunit of hemoglobin, which can lead to anemia and defects in the production of red blood cells. The defective subunit synthesis can be caused by more than 350 different known mutations in the β-globin gene (HBB) and is primarily treated by regular red blood cell transfusions, which can be arduous for patients.

Fetal hemoglobin (HbF, which is expressed in fetuses but declines after birth) lacks a β-subunit; thus, increasing its levels may have potential as a long-term treatment for β-thalassaemia. Elevating HbF levels could be achieved through stem cell therapies; however, clinical trials to test this approach have been lacking.

Jia Chen and colleagues present the results of a phase 1 clinical trial in an article published in Nature, in which five patients with severe β-thalassaemia received a one-time infusion of their own modified stem cells. The authors used base editing to modify specific binding sites and reactivate the gene responsible for HbF production. The participants ceased regular red blood cell transfusions within one month after the stem cell infusion.

Total hemoglobin and HbF concentrations of 12.4 and 11.5 grams per deciliter of blood were observed at three months post infusion, suggesting successful production of functional hemoglobin. These levels were sustained or improved upon throughout the follow-up period, which lasted for a median of 23 months.

Further clinical research will be needed to validate the results of this treatment in a larger cohort and over a longer period. However, these results suggest that a one-time stem cell infusion could assist some patients in regaining independence from reliance on transfusions.

At present, allogeneic hematopoietic stem cell transplantation is the only curative option. However, its use is limited by donor availability, the risk of immune rejection, and high treatment costs. These challenges highlight the urgent need for safer, more effective therapies.

A new generation of gene editing technology

Gene editing technologies have opened new possibilities for curing monogenic diseases such as β-thalassemia. Unlike conventional CRISPR-Cas9 approaches, often described as “molecular scissors” that cut DNA, the transformer Base Editor (tBE) developed by the team acts more like a “gene correction pen.” It enables precise conversion of specific DNA bases without introducing double-strand breaks.

This approach avoids risks associated with DNA cutting, such as chromosomal deletions or rearrangements, and is expected to offer improved safety.

Rapid and durable clinical responses

The research team evaluated CS-101 in an investigator-initiated trial (IIT) (Figure 1) involving five patients with transfusion-dependent β-thalassemia. As of November 17, 2025, all patients achieved successful neutrophil and platelet engraftment following treatment.

Remarkably, patients became transfusion-independent within an average of just 16 days after a single dose. Hemoglobin levels rose to near-normal levels (12.4 g/dL) within three months and remained stable at approximately 13.4 g/dL after 15 months of follow-up. All patients have maintained transfusion independence for more than one year, with the longest follow-up exceeding 28 months.

Compared with existing CRISPR-based therapies, CS-101 demonstrated faster activation of fetal hemoglobin (HbF), more rapid hematopoietic recovery, and earlier restoration of normal hemoglobin levels. These advantages translate into shorter hospital stays and reduced healthcare burden. In addition, the therapy achieved higher HbF expression levels and showed no evidence of large genomic deletions, chromosomal abnormalities, or significant off-target effects, indicating a favorable safety profile.

Toward a first-in-class base editing therapy

To date, CS-101 has completed Phase I IND clinical studies and has been used to treat nearly 20 patients with β-thalassemia and sickle cell disease in China and internationally. All treated patients achieved transfusion independence, with sustained hemoglobin expression over time.

CS-101 has the potential to become the world’s first approved base editing therapeutic. With its strong efficacy, safety profile, and cost advantages, this innovative technology holds promise to benefit patients worldwide.

Source https://www.shanghaitech.edu.cn/eng/main.htm