Gene-editing therapy hits 100% remission across 30-plus sickle cell and thalassemia patients

A base-editing therapy developed by Shanghai-based CorrectSequence Therapeutics has achieved transfusion independence or freedom from painful vaso-occlusive crises in every patient treated to date — more than 30 across four continents — according to clinical data published September 7 in the journal Cell Stem Cell.prnewswire+1

The study extends earlier findings, published in Nature in April, that showed all five Chinese patients with transfusion-dependent beta-thalassemia became transfusion-free after a single infusion of CS-101, the company's lead therapy. The new paper adds four patients from Nigeria, Laos, Malaysia, and Pakistan — one with sickle cell disease and three with beta-thalassemia — demonstrating that the approach works across diverse genetic backgrounds and mutation types.pharmaphorum+2

How tBE Differs from CRISPR

The therapies rely on CorrectSequence's proprietary transformer Base Editor, or tBE, which converts individual DNA bases without cutting both strands of the double helix. Conventional CRISPR-Cas9 and Cas12a nucleases create double-strand breaks that can trigger chromosomal rearrangements, large deletions, and activation of the tumor-suppressor gene p53. The tBE system uses a dual guide-RNA "lock-and-key" mechanism that activates editing only at the intended target site, and the company reported no detectable off-target mutations across all treated patients.ashpublications+1

In sickle cell disease trials, the company said tBE achieved neutrophil engraftment in 13 days compared with 27 days for Cas9 and 23 days for Cas12a, while sustaining fetal hemoglobin above 60 percent of total hemoglobin — outperforming nuclease-based regimens, which remained below 50 percent.prnewswire

Clinical Results Across Populations

The Nigerian sickle cell patient, a 21-year-old woman who had experienced more than four vaso-occlusive crises in the year before treatment, saw her total hemoglobin rise from 7.7 to 12.9 grams per deciliter within three months. At 15.5 months of follow-up, she had experienced no further crises. The three beta-thalassemia patients, ages 3 to 29, all achieved sustained transfusion independence at a median follow-up of 17.5 months.trial.medpath+1

What Comes Next

CS-101, which CorrectSequence describes as the first base-editing therapy to enter clinical development — with the first patient dosed in October 2023 — has completed Phase I and is now in pivotal trials. The company is also expanding its tBE platform into metabolic and cardiovascular diseases, including familial chylomicronemia syndrome and atherosclerotic cardiovascular disease.pharmaphorum+1

"This Cell Stem Cell paper validates tBE's broad applicability across diverse genetic backgrounds, completing the translational journey from bench to global clinical application," said Professor Chen Jia, founder of CorrectSequence and director of the Gene Editing Center at ShanghaiTech University.prnewswire