International Journal of Medical Advances and Discoveries

International Journal of Medical Advances and Discoveries | Vol. 17, No. 8, August 2026 | pp. 73–79

DOI: 10.46882/2026/IJMAD/170873

Original Research Article

Title: Clinical Efficacy of CRISPR-Cas12b Base Editing for Severe Beta-Thalassemia: A Phase II Trial

Names of Authors: Amina O. Bello¹, Chinedu K. Okafor²

Authors’ Affiliations: ¹Department of Hematology, College of Medicine, University of Ibadan, Ibadan, Nigeria; ²Center for Human Genetics, University of Nigeria Teaching Hospital, Enugu, Nigeria

Abstract: Base editing offers a highly precise alternative to double-stranded DNA cleavage technologies, minimizing the risks of unwanted chromosomal translocations in therapeutic genome modification. This Phase II open-label clinical trial evaluated the safety, efficacy, and hematological impacts of an autologous CD34+ hematopoietic stem cell therapy modified via a novel CRISPR-Cas12b adenine base editor (ABE-9x) designed to disrupt the BCL11A erythroid enhancer. A cohort of 28 patients aged 12 to 35 with transfusion-dependent beta-thalassemia was enrolled. Following myeloablative busulfan conditioning, engineered cells were re-infused, and patients were tracked for a median of 18 months. The primary endpoint was transfusion independence at month 12. At the 12-month milestone, 92.8% (26/28) of participants achieved complete transfusion independence. Mean total hemoglobin concentrations rose from a baseline of 6.4 ± 0.8 g/dL to 12.1 ± 1.3 g/dL at 12 months post-infusion (p < 0.001). This hematological correction was driven by a robust reactivation of fetal hemoglobin (HbF), which constituted 46.2% ± 5.4% of total hemoglobin. Next-generation deep sequencing confirmed a mean base-editing efficiency of 84.3% in bone marrow aspirates, with zero detectable off-target edits across 150 pre-selected candidate genomic loci. The safety profile matched typical autologous transplantation outcomes, with no occurrences of secondary malignancies or clonal hematopoiesis. These findings demonstrate that CRISPR-Cas12b base editing of the BCL11A enhancer is highly effective and exhibits an excellent safety profile, presenting a durable, curative option for severe beta-thalassemia.

Keywords: CRISPR-Cas12b, Base editing, Beta-thalassemia, Fetal hemoglobin, BCL11A enhancer, Transfusion independence, Hematopoietic stem cells

Manuscript Timeline: Received: April 11, 2026; Revised: May 29, 2026; Accepted: June 18, 2026; Published: August 04, 2026

Citation: Bello, A. O., & Okafor, C. K. (2026). Clinical Efficacy of CRISPR-Cas12b Base Editing for Severe Beta-Thalassemia: A Phase II Trial. International Journal of Medical Advances and Discoveries, 17(8), 73–79. doi:10.46882/2026/IJMAD/170873

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