Biomarker implications of gene editing in hematologic diseases: latest updates from ASH 2025
TL;DR
Overall, ASH 2025 suggests a shift from achieving gene editing to quantifying efficacy, durability, and safety, with standardized biomarker frameworks likely to play an increasingly important role in future clinical translation.
Abstract
The 2025 American Society of Hematology (ASH) Annual Meeting highlighted rapid advances in gene editing for hematologic diseases, with increasing emphasis on precision editing and early exploration of in vivo delivery strategies. Beyond technological development, several measurable parameters are emerging as potential biomarkers, including fetal hemoglobin (HbF), F-cell proportion, HbF/F-cell, editing durability, and long-term clonal monitoring. Clinical studies demonstrated that disruption of the BCL11A enhancer or editing of the HBG1/2 promoter can induce sustained HbF reactivation, which is associated with reduced transfusion burden or transfusion independence in transfusion-dependent β-thalassemia and improved clinical outcomes in sickle cell disease. Near-pancellular HbF distribution and HbF/F-cell levels above anti-sickling thresholds further support the pharmacodynamic value of HbF-related biomarkers. Long-term follow-up studies have also incorporated editing durability and clonal monitoring into safety assessment frameworks. Emerging platforms such as RNA Gene Writer and CD90-targeted virus-like particles have demonstrated the feasibility of in vivo hematopoietic stem cell editing, although challenges related to targeting efficiency, delivery specificity, immunogenicity, and long-term safety remain. Overall, ASH 2025 suggests a shift from achieving gene editing to quantifying efficacy, durability, and safety, with standardized biomarker frameworks likely to play an increasingly important role in future clinical translation.