Two gene therapy products have been approved by the US Food and Drug Administration for sickle cell disease. Nearly all patients in the clinical trials that led to approval either were sickle hemoglobin (HbS) gene homozygotes (sickle cell anemia) or had HbS-β0 thalassemia. HbSC disease, caused by compound heterozygosity for HbS and hemoglobin C genes, is the second most common genotype of sickle cell disease. Gene therapy has not been tested in patients with HbSC disease who are severely symptomatic. We discuss the pathophysiology and clinical features of HbSC disease and how gene therapy is likely to provide a curative option for some individuals. We also discuss the mechanism through which fetal hemoglobin (HbF) and HbF-like HbA (HbAT87Q) might mitigate adverse clinical outcomes and end-organ damage in patients with HbSC disease and other compound heterozygous sickle hemoglobinopathies.
Skip Nav Destination
PERSPECTIVE|
November 13, 2025
Gene therapy for HbSC disease and other compound heterozygous sickle hemoglobinopathies: a time for inclusion Available to Purchase
Andrew Wilks,
Andrew Wilks
1Division of Hematology and Medical Oncology, Department of Medicine, Center of Excellence for Sickle Cell Disease, Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, MA
Search for other works by this author on:
Martin H. Steinberg,
Martin H. Steinberg
1Division of Hematology and Medical Oncology, Department of Medicine, Center of Excellence for Sickle Cell Disease, Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, MA
Search for other works by this author on:
Haydar Frangoul
Haydar Frangoul
2Sarah Cannon Cancer Insitute, Pediatric Hematology/Oncology and Cellular Therapy, TriStar Centennial Medical Center, Nashville, TN
Search for other works by this author on:
Blood (2025) 146 (20): 2385–2391.
Article history
Submitted:
May 13, 2025
Accepted:
July 31, 2025
First Edition:
August 20, 2025
Citation
Andrew Wilks, Martin H. Steinberg, Haydar Frangoul; Gene therapy for HbSC disease and other compound heterozygous sickle hemoglobinopathies: a time for inclusion. Blood 2025; 146 (20): 2385–2391. doi: https://doi.org/10.1182/blood.2025029964
Download citation file:
My Account
Sign In
November 13 2025
Advertisement intended for health care professionals
Cited By
Advertisement intended for health care professionals
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal