βT87Q-Globin Gene Therapy Reduces Sickle Hemoglobin Production, Allowing for Ex Vivo Anti-sickling Activity in Human Erythroid Cells.

ABSTRACT: Lentiviral addition of βT87Q-globin, a modified β-globin with an anti-sickling mutation, is currently being used in gene therapy trials for sickle cell disease (SCD) and β-thalassemia patients. βT87Q-globin interferes with sickle hemoglobin (HbS) polymerization. Here, we generated the SCD mutation in an immortalized human erythroid cell line (HUDEP-2) to investigate the anti-sickling activity of βT87Q-globin. Sickle HUDEP-2 (sHUDEP-2) cells produced robust HbS after differentiation and sickled under deoxygenated conditions, comparable with SCD CD34⁺ progeny. Lentiviral transduction provided 9.5-26.8 pg/cell βT87Q-globin (R² = 0.83) in a vector copy number (VCN)-dependent manner, resulting in a significant reduction of sickling ratios (R² = 0.92). Interestin

SUBMITTER: Demirci S 

PROVIDER: S-EPMC7210457 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature