G2B: an optimized lentiviral vector with enhanced titer and β-globin expression for improved β-thalassemia gene therapy.

ABSTRACT: Gene therapy using lentiviral vectors offers a promising alternative treatment for β-thalassemia, a common monogenic blood disorder. Although the BB305 vector has demonstrated long-term clinical success-enabling most β-thalassemia patients to become transfusion-independent and substantially reducing vaso-occlusive events in sickle cell disease-there remains a significant opportunity to enhance its efficacy and lower production costs. Here, we present G2B, a novel hemoglobin beta gene (HBB) lentiviral vector derived from BB305-like constructs (BB305L), engineered by shortening the locus control region (LCR) and incorporating a mutated HBG2 promoter. Compared to BB305L, G2B achieves a ~4-fold increase in lentiviral titer and a 60% boost in β-globin expression. In a transplantation model usin

SUBMITTER: Gao ZY 

PROVIDER: S-EPMC12530315 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature