Fig. 6: Therapeutic vectors equipped with PVT1 enhancer achieve superior correction of the β-thalassemia phenotype compared to μLCR.

Mobilized peripheral blood CD34⁺ cells from 5 patients with beta-thalassemia major were transduced with the PVT1 and μLCR-shmiRNA vectors in the presence of cytokines and small molecules. The cells were cultured under erythroid conditions for 18 days, 2 days post transduction. a Absolute cell numbers (mean ± SEM; n = 5) during erythroid differentiation of transduced and untransduced cells. Bonferroni corrected Wilcoxon rank sum test p-values are shown. b HbF expression (as %HbF⁺ cells) measured by flow cytometry in enucleated and nucleated cells on day 18 of ex vivo erythroid differentiation. Tukey HSD post-hoc test adjusted p-values shown. c Globin chain production displayed as γ to β-like, γ to α, and β-like to α ratio in transduced and untransduced cells measured by HPLC. Tukey adjusted post-hoc test with Welch correction p-values shown. d HPLC trace profiles of globin chains in transduced and untransduced β0/β⁺ patient CD34⁺ derived erythroid cells. e Percentage of enucleated cells on day 18 of the differentiation measured by flow cytometry. Bonferroni corrected Welch t-test p-values are shown. f Flow cytometry measured intensity of reactive oxygen species (ROS) post CFSE staining of erythroid cells on day 11 of the erythroid culture. Post-hoc Tukey HSD test adjusted p-values shown. g Characteristic morphology of transduced and untransduced erythroid cells in different erythroid differentiation and maturation stages. Non-significant (ns) ≥0.1. Boxplots extend to IQR (25^th and 75^th percentile). Median is shown as a thick horizontal line and whiskers extend to 1.5x IQR. Untr.: Untransduced control. Source data for all relevant panels are provided within the Source Data file.