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. 2023 Sep 20;14:5850. doi: 10.1038/s41467-023-40923-5

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Panel a shows the proportion of RBCs containing a minimum of 10 pg of HbF per cell measured by flow cytometry in BCL^shmiR after drug product infusion. Dotted green lines represent Transfused BCL^shmiR (patients 3 and 10) while green solid lines represent the Untransfused BCL^shmiR patients at baseline (when available) and after drug product infusion. The vertical dashed gray line indicates 4.5 months after drug product infusion, which corresponds to timepoints for which previously transfused RBCs were no longer detectable (HbA = 0%) in Untransfused BCL^shmiR. For dotted green lines later than 4.5 months we show the percentage of RBCs containing a minimum of 10 pg of HbF among Untransfused RBCs. For timepoints earlier than ~4.5 months the percentage of RBCs containing a minimum of 10 pg of HbF reflects the presence of transfused RBCs. The black solid line shows a fitting for the Untransfused BCL^shmiR obtained by a linear mixed-effects model, and the gray region indicates the 95% confidence interval for this linear mixed-effects model (see below). Panel b shows the difference in the proportion of RBCs containing a minimum of 10 pg of HbF between Untransfused BCL^shmiR (n = 7) in green, HU High Responders (n = 10), and HU Low Responders (n = 8) in purple (median–IQR). Panel c shows the proportion of RBC containing more than 70% of HbS as a percentage of total Hb, as determined by flow cytometry based on HbF quantification (excluding HbA2), in Untransfused BCL^shmiR after drug product infusion, for HU High Responders in blue, and HU Low Responders in purple. A linear mixed-effects model (described in the “Methods” subsection“Data analysis, statistics, and reproducibility”) was used to estimate the mean kinetics of HbF induction as a function of time for the seven non-transfused subjects. Boxplot properties and the method used to compute the p-values in this study are described in the “Methods” subsection “Data analysis, statistics, and reproducibility”. Source data are provided as a Source Data file.