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You have full access to this article via your institution. Download PDF Beam Therapeutics’ early clinical data on its base-editing therapy BEAM-101 shows for the first time that the
technology restores functional hemoglobin in people with sickle cell disease. In four patients treated with BEAM-101, functional fetal hemoglobin levels increased to over 60% at 1–6 months
follow-up, and patients’ red blood cells had less sickling, reduced cell adhesion and improved flow properties. Moreover, no patients had the painful vaso-occlusive crises typical of sickle
cell disease. Beam will release further data at December’s American Society for Hematology meeting. BEAM-101 uses adenine base editors to introduce single-base changes in the promoter
regions of the γ-globin genes _HBG1_ and _HBG2_ in patients’ stem cells ex vivo. These changes disrupt the binding of the BCL11A repressor, increasing the expression of fetal hemoglobin. If
approved, BEAM-101 would sit alongside Vertex’s CRISPR-based therapy Casgevy (exagamglogene autotemcel) and bluebird bio’s gene therapy Lyfgenia (lovotibeglogene autotemcel). In separate
trials, those sickle cell therapies increased functional hemoglobin to around 40% at two years. Although BEAM-101 was not linked to serious adverse effects, one person died in the ongoing
trial, likely as a result of the toxicity of the drug used to deplete the patient’s existing stem cells. Beam has an alternative depletor, an antibody targeting CD117, in preclinical
testing. In this approach, stem cells are base edited to alter not only _HBG1_ and _HBG2_ but also _CD117_ so they cannot bind the depleting antibody. BEAM-101 is one of at least ten
base-editing-based therapies in clinical trials. Another is BEAM-201, an allogeneic CAR-T cell therapy with base edits to four genes, which abolished tumors in two of three treated patients
with blood cancers. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Base editing boosts hemoglobin in sickle cell disease. _Nat Biotechnol_ 42, 1759
(2024). https://doi.org/10.1038/s41587-024-02517-4 Download citation * Published: 11 December 2024 * Issue Date: December 2024 * DOI: https://doi.org/10.1038/s41587-024-02517-4 SHARE THIS
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