Delivery of siRNA complementary to the fusion site of RUNX1::RUNX1T1 messenger RNA into primary human AML cells is improved nearly 10-fold with the use of targeted lipid nanoparticles. Transient silencing of RUNX1::RUNX1T1 disrupts leukemia stem cell renewal (black arrow) and is associated with increased expression of C/EBP and bidirectional myeloid differentiation into neutrophils or eosinophils (green arrow). Figure created with BioRender.com. Obeng E. (2025) https://BioRender.com/jfqkgjz.