GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE297nnn/GSE297473/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE297473GEOGSEfalseIn vivo genome editing of human hematopoietic stem cells for treatment of blood disorders using mRNA deliveryEx vivo autologous hematopoietic stem cell (HSC) gene therapy provides a promising treatment option for hematological disorders. However, current methods involve complex processes and chemotherapeutic conditioning, leading to limited accessibility for treatment and significant side effects. Here, we develop antibody-free targeted lipid nanoparticles (LNPs) for mRNA delivery to HSCs in vivo, enabling efficient base editing of the γ-globin gene (HBG1/2) promoters target in human HSCs to reactivate fetal hemoglobin in derived erythroid cells. Delivery of ABE8e/sgRNA mRNA with optimized LNPs achieves efficient in vivo base editing of HBG1/2 in transfusion-dependent β-thalassemia (TDT) patients-derived HSCs engrafted in immunodeficient NCG-X mice, showing restored globin chain balance in erythroid cells. Our research indicates that using LNPs for genome editor delivery achieves efficient editing of endogenous genes of human HSCs. This non-viral delivery system eliminates the need for harvesting or mobilizing HSCs, providing a potent and one-time treatment potential for blood disorders like sickle cell disease (SCD) and TDT.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 sapiens