{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE297nnn/GSE297473/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Homo sapiens"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE297473"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"In vivo genome editing of human hematopoietic stem cells for treatment of blood disorders using mRNA delivery","description":"Ex 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.","dates":{"publication":"2026/08/13"},"accession":"GSE297473","cross_references":{"GSM":["GSM8992770","GSM8992771","GSM8992772","GSM8992777","GSM8992778","GSM8992779","GSM8992773","GSM8992774","GSM8992775","GSM8992776","GSM8992759","GSM8992760","GSM8992761","GSM8992766","GSM8992767","GSM8992768","GSM8992769","GSM8992762","GSM8992763","GSM8992764","GSM8992765","GSM8992708","GSM8992709","GSM8992704","GSM8992705","GSM8992706","GSM8992707","GSM8992670","GSM8992671","GSM8992672","GSM8992673","GSM8992790","GSM8992678","GSM8992711","GSM8992679","GSM8992712","GSM8992713","GSM8992714","GSM8992674","GSM8992675","GSM8992676","GSM8992710","GSM8992677","GSM8992780","GSM8992781","GSM8992782","GSM8992783","GSM8992667","GSM8992788","GSM8992700","GSM8992701","GSM8992668","GSM8992789","GSM8992702","GSM8992669","GSM8992703","GSM8992784","GSM8992664","GSM8992785","GSM8992665","GSM8992786","GSM8992787","GSM8992666","GSM8992726","GSM8992727","GSM8992728","GSM8992729","GSM8992692","GSM8992693","GSM8992694","GSM8992695","GSM8992690","GSM8992691","GSM8992733","GSM8992734","GSM8992735","GSM8992736","GSM8992696","GSM8992730","GSM8992697","GSM8992698","GSM8992731","GSM8992699","GSM8992732","GSM8992719","GSM8992715","GSM8992716","GSM8992717","GSM8992718","GSM8992681","GSM8992682","GSM8992683","GSM8992684","GSM8992680","GSM8992722","GSM8992689","GSM8992723","GSM8992724","GSM8992725","GSM8992685","GSM8992686","GSM8992687","GSM8992720","GSM8992721","GSM8992688","GSM8992748","GSM8992749","GSM8992750","GSM8992755","GSM8992756","GSM8992757","GSM8992758","GSM8992751","GSM8992752","GSM8992753","GSM8992754","GSM8992737","GSM8992738","GSM8992739","GSM8992744","GSM8992745","GSM8992746","GSM8992747","GSM8992740","GSM8992741","GSM8992742","GSM8992743"],"GPL":["24676"],"GSE":["297473"],"taxon":["Homo sapiens"]}}