| Literature DB >> 33737751 |
M Kyle Cromer1, Joab Camarena1, Renata M Martin1, Benjamin J Lesch1, Christopher A Vakulskas2, Nicole M Bode2, Gavin Kurgan2, Michael A Collingwood2, Garrett R Rettig2, Mark A Behlke2, Viktor T Lemgart1, Yankai Zhang3, Ankush Goyal3, Feifei Zhao4,5, Ezequiel Ponce1, Waracharee Srifa1, Rasmus O Bak6,7, Naoya Uchida8, Ravindra Majeti4,5, Vivien A Sheehan3, John F Tisdale8, Daniel P Dever9, Matthew H Porteus10,11.
Abstract
β-Thalassemia pathology is due not only to loss of β-globin (HBB), but also to erythrotoxic accumulation and aggregation of the β-globin-binding partner, α-globin (HBA1/2). Here we describe a Cas9/AAV6-mediated genome editing strategy that can replace the entire HBA1 gene with a full-length HBB transgene in β-thalassemia-derived hematopoietic stem and progenitor cells (HSPCs), which is sufficient to normalize β-globin:α-globin messenger RNA and protein ratios and restore functional adult hemoglobin tetramers in patient-derived red blood cells. Edited HSPCs were capable of long-term and bilineage hematopoietic reconstitution in mice, establishing proof of concept for replacement of HBA1 with HBB as a novel therapeutic strategy for curing β-thalassemia.Entities:
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Year: 2021 PMID： 33737751 PMCID： PMC8265212 DOI： 10.1038/s41591-021-01284-y
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440