학술논문
Bone-marrow-homing lipid nanoparticles for genome editing in diseased and malignant haematopoietic stem cells
Document Type
Article
Author
Lian, Xizhen; Chatterjee, Sumanta; Sun, Yehui; Dilliard, Sean A.; Moore, Stephen; Xiao, Yufen; Bian, Xiaoyan; Yamada, Kohki; Sung, Yun-Chieh; Levine, Rachel M.; Mayberry, Kalin; John, Samuel; Liu, Xiaoye; Smith, Caroline; Johnson, Lindsay T.; Wang, Xu; Zhang, Cheng Cheng; Liu, David R.; Newby, Gregory A.; Weiss, Mitchell J.; Yen, Jonathan S.; Siegwart, Daniel J.
Source
Nature Nanotechnology; September 2024, Vol. 19 Issue: 9 p1409-1417, 9p
Subject
Language
ISSN
17483387; 17483395
Abstract
Therapeutic genome editing of haematopoietic stem cells (HSCs) would provide long-lasting treatments for multiple diseases. However, the in vivo delivery of genetic medicines to HSCs remains challenging, especially in diseased and malignant settings. Here we report on a series of bone-marrow-homing lipid nanoparticles that deliver mRNA to a broad group of at least 14 unique cell types in the bone marrow, including healthy and diseased HSCs, leukaemic stem cells, B cells, T cells, macrophages and leukaemia cells. CRISPR/Cas and base editing is achieved in a mouse model expressing human sickle cell disease phenotypes for potential foetal haemoglobin reactivation and conversion from sickle to non-sickle alleles. Bone-marrow-homing lipid nanoparticles were also able to achieve Cre-recombinase-mediated genetic deletion in bone-marrow-engrafted leukaemic stem cells and leukaemia cells. We show evidence that diverse cell types in the bone marrow niche can be edited using bone-marrow-homing lipid nanoparticles.