Other
22 Authors
- John S,
- Johnson LT,
- Moore S,
- Weiss MJ,
- Xiao Y,
- Liu DR,
- Smith C,
- Levine RM,
- Mayberry K,
- Yen JS,
- Bian X,
- Sun Y,
- Sung YC,
- Chatterjee S,
- Siegwart DJ,
- Wang X,
- Dilliard SA,
- Yamada K,
- Zhang CC,
- Lian X,
- Liu X,
- Newby GA
| First Author | Lian X | Year | 2024 |
| Journal | Nat Nanotechnol | Volume | 19 |
| Issue | 9 | Pages | 1409-1417 |
| PubMed ID | 38783058 | Mgi Jnum | J:354940 |
| Mgi Id | MGI:7736827 | Doi | 10.1038/s41565-024-01680-8 |
| Citation | Lian X, et al. (2024) Bone-marrow-homing lipid nanoparticles for genome editing in diseased and malignant haematopoietic stem cells. Nat Nanotechnol 19(9):1409-1417 |
| abstractText | 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. |
