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Nanoparticle-encapsulated siRNAs for gene silencing in the haematopoietic stem-cell niche
Name
nihms-1626519.pdf
Description
Accepted version
Size
3.19 MB
Format
Adobe PDF
Checksum (MD5)
10d9362b6472d7a5a1c27051d83f9099
Author(s)
Krohn-Grimberghe, Marvin
Mitchell, Michael J
Schloss, Maximilian J
Khan, Omar F
Courties, Gabriel
Guimaraes, Pedro PG
Rohde, David
Cremer, Sebastian
Kowalski, Piotr S
Sun, Yuan
Date Issued
2020
Journal
Nature Biomedical Engineering
Publisher
Springer Science and Business Media LLC
Version
Author's final manuscript
Abstract
© 2020, The Author(s), under exclusive licence to Springer Nature Limited. Bone-marrow endothelial cells in the haematopoietic stem-cell niche form a network of blood vessels that regulates blood-cell traffic as well as the maintenance and function of haematopoietic stem and progenitor cells. Here, we report the design and in vivo performance of systemically injected lipid–polymer nanoparticles encapsulating small interfering RNA (siRNA), for the silencing of genes in bone-marrow endothelial cells. In mice, nanoparticles encapsulating siRNA sequences targeting the proteins stromal-derived factor 1 (Sdf1) or monocyte chemotactic protein 1 (Mcp1) enhanced (when silencing Sdf1) or inhibited (when silencing Mcp1) the release of stem and progenitor cells and of leukocytes from the bone marrow. In a mouse model of myocardial infarction, nanoparticle-mediated inhibition of cell release from the haematopoietic niche via Mcp1 silencing reduced leukocytes in the diseased heart, improved healing after infarction and attenuated heart failure. Nanoparticle-mediated RNA interference in the haematopoietic niche could be used to investigate haematopoietic processes for therapeutic applications in cancer, infection and cardiovascular disease.
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
10.1038/S41551-020-00623-7
