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This content will become publicly available on March 12, 2025

Title: Cationic cholesterol-dependent LNP delivery to lung stem cells, the liver, and heart

Adding a cationic helper lipid to a lipid nanoparticle (LNP) can increase lung delivery and decrease liver delivery. However, it remains unclear whether charge-dependent tropism is universal or, alternatively, whether it depends on the component that is charged. Here, we report evidence that cationic cholesterol-dependent tropism can differ from cationic helper lipid-dependent tropism. By testing how 196 LNPs delivered mRNA to 22 cell types, we found that charged cholesterols led to a different lung:liver delivery ratio than charged helper lipids. We also found that combining cationic cholesterol with a cationic helper lipid led to mRNA delivery in the heart as well as several lung cell types, including stem cell-like populations. These data highlight the utility of exploring charge-dependent LNP tropism.

 
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Award ID(s):
2145235
PAR ID:
10494468
Author(s) / Creator(s):
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Publisher / Repository:
PNAS
Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Volume:
121
Issue:
11
ISSN:
0027-8424
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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