Cationic cholesterol-dependent LNP delivery to lung stem cells, the liver, and heart.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38437539.
- Also identified by DOI 10.1073/pnas.2307801120 and PMC identifier 10945827.
- Licence recorded as CC BY-NC-ND.
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Abstract
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.
Medical subject headings
- Liver
- Stem Cells