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Creators/Authors contains: "Huayamares, Sebastian G"

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  1. ; ; ; ; ; ; ; ; ; ; et al (, Nature Biotechnology)
    Free, publicly-accessible full text available November 22, 2025
  2. ; ; ; ; ; ; ; ; ; ; et al (, Proceedings of the National Academy of Sciences)
    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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