The Transcriptional Response to Lung-Targeting Lipid Nanoparticles <i>in Vivo</i>.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36701517.
- Also identified by DOI 10.1021/acs.nanolett.2c04479 and PMC identifier 9912332.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Lipid nanoparticles (LNPs) have delivered RNA to hepatocytes in patients, underscoring the potential impact of nonliver delivery. Scientists can shift LNP tropism to the lung by adding cationic helper lipids; however, the biological response to these LNPs remains understudied. To evaluate the hypothesis that charged LNPs lead to differential cellular responses, we quantified how 137 LNPs delivered mRNA to 19 cell types <i>in vivo</i>. Consistent with previous studies, we observed helper lipid-dependent tropism. After identifying and individually characterizing three LNPs that targeted different tissues, we studied the <i>in vivo</i> transcriptomic response to these using single-cell RNA sequencing. Out of 835 potential pathways, 27 were upregulated in the lung, and of these 27, 19 were related to either RNA or protein metabolism. These data suggest that endogenous cellular RNA and protein machinery affects mRNA delivery to the lung <i>in vivo</i>.
Medical subject headings
- Lipids
- Nanoparticles