The Transcriptional Response to Lung-Targeting Lipid Nanoparticles in Vivo .
Afsane RadmandMelissa P LokugamageHyejin KimCurtis DobrowolskiRyan ZenhausernDavid LoughreySebastian G HuayamaresMarine Z C HatitHuanzhen NiAda Del CidAlejandro J Da Silva SanchezKalina PaunovskaElisa Schrader EcheverriAram ShajiiHannah PeckPhilip J SantangeloJames E DahlmanPublished in: Nano letters (2023)
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 in vivo . Consistent with previous studies, we observed helper lipid-dependent tropism. After identifying and individually characterizing three LNPs that targeted different tissues, we studied the in vivo 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 in vivo .
Keyphrases
- single cell
- rna seq
- fatty acid
- gene expression
- binding protein
- regulatory t cells
- ejection fraction
- dendritic cells
- newly diagnosed
- stem cells
- high throughput
- amino acid
- electronic health record
- transcription factor
- machine learning
- cell therapy
- drug delivery
- patient reported outcomes
- mesenchymal stem cells
- deep learning