AI Article Synopsis
- Cells previously thought to be uniform are actually made up of different subsets that have unique transcriptional states.
- The study introduces a new technique called SENT-seq, which allows researchers to investigate how effectively lipid nanoparticles (LNPs) deliver mRNA therapies by tracking various cellular responses on a single-cell level.
- Findings from SENT-seq reveal that certain cell subtypes show different levels of LNP uptake and are linked to specific genes, suggesting that these cellular differences could influence the effectiveness of mRNA therapies.
Article Abstract
Cells that were previously described as homogeneous are composed of subsets with distinct transcriptional states. However, it remains unclear whether this cell heterogeneity influences the efficiency with which lipid nanoparticles (LNPs) deliver messenger RNA therapies in vivo. To test the hypothesis that cell heterogeneity influences LNP-mediated mRNA delivery, we report here a new multiomic nanoparticle delivery system called single-cell nanoparticle targeting-sequencing (SENT-seq). SENT-seq quantifies how dozens of LNPs deliver DNA barcodes and mRNA into cells, the subsequent protein production and the transcriptome, with single-cell resolution. Using SENT-seq, we have identified cell subtypes that exhibit particularly high or low LNP uptake as well as genes associated with those subtypes. The data suggest that cell subsets have distinct responses to LNPs that may affect mRNA therapies.
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| http://dx.doi.org/10.1038/s41565-022-01146-9 | DOI Listing |
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