Project description:We report the development of a new multiomic nanoparticle delivery system called Single cEll Nanoparticle Transcriptome-sequencing (SENT-seq), which quantifies how dozens of lipid nanoparticles (LNPs) deliver DNA barcodes and mRNA into cells, subsequent protein production, and the transcriptome, with single cell resolution. We show from the sequencing data that cell heterogeneity influences the efficiency with which LNPs deliver mRNA therapies, and identify cell subtypes that exhibit particularly high or low LNP uptake as well as genes associated with those subtypes. These data suggest that cell subsets have distinct responses to LNPs, and that these differential interactions can affect mRNA therapies.
Project description:Silencing HoxA1 in vivo by intraductal delivery of nanoparticle-formulated siRNA reduced mammary tumor incidence by 75% , reduced cell proliferation, and prevented loss of ER and PR expression. 8 week wild type FVB mouse whole mammary gland and 8week to 20 week transgenic FVB C3(1)-SV40Tag mouse whole mammary gland