Lipid nanoparticle-mediated mRNA delivery to CD34+ cells in rhesus monkeys

We report lipid nanoparticles that deliver mRNA to CD34+ cells in rhesus monkeys. Toevaluate how 105 LNPs delivered RNA in vivo, we used previously reported single cell multiomics-based screening system, Single cEll Nanoparticle Targeting-sequencing (SENT-seq). From single cell multiomics readout, we observed LNP barcodes and mRNA functional delivery in transcriptionally defined hematopoietic stem cell (HSC) populations, multipotent progenitors, and oligopotent progenitors suggesting that the LNPs delivered mRNA to HSCs in vivo. To complement these on-target data, we also sequenced LNP barcodes in liver cells, thereby quantifying delivery in a key off-target tissue. From evaluation of on- and off- target delivery ratio, LNP67 was indentified as a lead LNP. LNP67 delivers mRNA to murine HSCs in vivo, primary human HSCs ex vivo, and CD34+ cells in NHPs in vivo at 0.25 mg / kg doses. These data support the hypothesis that low dose delivery to hematopoietic stem and progenitor cells is feasible without targeting ligands.