Helper lipid charge influences
LNP in vivo tropism
at the cellular level. (a) LNPs were formulated to carry a DNA barcode
and Cre mRNA; 137 LNPs were pooled into their respective libraries
and were then administered to Ai14 mice. After 4 days, tdTomato signal
was quantified and tdTomato+ cells were isolated. Next-generation
sequencing identified LNPs that functionally transfected cells in vivo. (b) Normalized delivery of all LNPs across all
cell types in each library. The control, unencapsulated barcode, delivered
less efficiently than barcodes delivered by LNPs. tdTomato+ signal in (c) lung, (d) liver, (e) spleen, (f) heart, and (g) kidney
cells. These data suggest preferential delivery to lung cell types
by the cationic LNPs; no delivery was observed by the neutral and
anionic LNP pools to lung cell types. ****P <
0.0001, ***P < 0.0006, **P <
0.01, *P < 0.03, one-way ANOVA, average ±
SEM. (h) Normalized delivery as a function of hydrodynamic diameter.