Extended Data Fig. 1: High-throughput in vivo evaluation of a 98 LNP library using molecular barcoding in non-pregnant and pregnant mice.
From: Placenta-tropic VEGF mRNA lipid nanoparticles ameliorate murine pre-eclampsia
a, A large library of 98 LNP formulations was designed by synthesizing 24 unique ionizable lipid structures from 8 polyamine cores and 3 epoxide tails. 12 of these ionizable lipids were then further explored to formulate LNPs of varied excipient composition. b, Each of the 98 LNPs was formulated encapsulating a unique DNA barcode (b-DNA) to enable high-throughput, in vivo screening. The pooled LNPs were administered i.v. to non-pregnant and pregnant mice (n = 6 biological replicates) following which tissues were collected, processed, and prepared for next generation sequencing. Demultiplexing and subsequent data analysis identified a placenta-tropic LNP formulation. c, Heatmap depicting relative accumulation for each LNP/b-DNA in non-pregnant mouse tissues. Ion., ionizable; chol., cholesterol. Illustrations in b were created using BioRender (https://biorender.com).
