Skip to main content
. 2024 Oct 24;18(44):30293–30306. doi: 10.1021/acsnano.4c05169

Figure 1.

Figure 1

In utero delivery of densely PEGylated LNPs globally transfects the brain in utero with mRNA for gene editing enzymes. In this report, we demonstrate that ADP-LNPs can safely and efficiently transfect large volumes of the fetal brain tissue with mRNA after an in utero ICV injection and have the transfection efficiency needed for treating genetic CNS disorders. We show here that an in utero ICV injection of ADP-LNPs can transfect and edit 30% of the entire fetal mouse brain cells with Cre mRNA, including the proliferating NSPCs, which populate the entire adult mouse brain as the mouse develops into adulthood. In addition, in utero ICV injection of ADP-LNPs transfected and edited 15% of the entire fetal mouse brain cells with Cas9 mRNA and efficiently edited NSPCs. These experiments demonstrate mRNA-based nonviral gene editing in NSPCs in utero using Cas9 mRNA, achieving high efficiency and minimal toxicity.