Figure 1.

Schematic displaying how Cas9 RNP/CPP complexes are hypothesized to be taken up and subsequentially escape from the endosomal pathway. First, the nanocomplex interacts with the cellular membrane of target cells (1) and is subsequently internalized (2) via endocytosis (3). Following acidification of the endosome, the amphipathic cell-penetrating peptides induce lytic membrane interactions with the endosomal membrane. Following endosomal membrane disruption, nanocomplexes are released into the cytosol (4). Nuclear localization signal (NLS) sequences on Cas9 allow internalization into the nucleus, where gene editing can occur (5). Created with BioRender.com, accessed on 24 December 2022.