Fig. 1

The principle and applications of modified mRNA. Modified mRNA can be transfected via several routes to the target cell, e.g., intraperitoneally, intravenously, or intratracheally. After endocytosis, the incorporation of naturally occurring, noncanonical nucleosides (indicated as red dots) into in vitro transcribed mRNA prevents activation of and consequently degradation by endosomal (Toll-like receptors, TLRs) and cytoplasmatic (MDA5, RIG1) mRNA-Sensors, thus being efficiently translated into a functional protein at the cell’s ribosomes. Different target applications can be applied for modified mRNA: (a) genome targeting, resulting in functional nucleases (e.g., zink-finger nucleases, CRISPR/Cas9) that bind and create sequence-specific double-strand breaks within the genome to facilitate gene correction, gene replacement or gene knock-out; (b) protein supplementation, where endogeneous protein malfunction can be overcome by restoring normal protein function; (c) extrinsic/receptor function in case of improper cell signaling