Fig. 1

Barriers to RNA delivery. Left: RNA in circulation is vulnerable to RNase degradation and phagocytosis, and access to targeted tissue is blocked by physical barriers (e.g. endothelial and epithelial layers) and renal and hepatic clearance. Right: Cytoplasmic delivery is impaired by the plasma membrane, degradation within lysosomes, and nonspecific dsRNA immune activation. The latter can occur within the endosome by activating a Toll-like receptor (TLR) or in the cytoplasm by activating RIG1 or Protein kinase R (PKR). Images courtesy of Louisa Howard at Dartmouth University