Figure 1.
Design and optimization of polymeric carriers to enhance the immunostimulatory activity of 3pRNA RIG-I ligands. (a) Library of mPEG-block-[DMAEMA-co-AnMA[%]] polymers composed of 20–60% of alkyl methacrylate monomers (AnMA) containing n = 2–12 carbons was synthesized and screened to identify lead carriers for 3pRNA delivery. (b) Polymers are solubilized at low pH (pH 4) and mixed with 3pRNA to maximize electrostatic interactions followed by exchange into neutral pH buffer to form PEGylated nanoparticles loaded with 3pRNA. (c) Carriers capable of complexing 3pRNA and promoting endosomal escape increase 3pRNA delivery to cytosol, resulting in enhanced activation of RIG-I signaling. Image created with BioRender.com.