Abstract
Viruses protect their genome and after endosome escape can disassemble to release their genetic contents. These two functions of protection and triggered-release are competing functionalities that have been difficult to engineer into nonviral transfection reagents. In order to mimic viral condensation of DNA, packaging and protection, and triggered release, we have designed a novel photolabile monomer, P25M, for plasmid DNA (pDNA) delivery. P25M was synthesized via a 6-step reaction scheme and consists of three functional domains: 1) a cationic domain of 25 kDa polyethylenimine (PEI) to electrostatically condense the pDNA; 2) a polymerizable domain (a methacrylamide moiety) for crosslinking the pDNA within the polyplex; and 3) a photolabile nitrobenzyl domain for triggered release by 365 nm light (Fig.
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