Abstract
We present a postfunctionalization strategy to formulate noncationic RNA–polymer complexes for RNA delivery. Utilizing the methylated pyridinium moieties on the polymer, RNA–polymer polyelectrolytes were first formed via electrostatic interaction. Next, the polyelectrolytes were partially cross-linked with dithiothreitol, “locking” the RNA inside the complex and leaving the rest of the N-methylated pyridyl disulfide groups to subsequently react with thiols. We carried out the postfunctionalization using thiolated oligoethylene glycol and removed a majority of the cationic moieties among the RNA–polymer complexes. The strategy facilitates the noncationic RNA–polymer complexes with tunable RNA release rates in the presence of intracellularly abundant glutathione. With significantly reduced cytotoxicity, the resultant complexes protect RNA against the enzymatic degradation by ribonuclease A and fetal bovine serum. Moreover, the RNA–polymer complexes demonstrated successful siRNA delivery and gene specific kn...
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