Unlocking the endosome allows the release of siRNAs into the cytoplasm following the cellular uptake of nanoparticles made up of siRNAs and polyspermine imidazole-4,5-imine. In their Communication on page 7938 ff., T. Jin and co-workers show that a polymer of spermine with a pH-sensitive linkage degrades, upon entry into the endosome, into spermine and a nontoxic metabolite. Assays in cells and mice showed effective gene silencing by the polymer-packaged siRNAs without cytotoxicity.
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