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Meyer, Martin; Philipp, Alexander; Oskuee, Reza; Schmidt, Claudia; Wagner, Ernst (2008): Breathing Life into Polycations. Functionalization with pH-Responsive Endosomolytic Peptides and Polyethylene Glycol Enables siRNA Delivery. In: Journal of the American Chemical Society, Vol. 130, Nr. 11: S. 3272-3273
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Abstract

The lack of efficient delivery systems is still limiting the full therapeutic potential of siRNA. For the purpose of nucleic acid transfer, among other synthetic carrier systems, polycations have been applied. Favorable characteristics of suitable polymers include nucleic acid binding, compaction, protection, and biocompatibility. However the lack of nucleic acid transfer activity in transfection-based screening often abandons promising candidates. Here we present that functionalization may turn polycations with poor delivery activity into efficient carriers:  for example, polylysine, on its own lacking nucleic acid transfer activity, displayed high efficiency in siRNA delivery after modification with polyethylene glycol and a pH-responsive endosomolytic peptide. Hence these findings have implication for the selection process of polymeric carriers for siRNA.