Simple Modifications of Branched PEI Lead to Highly Efficient siRNA Carriers with Low Toxicity

• DOI: 10.1021/bc800065f
• Publication Date: 2008-06-14T07:02:04Z
• Authors: Arkadi Zintchenko; Alexander Philipp; Ali Dehshahri; Ernst Wagner
• Keywords: Ethyl acrylate

Polymer carriers like PEI which proved their efficiency in DNA delivery were found to be far less effective for the applications with siRNA. In current study, we generated a number of nontoxic derivates branched through modification amines by ethyl acrylate, acetylation primary amines, or introduction negatively charged propionic acid succinic groups polymer structure. The resulting products showed high siRNA-mediated knockdown target gene. particular, succinylation resulted up 10-fold lower toxicity comparison unmodified PEI. Formulations siRNA succinylated able induce remarkable (80% relative untreated cells) luciferase gene at lowest tested concentration 50 nM Neuro2ALuc cells. polyplex stability assay revealed that formulations are stable physiological saline is independent affinity chain. improved properties modified as carrier largely consequence toxicity. order achieve significant gene, PEI-based has applied higher concentrations, required most probably sufficient accumulation and proton sponge effects endosomes. Unmodified highly toxic such concentrations. contrast, analogues can concentrations genes without side effects.