Histidinylated lPEI as new DNA carrier for in vitro and in vivo Gene Transfer with Low Toxicity

摘要

In this work, we focused on the design of lPEIderivatives bearing histidynyl moieties to increase thebuffering effect of lPEI in order to facilitate the cytosolicdelivery of polyplexes from endosomes. In vitroexperiments conducted on various cell lines demonstratedthat His-lPEI polyplexes with a histidine content of 25mol % complexed with pDNA encoding the luciferasegene gave the highest luciferase activity. The transfectionefficiency was at least as efficient as with pure lPEI anddepended on the cell type. More remarkable concerns thevery low level of toxicity of this new polymer comparedto lPEI. In vivo bioluminescence experiments conductedin mice with either systemic or intranasal injectiondemonstrated transfection efficiency in lung andconfirmed the absence of cytoxicity. Overall,histidinylated lPEI is a promising weakly toxic chemicalvectors for nucleic acids delivery.