title: Recent developments in nucleic acid delivery with polyethylenimines.
abstract: Polyethylenimines (PEIs) have proven to be highly efficient and versatile agents for nucleic acid delivery in vitro and in vivo. Despite the low biodegradability of these polymers, they have been used in several clinical trials and the results suggest that the nucleic acid/PEI complexes have a good safety profile. The high transfection efficiency of PEIs probably relies on the fact that these polymers possess a stock of amines that can undergo protonation during the acidification of endosomes. This buffering capacity likely enhances endosomal escape of the polyplexes through the "proton sponge" effect. PEIs have also attracted great interest because the presence of many amino groups allow for easy chemical modifications or conjugation of targeting moieties and hydrophilic polymers. In the present chapter, we summarize and discuss the mechanism of PEI-mediated transfection, as well as the recent developments in PEI-mediated DNA, antisense oligonucleotide, and siRNA delivery.
authors.affiliation: Laboratoire "Vecteurs: Synthèse et Applications Thérapeutiques", UMR7199 CNRS-Université de Strasbourg, Faculté de Pharmacie, Illkirch, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Neuberg
authors.affiliation: Laboratoire "Vecteurs: Synthèse et Applications Thérapeutiques", UMR7199 CNRS-Université de Strasbourg, Faculté de Pharmacie, Illkirch, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Kichler
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D018014:Gene Transfer Techniques; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D009696:Nucleic Acids / Q000008:administration & dosage* / Q000737:chemistry; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry; D055672:Static Electricity; D014162:Transfection / Q000379:methods
chemical_list: D009696:Nucleic Acids; D034741:RNA, Small Interfering; D011094:Polyethyleneimine
keywords: Antisense oligonucleotides; Cationic polymers; Endosomal release; Gene therapy; Nonviral gene delivery; Polyethylenimines; Proton sponge effect; RNA interference and siRNA