title: Linear polyethylenimine produced by partial acid hydrolysis of poly(2-ethyl-2-oxazoline) for DNA and siRNA delivery in vitro.
abstract: Polyethylenimines (PEIs) are the most efficient synthetic vectors for gene delivery available to date. With its high charge density and strong proton-buffering effect, PEI has an ability to condense DNA and small interfering RNA at physiologic pH. However, the polymer suffers from the disadvantage of high cellular toxicity. To reduce its cellular toxicity, we synthesized linear PEIs by partial hydrolysis of poly(2-ethyl-2-oxazoline). Three linear PEIs with different hydrolysis percentages (30%, 70%, and 96%, respectively) were produced as PEI30, PEI70, and PEI96. PEI30 and PEI96 cannot be considered as suitable transfection agents because of low transfection efficiency (PEI30) or high cellular toxicity (PEI96). PEI70 displayed very weak cell toxicity. The charge density of this polymer (PEI70) was strong enough to condense DNA and small interfering RNA at a physiologic pH of 7.4. Our results also show that PEI70 was highly efficient in DNA delivery and small interfering RNA-mediated knockdown of target genes. Thus, polymers such as PEI70 appear to be very promising vectors for gene delivery.
authors.affiliation: Orthopaedics Research Laboratory, Research Centre, Sacré-Coeur Hospital, Quebec, Canada.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Fernandes
authors.forename: Xingping
authors.initials: X
authors.lastname: Qiu
authors.forename: Françoise M
authors.initials: FM
authors.lastname: Winnik
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benderdour
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhang
authors.forename: Kerong
authors.initials: K
authors.lastname: Dai
authors.forename: Qin
authors.initials: Q
authors.lastname: Shi
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D010316:Particle Size; D011073:Polyamines / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D058105:Polymerization; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000493:pharmacokinetics*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D011073:Polyamines; D034741:RNA, Small Interfering; C511916:poly(2-ethyl-2-oxazoline); D011094:Polyethyleneimine; D004247:DNA; D001616:beta-Galactosidase
keywords: DNA; gene delivery; nonviral vector; polyethylenimine; small interfering RNA