RRC ID 65443
著者 Nicolle L, Casper J, Willimann M, Journot CMA, Detampel P, Einfalt T, Grisch-Chan HM, Thöny B, Gerber-Lemaire S, Huwyler J.
タイトル Development of Covalent Chitosan-Polyethylenimine Derivatives as Gene Delivery Vehicle: Synthesis, Characterization, and Evaluation.
ジャーナル Int J Mol Sci
Abstract There is an increasing interest in cationic polymers as important constituents of non-viral gene delivery vectors. In the present study, we developed a versatile synthetic route for the production of covalent polymeric conjugates consisting of water-soluble depolymerized chitosan (dCS; MW 6-9 kDa) and low molecular weight polyethylenimine (PEI; 2.5 kDa linear, 1.8 kDa branched). dCS-PEI derivatives were evaluated based on their physicochemical properties, including purity, covalent bonding, solubility in aqueous media, ability for DNA condensation, and colloidal stability of the resulting polyplexes. They were complexed with non-integrating DNA vectors coding for reporter genes by simple admixing and assessed in vitro using liver-derived HuH-7 cells for their transfection efficiency and cytotoxicity. Using a rational screening cascade, a lead compound was selected (dCS-Suc-LPEI-14) displaying the best balance of biocompatibility, cytotoxicity, and transfection efficiency. Scale-up and in vivo evaluation in wild-type mice allowed for a direct comparison with a commercially available non-viral delivery vector (in vivo-jetPEI). Hepatic expression of the reporter gene luciferase resulted in liver-specific bioluminescence, upon intrabiliary infusion of the chitosan-based polyplexes, which exceeded the signal of the in vivo jetPEI reference formulation by a factor of 10. We conclude that the novel chitosan-derivative dCS-Suc-LPEI-14 shows promise and potential as an efficient polymeric conjugate for non-viral in vivo gene therapy.
巻・号 22(8)
公開日 2021-4-7
DOI 10.3390/ijms22083828
PII ijms22083828
PMID 33917124
PMC PMC8067803
MeSH Animals Cell Line, Tumor Cell Survival Chemical Phenomena Chemistry Techniques, Synthetic Chitosan / chemistry* Colloids / chemistry DNA / chemistry Gene Expression Gene Transfer Techniques* Genes, Reporter Genetic Vectors Humans Magnetic Resonance Spectroscopy Mice Polyethyleneimine / chemistry* Transfection* / methods
IF 4.556
リソース情報
ヒト・動物細胞 HuH-7(RCB1366)