Reducible Poly(amido ethylenimine)-Based Gene Delivery System for Improved Nucleus Trafficking of Plasmid DNA

• Published in: Bioconjugate chemistry Vol. 21; no. 2; pp. 296 - 301
• Main Authors: Jeong, Ji Hoon, Kim, Sun Hwa, Christensen, Lane V, Feijen, Jan, Kim, Sung Wan
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 17.02.2010
• Subjects: Acrylic Resins - chemistry; Active Transport, Cell Nucleus; Animals; Base Sequence; Buthionine Sulfoximine - chemistry; Carbocyanines - metabolism; Cell Nucleus - metabolism; Deoxyribonucleic acid; DNA; DNA - genetics; DNA - metabolism; Genes; Mice; NIH 3T3 Cells; Oxidation-Reduction; Plasmids - genetics; Polymerization; Polymers; Proteins; Transfection - methods
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc9003525

In a nonviral gene delivery system, localization of a plasmid DNA in the nucleus is a prerequisite for expression of a desired therapeutic protein encoded in the plasmid DNA. In this study, a reducible polymer-based gene delivery system for improved intracellular trafficking and nuclear translocation of plasmid DNA is introduced. The system is consisted of two components, a plasmid DNA having repeated binding sequence for a karyophilic protein, NFκB, and a reducible polymer. A reducible poly(amido ethylenimine), poly(TETA-CBA), was synthesized by a Michael-type addition polymerization between cystamine bisacrylamide and triethyl tetramine. The polymer forming tight complexes with plasmid DNA could be degraded in the reductive cytosol to release the plasmid DNA. The triggered release mechanism in the cytosol could facilitate the interaction between cytosolic NFκB and the plasmid DNA having repeated NFκB biding motif. Upon activation of NFκB by interleukin-1β (IL-1β), most of the plasmid distributed in the cytoplasm was localized within the nucleus, resulting in significantly higher gene transfection efficiency than controls with nondegradable PEI. The current study suggests an alternative way of improving transfection efficiency by taking advantage of endogenous transport machinery for intracellular trafficking and nuclear translocation of a plasmid DNA.