title: Fabrication of novel reduction-sensitive gene vectors based on three-armed peptides.
abstract: To address the inherent barriers of gene transfection, two reduction-sensitive branched polypeptides (RBPs) are synthesized and explored as novel non-viral gene vectors. The introduced disulfide linkages in RBPs facilitate glutathione-triggered intracellular gene release and reduce polymer degradation-induced cytotoxicity. Furthermore, the highly branched architecture concurrently realizes multivalency for strong DNA binding and elicits conformational flexibility for tight DNA compacting, which are beneficial for cellular entry. To increase the endosomal escape of plasmid DNA, pH-sensitive histidyl residues are incorporated into RBPs to improve buffer capacity in an acidic environment. In vitro study demonstrates that RBPs can efficiently mediate the DNA transfection and avoid apparent cytotoxicity in HeLa and COS7. The present gene delivery system offers a simple and flexible approach to fabricate microenvironment-specific branched gene vectors for gene therapy.
authors: Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.
authors: Qi
authors: Q
authors: Lei
authors: Yun-Xia
authors: YX
authors: Sun
authors: Si
authors: S
authors: Chen
authors: Si-Yong
authors: SY
authors: Qin
authors: Hui-Zhen
authors: HZ
authors: Jia
authors: Ren-Xi
authors: RX
authors: Zhuo
authors: Xian-Zheng
authors: XZ
authors: Zhang
mesh_terms: D004247:DNA / Q000737:chemistry / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D005978:Glutathione / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010455:Peptides / Q000737:chemistry / Q000235:genetics*; D011108:Polymers / Q000737:chemistry; D014162:Transfection
chemical_list: D010455:Peptides; D011108:Polymers; D004247:DNA; D005978:Glutathione
keywords: gene vectors; pH-sensitive; reduction-sensitive; three-armed peptides