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Fabrication of Novel Reduction‐ S ensitive Gene Vectors Based on Three‐ A rmed Peptides
Author(s) -
Lei Qi,
Sun YunXia,
Chen Si,
Qin SiYong,
Jia HuiZhen,
Zhuo RenXi,
Zhang XianZheng
Publication year - 2014
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201300422
Subject(s) - transfection , gene delivery , chemistry , dna , microbiology and biotechnology , cytotoxicity , hela , gene , plasmid , gene expression , intracellular , biophysics , in vitro , biochemistry , biology
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.