Journal
BIOMATERIALS
Volume 35, Issue 10, Pages 3443-3454Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.12.097
Keywords
Non-viral gene delivery; alpha-Helical polypeptide; Guanidine; Hydrophobicity; Structure-function relationship
Funding
- NSF [CHE-1153122]
- NIH [1DP2OD007246, 1R21EB013379]
- CABPN [I/UCRC NSF A1422]
- Division Of Chemistry
- Direct For Mathematical & Physical Scien [1153122] Funding Source: National Science Foundation
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The rational design of effective and safe non-viral gene vectors is largely dependent on the understanding of the structure-property relationship. We herein report the design of a new series of cationic, alpha-helical polypeptides with different side charged groups (amine and guanidine) and hydrophobicity, and mechanistically unraveled the effect of polypeptide structure on the gene delivery capability. Guanidine-containing polypeptides displayed superior membrane activities to their amine-containing analogues via the pore formation mechanism, and thus possessed notably higher transfection efficiencies. Elongating the hydrophobic side chain also potentiated the membrane activities of the polypeptides, while at the meantime caused higher cytotoxicities. Upon an optimal balance between membrane activity and cytotoxicity, maximal transfection efficiency was achieved which outperformed commercial reagent Lipofectamine (TM) 2000 (LPF2000) by 3-6 folds. This study thus provides mechanistic insights into the rational design of non-viral gene delivery vectors, and the best-performing materials identified also serve as a promising addition to the existing systems. (C) 2014 Elsevier Ltd. All rights reserved.
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