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Title:Reconfiguring the side-chain functionality of cationic helical polypeptides toward maximized gene delivery capabilities
Author(s):Zhang, Rujing
Advisor(s):Cheng, Jianjun
Department / Program:Materials Science & Engineerng
Discipline:Materials Science & Engr
Degree Granting Institution:University of Illinois at Urbana-Champaign
gene delivery
helical structure
Abstract:The rational design of effective and safe non-viral gene vectors is largely dependent on the understanding of the structure-property relationship. This thesis aims to report the design of a new series of cationic, α-helical polypeptides with different side charged groups (amine and guanidine) and hydrophobicity, and to mechanistically unravel 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 LipofectamineTM 2000 (LPF2000) by 3-6 folds. This study thus provides mechanistic insights into the rational design of non-viral gene delivery vectors, and the top-performing materials identified also serve as promising additions to the existing systems.
Issue Date:2014-01-16
Rights Information:Copyright 2013 Rujing Zhang
Date Available in IDEALS:2014-01-16
Date Deposited:2013-12

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