Reconfiguring the side-chain functionality of cationic helical polypeptides toward maximized gene delivery capabilities
Zhang, Rujing
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https://hdl.handle.net/2142/46865
Description
Title
Reconfiguring the side-chain functionality of cationic helical polypeptides toward maximized gene delivery capabilities
Author(s)
Zhang, Rujing
Issue Date
2014-01-16T18:19:05Z
Director of Research (if dissertation) or Advisor (if thesis)
Cheng, Jianjun
Department of Study
Materials Science & Engineerng
Discipline
Materials Science & Engr
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
M.S.
Degree Level
Thesis
Keyword(s)
polypeptides
gene delivery
guanidine
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.
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