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Structure-activity relationship study of dendritic polyglycerolamines for efficient siRNA transfection

Item Type:Article
Title:Structure-activity relationship study of dendritic polyglycerolamines for efficient siRNA transfection
Creators Name:Mehrabadi, F.S. and Hirsch, O. and Zeisig, R. and Posocco, P. and Laurini, E. and Pricl, S. and Haag, R. and Kemmner, W. and Calderon, M.
Abstract:Structure–activity relationship studies are pivotal in the development of existing small interfering RNA (siRNA) nanocarriers and in designing new delivery systems. In this paper, we investigated the ability of four dendritic polyglycerolamines (dPG-NH2) with increasing amine degree of functionalization (DF) on dendritic polyglycerol (dPG) to complex DNA by a coupled in silico/in vitro approach. In parallel, we examined our dPG-NH2 analogues for siRNA complexation, cytotoxicity, and transfection efficiency in vitro and in vivo. Our simulation data indicate the most effective nucleic acid affinities for dPG-NH2 analogues with DF >= 50%. Concomitantly, the results of in vitro and in vivo transfection studies also demonstrate efficient siRNA transfection only for those dPG-NH2 analogues with DF >= 50%. Thus, both MD simulation and siRNA knockdown studies show that a minimum DF per dPG unit (namely 50% on a 10 kDa dPG) is needed to achieve efficient siRNA interaction and successful transfection.
Keywords:Nucleic Acids, Structures (Built Objects), Degree of Functionalization, Delivery Systems, MD Simulation, Nano-Carriers, Simulation Data, Small Interfering RNA (siRNA), Structure Activity Relationships, Transfection Efficiency
Source:RSC Advances
Publisher:Royal Society of Chemistry
Page Range:78760-78770
Date:8 September 2015
Official Publication:https://doi.org/10.1039/C5RA10944B

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