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Pharmaceutics 2011, 3(2), 125-140; doi:10.3390/pharmaceutics3020125

Efficient Gene Silencing by Self-Assembled Complexes of siRNA and Symmetrical Fatty Acid Amides of Spermine

Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK
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Received: 28 January 2011 / Revised: 11 March 2011 / Accepted: 22 March 2011 / Published: 25 March 2011
(This article belongs to the Special Issue Delivery and Genomics of Large Molecules)
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Abstract

Gene silencing by siRNA (synthetic dsRNA of 21-25 nucleotides) is a well established biological tool in gene expression studies and has a promising therapeutic potential for difficult-to-treat diseases. Five fatty acids of various chain length and oxidation state (C12:0, C18:0, C18:1, C18:2, C22:1) were conjugated to the naturally occurring polyamine, spermine, and evaluated for siRNA delivery and gene knock-down. siRNA delivery could not be related directly to gene silencing efficiency as N4,N9-dierucoyl spermine resulted in higher siRNA delivery compared to N4,N9-dioleoyl spermine. GFP silencing in HeLa cells showed that the unsaturated fatty acid amides are more efficient than saturated fatty acid amides, with N4,N9-dioleoyl spermine resulting in the most efficient gene silencing in the presence of serum. The alamarBlue cell viability assay showed that fatty acid amides of spermine have good viability (75%–85% compared to control) except N4,N9-dilauroyl spermine which resulted in low cell viability. These results prove that unsaturated fatty acid amides of spermine are efficient, non-toxic, non-viral vectors for siRNA mediated gene silencing. View Full-Text
Keywords: fatty acids; gene silencing; GFP; lipoplexes; self-assembly; siRNA; spermine fatty acids; gene silencing; GFP; lipoplexes; self-assembly; siRNA; spermine
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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Metwally, A.A.; Pourzand, C.; Blagbrough, I.S. Efficient Gene Silencing by Self-Assembled Complexes of siRNA and Symmetrical Fatty Acid Amides of Spermine. Pharmaceutics 2011, 3, 125-140.

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