Efficient gene silencing by self-assembled complexes of siRNA and symmetrical fatty acid amides of spermine

Abdelkader A Metwally, Charareh Pourzand, Ian A Blagbrough

Research output: Contribution to journalArticle

8 Citations (Scopus)
129 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)125-140
Number of pages16
JournalPharmaceutics
Volume3
Issue number2
Early online date25 Mar 2011
DOIs
Publication statusPublished - Jun 2011

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