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

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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.
LanguageEnglish
Pages125-140
Number of pages16
JournalPharmaceutics
Volume3
Issue number2
Early online date25 Mar 2011
DOIs
StatusPublished - Jun 2011

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Spermine
Gene Silencing
Amides
Small Interfering RNA
Fatty Acids
Unsaturated Fatty Acids
Cell Survival
Gene Knockdown Techniques
Polyamines
HeLa Cells
Nucleotides
Gene Expression
Serum

Cite this

Efficient gene silencing by self-assembled complexes of siRNA and symmetrical fatty acid amides of spermine. / Metwally, Abdelkader A; Pourzand, Charareh; Blagbrough, Ian A.

In: Pharmaceutics, Vol. 3, No. 2, 06.2011, p. 125-140.

Research output: Contribution to journalArticle

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