• Submit to Pharmaceutics Login Register
• MDPI
• Journals A-Z
• For Authors
• For Editors
• About
• Open Access Policy

• Abstract
• Full-Text PDF [401 KB]
• Full-Text XML
• Article Versions Notes

• Article Statistics
• Google Scholar
• Order Reprints

• Cite this article
• Export to BibTeX
• Export to EndNote

• [+] on DOAJ
• Metwally, A
• Pourzand, C
• Blagbrough, I
• [+] on Google Scholar
• Metwally, A
• Pourzand, C
• Blagbrough, I
• [+] on PubMed
• Metwally, A
• Pourzand, C
• Blagbrough, I

•  CiteULike
•  Facebook
•  Mendeley
•  Twitter

This article is

• freely available
• re-usable

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

Article

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

Abdelkader A. Metwally, Charareh Pourzand and Ian S. Blagbrough*

Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK

* Author to whom correspondence should be addressed.

Received: 28 January 2011; in revised form: 11 March 2011 / Accepted: 22 March 2011 / Published: 25 March 2011

(This article belongs to the Special Issue Delivery and Genomics of Large Molecules)

Download PDF Full-Text [401 KB, Updated Version, uploaded 28 March 2011 12:19 CEST]

The original version is still available [1050 KB, uploaded 25 March 2011 12:13 CET]

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.

Keywords: fatty acids; gene silencing; GFP; lipoplexes; self-assembly; siRNA; spermine

Article Statistics

Cite This Article