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


Reference:

Metwally, A. A., Pourzand, C. and Blagbrough, I. A., 2011. Efficient gene silencing by self-assembled complexes of siRNA and symmetrical fatty acid amides of spermine. Pharmaceutics, 3 (2), pp. 125-140.

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    Official URL:

    http://dx.doi.org/10.3390/pharmaceutics3020125

    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.

    Details

    Item Type Articles
    CreatorsMetwally, A. A., Pourzand, C. and Blagbrough, I. A.
    DOI10.3390/pharmaceutics3020125
    DepartmentsFaculty of Science > Pharmacy & Pharmacology
    Publisher StatementPharmaceutics_2011_3_125-140_AAM_CP_ISB.pdf: This is an Open Access article, provided under a Creative Commons Attribution Licence. The full citation for this article is: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. DOI: http://dx.doi.org/10.3390/pharmaceutics3020125
    RefereedYes
    StatusPublished
    ID Code24924

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