The role of cholesterol and structurally related molecules in enhancing transfection of cationic liposome-DNA complexes

Alexandra Zidovska, Heather M. Evans, Ayesha Ahmad, Kai K. Ewert, Cyrus R. Safinya

    Research output: Contribution to journalArticle

    Abstract

    Motivated by its important role in gene delivery, we have studied the effect of cholesterol and analogs on the transfection efficiency (TE) of lamellar cationic liposome-DNA (CL-DNA) complexes in vitro. Addition of cholesterol to low-transfecting DOTAP/DOPC-DNA complexes increases TE, with 15 mol % cholesterol already yielding 10-fold improvement. Steroids lacking the alkyl tail only modestly enhance TE, while molecules retaining it strongly enhance TE. All steroid-containing CL-DNA complexes exhibit the lamellar structure. The increase in experimentally determined membrane charge density (a universal parameter governing the TE of lamellar CL-DNA complexes) with cholesterol content alone cannot account for the rapid increase of TE. Instead, the reduction of the hydration repulsion layer of the membrane, caused by replacement of DOPC by cholesterol, promotes fusion between cationic membranes of CL-DNA complexes and anionic endosomal membranes, thus facilitating release of complexes and enhancing TE.

    Original languageEnglish (US)
    Pages (from-to)5208-5216
    Number of pages9
    JournalJournal of Physical Chemistry B
    Volume113
    Issue number15
    DOIs
    StatePublished - Apr 16 2009

    Fingerprint

    Liposomes
    Cholesterol
    cholesterol
    DNA
    deoxyribonucleic acid
    Molecules
    molecules
    membranes
    Membranes
    steroids
    Steroids
    Lamellar structures
    retaining
    Charge density
    Hydration
    genes
    hydration
    delivery
    Fusion reactions
    Genes

    ASJC Scopus subject areas

    • Physical and Theoretical Chemistry
    • Materials Chemistry
    • Surfaces, Coatings and Films

    Cite this

    The role of cholesterol and structurally related molecules in enhancing transfection of cationic liposome-DNA complexes. / Zidovska, Alexandra; Evans, Heather M.; Ahmad, Ayesha; Ewert, Kai K.; Safinya, Cyrus R.

    In: Journal of Physical Chemistry B, Vol. 113, No. 15, 16.04.2009, p. 5208-5216.

    Research output: Contribution to journalArticle

    Zidovska, Alexandra ; Evans, Heather M. ; Ahmad, Ayesha ; Ewert, Kai K. ; Safinya, Cyrus R. / The role of cholesterol and structurally related molecules in enhancing transfection of cationic liposome-DNA complexes. In: Journal of Physical Chemistry B. 2009 ; Vol. 113, No. 15. pp. 5208-5216.
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    AU - Safinya, Cyrus R.

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