Cationic liposome-nucleic acid complexes for gene delivery and silencing: Pathways and mechanisms for plasmid DNA and siRNA

Kai K. Ewert, Alexandra Zidovska, Ayesha Ahmad, Nathan F. Bouxsein, Heather M. Evans, Christopher S. McAllister, Charles E. Samuel, Cyrus R. Safinya

    Research output: Chapter in Book/Report/Conference proceedingChapter

    Abstract

    Motivated by the promises of gene therapy, there is great interest in developing non-viral lipid-based vectors for therapeutic applications due to their low immunogenicity, low toxicity, ease of production, and the potential of transferring large pieces of DNA into cells. In fact, cationic liposome (CL) based vectors are among the prevalent synthetic carriers of nucleic acids (NAs) currently used in gene therapy clinical trials worldwide. These vectors are studied both for gene delivery with CL-DNA complexes and gene silencing with CL-siRNA (short interfering RNA) complexes. However, their transfection efficiencies and silencing efficiencies remain low compared to those of engineered viral vectors. This reflects the currently poor understanding of transfection-related mechanisms at the molecular and self-assembled levels, including a lack of knowledge about interactions between membranes and double stranded NAs and between CL-NA complexes and cellular components. In this review we describe our recent efforts to improve the mechanistic understanding of transfection by CL-NA complexes, which will help to design optimal lipid-based carriers of DNA and siRNA for therapeutic gene delivery and gene silencing.

    Original languageEnglish (US)
    Title of host publicationNucleic Acid Transfection
    EditorsWolfgang Bielke, Christoph Erbacher
    Pages191-226
    Number of pages36
    DOIs
    StatePublished - Nov 29 2010

    Publication series

    NameTopics in Current Chemistry
    Volume296
    ISSN (Print)0340-1022

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    Keywords

    • Cholesterol
    • Gene delivery
    • Multivalent cationic lipid
    • Small angle X-ray scattering
    • siRNA

    ASJC Scopus subject areas

    • Chemistry(all)

    Cite this

    Ewert, K. K., Zidovska, A., Ahmad, A., Bouxsein, N. F., Evans, H. M., McAllister, C. S., Samuel, C. E., & Safinya, C. R. (2010). Cationic liposome-nucleic acid complexes for gene delivery and silencing: Pathways and mechanisms for plasmid DNA and siRNA. In W. Bielke, & C. Erbacher (Eds.), Nucleic Acid Transfection (pp. 191-226). (Topics in Current Chemistry; Vol. 296). https://doi.org/10.1007/128_2010_70