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. SafinyaEmail author
Part of the Topics in Current Chemistry book series (TOPCURRCHEM, volume 296)


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.


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





Cationic liposome


Lipid with dendritic headgroup










Mouse embryonic fibroblast


Multivalent lipid


Nucleic acid


Neutral lipid


Poly(ethylene glycol)




RNA interference


Silencing efficiency


Short interfering RNA


Transfection efficiency


Univalent lipid


X-ray diffraction



KKE, AZ, AA, NFB, HME, and CRS were supported primarily by NIH GM-59288-11 and in part, by DOE-BES grant DE-FG02-06ER46314 (lipid microstructure) and NSF-DMR 0803103 (lipid phase behavior). CSM and CES were supported by NIH AI-12520 and AI-20611. Cryo-TEM experiments were conducted at the National Resource for Automated Molecular Microscopy which is supported by the National Institutes of Health though the National Center for Research Resources’ P41 program (RR17573). The X-ray diffraction work was carried out at the Stanford Synchrotron Radiation Laboratory which is supported by the Department of Energy.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Kai K. Ewert
    • 1
  • Alexandra Zidovska
    • 1
    • 2
  • Ayesha Ahmad
    • 1
    • 3
  • Nathan F. Bouxsein
    • 1
  • Heather M. Evans
    • 1
    • 4
  • Christopher S. McAllister
    • 5
    • 6
  • Charles E. Samuel
    • 5
  • Cyrus R. Safinya
    • 1
    Email author
  1. 1.Physics, Materials & Molecular, Cellular and Developmental Biology DepartmentUniversity of California at Santa BarbaraSanta BarbaraUSA
  2. 2.Department of Systems BiologyHarvard Medical SchoolBostonUSA
  3. 3.Dynavax TechnologiesBerkeleyUSA
  4. 4.National Nanotechnology Coordination OfficeWashingtonUSA
  5. 5.Molecular, Cellular and Developmental Biology Department & Biomolecular Science and Engineering ProgramUniversity of California at Santa BarbaraSanta BarbaraUSA
  6. 6.Department of MedicineUniversity of CaliforniaSan DiegoUSA

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