Gene delivery by cationic lipids: in and out of an endosome

D. Hoekstra*, J. Rejman, L. Wasungu, F. Shi, I. Zuhorn

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

144 Citations (Scopus)

Abstract

Cationic lipids are exploited as vectors ('lipoplexes') for delivering nucleic acids, including genes, into cells for both therapeutic and cell biological purposes. However, to meet therapeutic requirements, their efficacy needs major improvement, and better defining the mechanism of entry in relation to eventual transfection efficiency could be part of such a strategy. Endocytosis is the major pathway of entry, but the relative contribution of distinct endocytic pathways, including clathrin- and caveolae-mediated endocytosis and/or macropinocytosis is as yet poorly defined. Escape of DNA/RNA from endosomal compartments is thought to represent a major obstacle. Evidence is accumulating that non-lamellar phase changes of the lipoplexes, facilitated by intracellular lipids, which allow DNA to dissociate from the vector and destabilize endosomal membranes, are instrumental in plasmid translocation into the cytosol, a prerequisite for nuclear delivery. To further clarify molecular mechanisms and to appreciate and overcome intracellular hurdles in lipoplex-mediated gene delivery, quantification of distinct steps in overall transfection and proper model systems are required.

Original languageEnglish
Pages (from-to)68-71
Number of pages4
JournalBiochemical Society Transactions
Volume35
Publication statusPublished - Feb-2007
EventConference on Cellular Delivery of Therapeutic Macromolecules -
Duration: 29-Aug-200631-Aug-2006

Keywords

  • cationic lipid
  • endocytosis
  • gene delivery
  • hexagonal phase
  • lipoplex
  • transfection
  • CAVEOLAE-MEDIATED ENDOCYTOSIS
  • INTRACELLULAR TRAFFICKING
  • TRANSFECTION EFFICIENCY
  • DNA COMPLEXES
  • MAMMALIAN-CELLS
  • PHASE
  • LIPOPLEXES
  • CLATHRIN
  • POLYPLEXES
  • MECHANISM

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