A dimerizable cationic lipid with potential for gene delivery

Gabriele Candiani, Daniele Pezzoli, Mariasara Cabras, Sandra Ristori, Cinzia Pellegrini, Anna Kajaste-Rudnitski, Elisa Vicenzi, Carlo Sala, Matteo Zanda

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

BACKGROUND: Despite the use of currently optimized lipofection conditions, including transfection in serum-depleted media, the efficiency of gene transfer is low and high transfection rates often induce cytotoxicity. A lipid formulation with transfection efficiency not inhibited by serum would provide an advance towards in vivo applications. METHODS: We explored the ability of the cationic lipid SH-14 to dimerize upon DNA and form lipoplexes, and potentially release nucleic acids in the intracellular reducing milieu. We investigated the critical micelle-forming concentration of SH-14 and its intrinsic toxicity, size and Zeta potential measurements, the in vitro cytotoxicity of SH-14/plasmid DNA lipoplexes and their ability to transfect cells. RESULTS: Among all the charge ratios (CR, + /-) tested, lipoplexes at CR 10 with a mean diameter of 295 nm and a surface charge of + 20 mV, exhibited the best compromise between transfection efficiency and tolerability. SH-14 presented the same cytotoxicity level whether alone or complexed in lipoplexes. Lipofections carried out in serum-free medium shared a transfection efficiency, on average, of 40% and a cytotoxicity of 38%. An increase of 73% in transfection efficiency and 24% in cell viability were obtained, extending lipofection over 48 h in complete-medium. Moreover, when serum concentration was increased from 10% to 50%, a three-fold increase in plasmid dose led to more than 72% of cells being transfected with almost no sign of cytotoxicity. CONCLUSIONS: Overall, SH-14 presents good potential as a novel transfection reagent to be used in the presence of serum.
Original languageEnglish
Pages (from-to)637-645
Number of pages9
JournalThe Journal of Gene Medicine
Volume10
Issue number6
Early online date14 Mar 2008
DOIs
Publication statusPublished - 1 Jun 2008

Keywords

  • analysis of variance
  • animals
  • COS cells
  • cations
  • cell line, tumor
  • cercopithecus aethiops
  • DNA
  • dimerization
  • fluorometry
  • gene transfer techniques
  • humans
  • lipids
  • micelles
  • molecular structure
  • rats
  • triazines
  • dimerizable function
  • gene delivery
  • lipoplex
  • nonviral vector
  • serum effect
  • transfection

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  • Cite this

    Candiani, G., Pezzoli, D., Cabras, M., Ristori, S., Pellegrini, C., Kajaste-Rudnitski, A., Vicenzi, E., Sala, C., & Zanda, M. (2008). A dimerizable cationic lipid with potential for gene delivery. The Journal of Gene Medicine, 10(6), 637-645. https://doi.org/10.1002/jgm.1186