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

Fingerprint

Transfection
Lipids
Genes
Serum
Plasmids
DNA
Serum-Free Culture Media
Micelles
Nucleic Acids
Cell Survival

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

Cite this

Candiani, G., Pezzoli, D., Cabras, M., Ristori, S., Pellegrini, C., Kajaste-Rudnitski, A., ... 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

A dimerizable cationic lipid with potential for gene delivery. / Candiani, Gabriele; Pezzoli, Daniele; Cabras, Mariasara; Ristori, Sandra; Pellegrini, Cinzia; Kajaste-Rudnitski, Anna; Vicenzi, Elisa; Sala, Carlo; Zanda, Matteo.

In: The Journal of Gene Medicine, Vol. 10, No. 6, 01.06.2008, p. 637-645.

Research output: Contribution to journalArticle

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, vol. 10, no. 6, pp. 637-645. https://doi.org/10.1002/jgm.1186
Candiani G, Pezzoli D, Cabras M, Ristori S, Pellegrini C, Kajaste-Rudnitski A et al. A dimerizable cationic lipid with potential for gene delivery. The Journal of Gene Medicine. 2008 Jun 1;10(6):637-645. https://doi.org/10.1002/jgm.1186
Candiani, Gabriele ; Pezzoli, Daniele ; Cabras, Mariasara ; Ristori, Sandra ; Pellegrini, Cinzia ; Kajaste-Rudnitski, Anna ; Vicenzi, Elisa ; Sala, Carlo ; Zanda, Matteo. / A dimerizable cationic lipid with potential for gene delivery. In: The Journal of Gene Medicine. 2008 ; Vol. 10, No. 6. pp. 637-645.
@article{48554386059d4b68a9c78ff65f7a3a30,
title = "A dimerizable cationic lipid with potential for gene delivery",
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.",
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",
author = "Gabriele Candiani and Daniele Pezzoli and Mariasara Cabras and Sandra Ristori and Cinzia Pellegrini and Anna Kajaste-Rudnitski and Elisa Vicenzi and Carlo Sala and Matteo Zanda",
year = "2008",
month = "6",
day = "1",
doi = "10.1002/jgm.1186",
language = "English",
volume = "10",
pages = "637--645",
journal = "The Journal of Gene Medicine",
issn = "1099-498X",
publisher = "John Wiley and Sons Ltd",
number = "6",

}

TY - JOUR

T1 - A dimerizable cationic lipid with potential for gene delivery

AU - Candiani, Gabriele

AU - Pezzoli, Daniele

AU - Cabras, Mariasara

AU - Ristori, Sandra

AU - Pellegrini, Cinzia

AU - Kajaste-Rudnitski, Anna

AU - Vicenzi, Elisa

AU - Sala, Carlo

AU - Zanda, Matteo

PY - 2008/6/1

Y1 - 2008/6/1

N2 - 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.

AB - 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.

KW - analysis of variance

KW - animals

KW - COS cells

KW - cations

KW - cell line, tumor

KW - cercopithecus aethiops

KW - DNA

KW - dimerization

KW - fluorometry

KW - gene transfer techniques

KW - humans

KW - lipids

KW - micelles

KW - molecular structure

KW - rats

KW - triazines

KW - dimerizable function

KW - gene delivery

KW - lipoplex

KW - nonviral vector

KW - serum effect

KW - transfection

U2 - 10.1002/jgm.1186

DO - 10.1002/jgm.1186

M3 - Article

VL - 10

SP - 637

EP - 645

JO - The Journal of Gene Medicine

JF - The Journal of Gene Medicine

SN - 1099-498X

IS - 6

ER -