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
JournalJournal of Gene Medicine
Volume10
Issue number6
DOIs
Publication statusPublished - Jun 2008

Fingerprint

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

Keywords

  • Dimerizable function
  • Gene delivery
  • Lipoplex
  • Nonviral vector
  • Serum effect
  • Transfection

ASJC Scopus subject areas

  • Genetics

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. 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: Journal of Gene Medicine, Vol. 10, No. 6, 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', 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. Journal of Gene Medicine. 2008 Jun;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: Journal of Gene Medicine. 2008 ; Vol. 10, No. 6. pp. 637-645.
@article{682b76c195444d1498c812f11c68b390,
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 = "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",
doi = "10.1002/jgm.1186",
language = "English",
volume = "10",
pages = "637--645",
journal = "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

Y1 - 2008/6

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 - Dimerizable function

KW - Gene delivery

KW - Lipoplex

KW - Nonviral vector

KW - Serum effect

KW - Transfection

UR - http://www.scopus.com/inward/record.url?scp=46649104752&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=46649104752&partnerID=8YFLogxK

U2 - 10.1002/jgm.1186

DO - 10.1002/jgm.1186

M3 - Article

C2 - 18338839

AN - SCOPUS:46649104752

VL - 10

SP - 637

EP - 645

JO - Journal of Gene Medicine

JF - Journal of Gene Medicine

SN - 1099-498X

IS - 6

ER -