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Formulations which increase the size of lipoplexes prevent serum-associated inhibition of transfection.

Publication ,  Journal Article
Turek, J; Dubertret, C; Jaslin, G; Antonakis, K; Scherman, D; Pitard, B
Published in: J Gene Med
2000

BACKGROUND: Cationic lipids are the most widely used nonviral vectors for gene delivery. Upon complexation to DNA, they offer a nonimmunogenic alternative to viral gene transfer. Unfortunately, their in vivo application has been limited due to a serum-associated inhibition of transfection. As a result, significant research effort has focused on overcoming this deleterious effect of serum. METHODS: To better understand this phenomenon, we investigated the influence of lipoplex colloidal stability on gene transfection in the presence of serum. In addition, conditions of the reaction medium were modulated and their effects on collidal stability and subsequent in vitro transfection efficiency were studied. RESULTS: The colloidal stability of the cationic lipid-DNA complexes, which depended on the charge ratio, determined the efficiency of in vitro transfection in the presence of serum. In particular, large-sized, colloidally unstable complexes of over 700 nm mean diameter induced efficient transfection in the presence or absence of serum. Conversely, colloidally stable complexes of less than 250 nm in size resulted in efficient transfection only in the absence of serum. Furthermore, for the same charge ratio, both colloidally stable and unstable lipoplexes could be obtained depending on the degree to which various solution parameters (NaCl concentration, cationic lipid acyl chain length, pH and DNA concentration) were altered. In each case, only those complexes lacking colloidal stability resulted in high levels of in vitro transfection in the presence of serum. This phenomenon was shown to be independent of both the percent DNA internalized and of the lamellar organization of the cationic lipid/DNA lipoplexes. CONCLUSIONS: Through the modulation of various mixture conditions, large-sized lipoplexes can be formed which are resistant to the transfection-inhibiting effect of serum.

Duke Scholars

Published In

J Gene Med

DOI

ISSN

1099-498X

Publication Date

2000

Volume

2

Issue

1

Start / End Page

32 / 40

Location

England

Related Subject Headings

  • Transfection
  • Sodium Chloride
  • Scattering, Radiation
  • Plasmids
  • Mice
  • Luciferases
  • Lipids
  • Light
  • Hydrogen-Ion Concentration
  • Humans
 

Citation

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Turek, J., Dubertret, C., Jaslin, G., Antonakis, K., Scherman, D., & Pitard, B. (2000). Formulations which increase the size of lipoplexes prevent serum-associated inhibition of transfection. J Gene Med, 2(1), 32–40. https://doi.org/10.1002/(SICI)1521-2254(200001/02)2:1<32::AID-JGM78>3.0.CO;2-U
Turek, J., C. Dubertret, G. Jaslin, K. Antonakis, D. Scherman, and B. Pitard. “Formulations which increase the size of lipoplexes prevent serum-associated inhibition of transfection.J Gene Med 2, no. 1 (2000): 32–40. https://doi.org/10.1002/(SICI)1521-2254(200001/02)2:1<32::AID-JGM78>3.0.CO;2-U.
Turek J, Dubertret C, Jaslin G, Antonakis K, Scherman D, Pitard B. Formulations which increase the size of lipoplexes prevent serum-associated inhibition of transfection. J Gene Med. 2000;2(1):32–40.
Turek, J., et al. “Formulations which increase the size of lipoplexes prevent serum-associated inhibition of transfection.J Gene Med, vol. 2, no. 1, 2000, pp. 32–40. Pubmed, doi:10.1002/(SICI)1521-2254(200001/02)2:1<32::AID-JGM78>3.0.CO;2-U.
Turek J, Dubertret C, Jaslin G, Antonakis K, Scherman D, Pitard B. Formulations which increase the size of lipoplexes prevent serum-associated inhibition of transfection. J Gene Med. 2000;2(1):32–40.
Journal cover image

Published In

J Gene Med

DOI

ISSN

1099-498X

Publication Date

2000

Volume

2

Issue

1

Start / End Page

32 / 40

Location

England

Related Subject Headings

  • Transfection
  • Sodium Chloride
  • Scattering, Radiation
  • Plasmids
  • Mice
  • Luciferases
  • Lipids
  • Light
  • Hydrogen-Ion Concentration
  • Humans