Serum insensitive, intranuclear protein delivery by the multipurpose cationic lipid Saint-2

Bernardina T.F. van der Gun, Amélie Monami, Sven Laarmann, Tamás Raskó, Krystyna Ślaska-Kiss, Elmar Weinhold, Reinhold Wasserkort, Lou F.M.H. de Leij, Marcel H.J. Ruiters, Antal Kiss, Pamela M.J. McLaughlin

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Cationic liposomal compounds are widely used to introduce DNA and siRNA into viable cells, but none of these compounds are also capable of introducing proteins. Here we describe the use of a cationic amphiphilic lipid Saint-2:DOPE for the efficient delivery of proteins into cells (profection). Labeling studies demonstrated equal delivery efficiency for protein as for DNA and siRNA. Moreover, proteins complexed with Saint-2:DOPE were successfully delivered, irrespective of the presence of serum, and the profection efficiency was not influenced by the size or the charge of the protein:cationic liposomal complex. Using β-galactosidase as a reporter protein, enzymatic activity was detected in up to 98% of the adherent cells, up to 83% of the suspension cells and up to 70% of the primary cells after profection. A delivered antibody was detected in the cytoplasm for up to 7 days after profection. Delivery of the methyltransferase M.SssI resulted in DNA methylation, leading to a decrease in E-cadherin expression. The lipid-mediated multipurpose transport system reported here can introduce proteins into the cell with an equal delivery efficiency as for nucleotides. Delivery is irrespective of the presence of serum, and the protein can exert its function both in the cytoplasm and in the nucleus. Furthermore, DNA methylation by M.SssI delivery as a novel tool for gene silencing has potential applications in basic research and therapy.

Original languageEnglish
Pages (from-to)228-238
Number of pages11
JournalJournal of Controlled Release
Volume123
Issue number3
DOIs
Publication statusPublished - Nov 20 2007

Keywords

  • Cationic liposome
  • DNA methyltransferase
  • Gene silencing
  • Intracellular protein delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

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    van der Gun, B. T. F., Monami, A., Laarmann, S., Raskó, T., Ślaska-Kiss, K., Weinhold, E., Wasserkort, R., de Leij, L. F. M. H., Ruiters, M. H. J., Kiss, A., & McLaughlin, P. M. J. (2007). Serum insensitive, intranuclear protein delivery by the multipurpose cationic lipid Saint-2. Journal of Controlled Release, 123(3), 228-238. https://doi.org/10.1016/j.jconrel.2007.08.014