Evaluation of polyether-polyethyleneimine graft copolymers as gene transfer agents

H. K. Nguyen, P. Lemieux, S. V. Vinogradov, Catherine L Gebhart, N. Guérin, G. Paradis, T. K. Bronich, V. Y. Alakhov, A. V. Kabanov

Research output: Contribution to journalArticlepeer-review

335 Scopus citations

Abstract

Cationic copolymers consisting of polycations linked to nonionic polymers are evaluated as non-viral gene delivery systems. These copolymers are known to produce soluble complexes with DNA, but only a few studies have characterized the transfection activity of these complexes. This work reports the synthesis and characterization of a series of cationic copolymers obtained by grafting the polyethyleneimine (PEI) with non-ionic polyethers, poly (ethylene oxide) (PEO) or Pluronic 123 (P123). The PEO-PEI conjugates differ in the molecular mass of PEI (2 kDa and 25 kDa) and the degree of modification of PEI with PEO. All of these conjugates form complexes upon mixing with plasmids, which are stable in aqueous dispersion for several days. The sizes of the particles formed in these systems vary from 70 to 200 nm depending on the composition of the complex. However, transfection activity of these systems is much lower than that of PEI (25 kDa) or Superfect as assessed in in vitro transfection experiments utilizing a luciferase reporter expression in Cos-7 cells as a model system. In contrast, conjugate of P123 with PEI (2 kDa) mixed with free P123 (9:1(wt)) forms small and stable complexes with DNA (110 nm) that exhibit high transfection activity in vitro. Furthermore, gene expression is observed in spleen, heart, lungs and liver 24 h after i.v. injection of this complex in mice. Compared to 1,2-bis(oleoyloxyl-(trimethylammonio) propane:cholesterol (DOTAP:Chol) and PEI (25 kDa) transfection systems, the P123-PEI system reveals a more uniform distribution of gene expression between these organs, allowing a significant improvement of gene expression in liver.

Original languageEnglish (US)
Pages (from-to)126-138
Number of pages13
JournalGene Therapy
Volume7
Issue number2
DOIs
StatePublished - Jan 2000

Keywords

  • Cationic copolymers
  • Gene expression
  • Non-viral
  • Polyethyleneimine

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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