A new gene delivery formulation of polyethylenimine/DNA complexes coated with PEG conjugated fusogenic peptide

Haeshin Lee, Ji Hoon Jeong, Tae Gwan Park

Research output: Contribution to journalArticlepeer-review

141 Scopus citations

Abstract

A fusogenic peptide, KALA, was conjugated with poly(ethylene glycol) (PEG) for use as an endosome disruptive agent in the gene delivery formulation of polyethyleneimine (PEI). A maleimide terminated methoxy-PEG, a cysteine specific derivative, was reacted with KALA to produce a PEG-KALA conjugate. The conjugate was analyzed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, and its hemolytic activity was determined relative to KALA. Positively charged PEG-KALA conjugate was coated onto the surface of negatively charged DNA/PEI complexes to form net positively charged PEG-KALA/DNA/PEI complexes. They were 200-400 nm in diameter with increasing amount of PEG-KALA, whereas DNA/PEI complexes coated with KALA aggregated to a great extent. This was because PEG chains surrounding the surface of the complexes suppressed the inter-particle interaction that was mediated by cationic KALA. Transfection efficiency progressively increased as the amount of PEG-KALA to be coated was increased, suggesting that fusogenic activity of KALA contributes to enhancing the level of gene expression.

Original languageEnglish
Pages (from-to)183-192
Number of pages10
JournalJournal of Controlled Release
Volume76
Issue number1-2
DOIs
StatePublished - Sep 11 2001
Externally publishedYes

Funding

This work was supported by the Ministry of Health and Welfare, Korea (HMP-99-B-02-0002).

Keywords

  • DNA delivery
  • KALA
  • Non-viral vector
  • PEG
  • PEI

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