H. Lee et al., A new gene delivery formulation of polyethylenimine/DNA complexes coated with PEG conjugated fusogenic peptide, J CONTR REL, 76(1-2), 2001, pp. 183-192
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 sp
ecific derivative, was reacted with KALA to produce a PEG-KALA conjugate. T
he conjugate was analyzed by matrix-assisted laser desorption ionization ti
me-of-flight mass spectrometry, and its hemolytic activity was determined r
elative to KALA. Positively charged PEG-KALA conjugate was coated onto the
surface of negatively charged DNA/PEI complexes to form net positively char
ged PEG-KALA/DNA/PEI complexes. They were 200-400 nm in diameter with incre
asing amount of PEG-KALA, whereas DNA/PEI complexes coated with KALA aggreg
ated to a great extent. This was because PEG chains surrounding the surface
of the complexes suppressed the inter-particle interaction that was mediat
ed by cationic KALA. Transfection efficiency progressively increased as the
amount of PEG-KALA to be coated was increased, suggesting that fusogenic a
ctivity of KALA contributes to enhancing the level of gene expression. (C)
2001 Elsevier Science B.V. All rights reserved.