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 language | English |
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Pages (from-to) | 183-192 |
Number of pages | 10 |
Journal | Journal of Controlled Release |
Volume | 76 |
Issue number | 1-2 |
DOIs | |
State | Published - Sep 11 2001 |
Externally published | Yes |
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