title: Nanosized, peptide-based multicomponent DNA delivery systems: optimization of endosome escape activity.
abstract: OBJECTIVE
  Endosome escape is essential for developing effective nonviral gene delivery systems. Herein, three endosome-disrupting peptides (HA2(1-20), GALA and KALA) were incorporated into a multicomponent oligonucleotide delivery system to identify which peptide imparted the most favorable endosome escape and toxicity profile.
  
  
  METHODS
  Copper (I)-catalyzed azide-alkyne cycloaddition was used to construct multicomponent delivery vectors. The systems were evaluated for size, toxicity, cellular uptake and endosome escape activity.
  
  
  RESULTS
  Each system condensed plasmid DNA to form nanosized particles. The highest cellular uptake and endosome escape were associated with GALA and KALA containing systems, with KALA incorporation correlating with greater toxicity.
  
  
  CONCLUSIONS
  GALA was selected as the most promising endosome-disrupting peptide for incorporation into the nanosized oligonucleotide delivery system.
authors.affiliation: School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia, 4072, QLD, Australia.|School of Pharmacy, The University of Queensland, Woolloongabba, 4102, QLD, Australia.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wan
authors.affiliation: School of Pharmacy, The University of Queensland, Woolloongabba, 4102, QLD, Australia.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Moyle
authors.affiliation: School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia, 4072, QLD, Australia.
authors.forename: Michelle P
authors.initials: MP
authors.lastname: Christie
authors.affiliation: School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia, 4072, QLD, Australia.|School of Pharmacy, The University of Queensland, Woolloongabba, 4102, QLD, Australia.|Institute for Molecular Bioscience, The University of Queensland, St Lucia, 4072, QLD, Australia.
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
mesh_terms: D000595:Amino Acid Sequence; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics; D011992:Endosomes / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics; D014162:Transfection / Q000379:methods
chemical_list: D010455:Peptides; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004247:DNA
keywords: GALA; KALA; TAT; cell-penetrating peptides; endosome escape; fusogenic peptides; gene therapy; nonviral gene delivery; poly-L-lysine