Nonbilayer phase of lipoplex-membrane mixture determines endosomal escape of genetic cargo and transfection efficiency.
作者： Inge S. Zuhorn , Udo Bakowsky , Evgeny Polushkin , Willy H. Visser , Marc C.A. Stuart
DOI: 10.1016/J.YMTHE.2004.12.018
关键词:
摘要: Cationic lipids are widely used for gene delivery, and inclusion of dioleoylphosphatidylethanolamine (DOPE) as a helper lipid in cationic lipid-DNA formulations often promotes transfection efficacy. To investigate the significance DOPE's preference to adopt hexagonal phase mechanism transfection, properties efficiencies SAINT-2/DOPE lipoplexes were compared those containing lamellar-phase-forming dipalmitoylphosphatidylethanolamine (DPPE). After interaction with anionic vesicles, simulate lipoplex-endosomal membrane interaction, show perfect phase, whereas SAINT-2/DPPE form mixed lamellar-hexagonal phase. The transition is crucial dissociation DNA or oligonucleotides (ODN) from lipoplexes. However, while nucleic acid release either complex similar, displayed two- threefold higher efficiency nuclear ODN delivery. Interestingly, rupture endosomes following cellular incubation ODN-containing complexes dramatically improved delivery level that was similar observed complexes. Our data demonstrate although formation prerequisite complex, it appears highly critical accomplishing efficient translocation acids across endosomal into cytosol transport nucleus.
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