Efficient escape from endosomes determines the superior efficiency of multicomponent lipoplexes.
Designer multicomponent lipoplexes have recently emerged as especially promising transfection candidates, since they are from 10 to 100 times more efficient than binary complexes usually employed for gene delivery purposes. Here, we show, for the first time, that after internalization binary complexes of lower transfection potency remain in compact perinuclear endosomes, while multicomponent systems have intrinsic endosomal rupture properties that allow plasmid DNA to escape from endosomes with extremely high efficiency. Endosomal rupture results in an extraordinarily homogeneous distribution of unbound plasmid DNA throughout the cytoplasm and in the nucleus.
Caracciolo
Giulio
G
Department of Chemistry, 'Sapienza' University of Rome, P.le A. Moro 5, 00185 Rome, Italy. g.caracciolo@caspur.it
Caminiti
Ruggero
R
Digman
Michelle A
MA
Gratton
Enrico
E
Sanchez
Susana
S
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection
D008081:Liposomes; D004247:DNA