Gene Ther 1998 Mar 01;53:409-14. doi: 10.1038/sj.gt.3300606.

Chloroquine and amphipathic peptide helices show synergistic transfection in vitro.

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A pH-responsive peptide fragment modelled on the influenza virus haemagglutinin (INF7-SGSC) can promote the transfectional activity of poly(L)-lysine (pLL)/DNA complexes against 293 cells. Chloroquine also promotes transfection, but the combination of INF7-SGSC and chloroquine gives an increased, synergistic, transfectional activity. This was unexpected since the supposed modes of action of these two agents are expected to be incompatible. Microinjection of pLL/DNA complexes into the cytoplasm of Xenopus oocytes produced greater gene expression than microinjection of free DNA, possibly reflecting nuclear-homing or protection from degradation by cytoplasmic nucleases. However, pretreatment of complexes with INF7-SGSC (but not chloroquine) before cytoplasmic microinjection promoted gene expression still further. When pLL/DNA complexes were injected directly into the nucleus, INF7-SGSC again increased gene expression. The mechanism of post-endosomal action of INF7-SGSC is unknown, but could reflect its polyanionic nature, possibly enhancing intranuclear dissociation of the complexes. Whatever the mechanism, it appears that INF7-SGSC mediates two effects-one probably endosomal and the second post-endosomal, the latter showing a synergistic transfection interaction with chloroquine.

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