Dequalinium TM Vesicles Form Stable Complexes with Plasmid DNA which Are Protected from DNase Attack
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J. Lasch
Abstract
Upon sonication, the antimicrobial and antineoplastic compound dequaliniumTM forms vesicles (DQAsomes, Weissig et al., 1998). DequaliniumTM (1,1′-(1,10-decamethylene-bis-[aminoquinaldinium])-chloride) was shown to be a fluorophore with an emission maximum at 366 nm. Addition of DNA results in a characteristic quenching of its intrinsic fluorescence. After density gradient centrifugation a band of dequaliniumTM (DQA) tightly associated with DNA is located between the DNA and DQA bands. DQA/DNA-complexes containing plasmid DNA at a molar ratio of DQA/DNA 6:1 are completely protected against DNase activity. Addition of negatively-charged lipids release intact DNA in the same manner as from cationic lipid/DNA complexes. As regards biological effects, DQAsomes show a differential cytotoxicity for normal and sarcoma cell lines. In vitro incubation with fluorescein-labeled oligodeoxynucleotides (5′-fluorescein-[GATC]5) showed an increased uptake of the tagged oligodeoxynucleotide if complexed with dequalinium.
We hypothesize that the DQA/DNA complexes are well-suited for ‘DQAsomal gene transfer’ in vitro and in vivo. Noteworthy, they display an intrinsic antitumor activity manifested by differential cytotoxicity for normal and sarcoma cells.
Copyright © 1999 by Walter de Gruyter GmbH & Co. KG
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- Michael Strauss. January 12, 1950 April 29, 1999
- Monoallelic Expression of Pax5: A Paradigm for the Haploinsufficiency of Mammalian Pax Genes?
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