title: Intranuclear DNA release is a determinant of transfection activity for a non-viral vector: biocleavable polyrotaxane as a supramolecularly dissociative condenser for efficient intranuclear DNA release.
abstract: It has been believed that nuclear gene delivery is the most important process for gene expression, and various non-viral vectors are currently being developed with this assumption. However, some of our earlier studies revealed a surprising difference in transfection activity between viral and non-viral vectors: this difference is largely due to the result of the intranuclear disposition of DNA rather than its delivery to the nucleus (Hama S. et al. (2006), Quantitative comparison of intracellular trafficking and nuclear transcription between adenoviral and lipoplex systems. Mol. Ther., 13, 786-794). Here, we report on some direct evidence that demonstrates the importance of the release of intranuclear DNA on transfection activity. The data show that transfection activity can be substantially enhanced by integrating a multifunctional envelope-type nano device (MEND) and a biocleavable polyrotaxane (DMAE-SS-PRX) as an artificial condenser. Our integration system showed significantly higher transfection activity compared to conventional gene delivery system. Moreover, this system provides a strong support for our hypothesis that intranuclear DNA disposition plays a critical role in gene expression for non-viral vectors.
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Yamada
authors.forename: Taku
authors.initials: T
authors.lastname: Nomura
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamashita
authors.forename: Ryo
authors.initials: R
authors.lastname: Katoono
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Yui
mesh_terms: D000818:Animals; D003505:Cyclodextrins / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D005822:Genetic Vectors; D006868:Hydrolysis; D051379:Mice; D041681:NIH 3T3 Cells; D036103:Nanotechnology; D020442:Poloxamer / Q000378:metabolism*; D043862:Rotaxanes / Q000378:metabolism*; D014162:Transfection
chemical_list: D003505:Cyclodextrins; D043862:Rotaxanes; C475673:polyrotaxane; D020442:Poloxamer; D004247:DNA