title: Post-nuclear gene delivery events for transgene expression by biocleavable polyrotaxanes.
abstract: A quantitative comparison between nuclear DNA release from carriers and their transfection activity would be highly useful for improving the effectiveness of non-viral gene vectors. We previously reported that, for condensed DNA particles, a close relationship exists between the efficiency of DNA release and transfection activity, when biocleavable polyrotaxanes (DMAE-SS-PRX), in which the cationic density can be easily controlled. In this study, we first investigated the efficiencies of DNA release from condensed DNA particles with various types of DMAE-SS-PRX. The findings indicate that an optimal cationic density in DMAE-SS-PRX exists for DNA release. We then packaged condensed DNA particles in a multifunctional envelope-type nano device (MEND), and evaluated their transfection activities. The results showed that the transfection activity was increased and this increase was, to some extent, dependent on the efficiency of the DNA release. However, transfection activity decreased, when the value for the efficiency of DNA release was higher than a certain value. An investigation of the fate of intranuclear DNA indicated that a very high efficiency of DNA release has a positive influence on transcription, however, it would inhibit the post-transcription process; nuclear mRNA export, translation and related processes. Such information provides a new viewpoint for the development of cationic polymer-based vectors.
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Hokkaido University, Kita-12, Nishi-6, Kita-ku, 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: Nobuhiko
authors.initials: N
authors.lastname: Yui
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D015870:Gene Expression; D018014:Gene Transfer Techniques; D053758:Nanoparticles; D010957:Plasmids / Q000378:metabolism; D043862:Rotaxanes / Q000737:chemistry*; D014158:Transcription, Genetic; D014162:Transfection; D019076:Transgenes / Q000235:genetics*
chemical_list: D043862:Rotaxanes; D004247:DNA