title: Emerging significance of plasmid DNA nuclear import in gene therapy.
abstract: The signal-mediated import of plasmid DNA (pDNA) into nondividing mammalian cell nuclei is one of the key biological obstacles to nonviral therapeutic pDNA delivery. Overcoming this barrier to pDNA transfer is thus an important fundamental objective in gene therapy. Here, we outline the rationale behind current and future strategies for signal-mediated pDNA nuclear import. Results obtained from studies of the nuclear delivery of pDNA coupled to experimentally defined nuclear localisation signal (NLS) peptides, in conjunction with detergent-permeabilised reconstitution cell assays, direct intracellular microinjection, cell-based transfection, and a limited number of in vivo experiments are discussed.
authors.affiliation: Department of Gene Therapy, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK. f.munkonge@imperial.ac.uk
authors.forename: Felix M
authors.initials: FM
authors.lastname: Munkonge
authors.forename: David A
authors.initials: DA
authors.lastname: Dean
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hillery
authors.forename: Uta
authors.initials: U
authors.lastname: Griesenbach
authors.forename: Eric W F W
authors.initials: EW
authors.lastname: Alton
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D010957:Plasmids / Q000235:genetics* / Q000378:metabolism*