Emerging significance of plasmid DNA nuclear import in gene therapy

被引:64
作者
Munkonge, FM [1 ]
Dean, DA
Hillery, E
Griesenbach, U
Alton, EWFW
机构
[1] Univ London Imperial Coll Sci Technol & Med, Dept Gene Therapy, Natl Heart & Lung Inst, London, England
[2] UK Cyst Fibrosis Gene Therapy Consortium, London, England
[3] Northwestern Univ, Div Pulm & Crit Care Med, Chicago, IL 60611 USA
关键词
plasmid DNA (pDNA); nuclear import; cyto-nucleoplasmic transport; gene therapy; nonviral gene transfer; nuclear localising signals; peptide nucleic acid (PNA); nuclear localising signals (NLS);
D O I
10.1016/S0169-409X(03)00050-4
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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. (C) 2003 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:749 / 760
页数:12
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