期刊
GENE THERAPY
卷 12, 期 11, 页码 881-890出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.gt.3302534
关键词
nuclear import; nuclear envelope; plasmid; nuclear localization signal; nonviral gene transfer
类别
资金
- NCI NIH HHS [CA95608, R01 CA095608] Funding Source: Medline
- NHLBI NIH HHS [R01 HL059956, HL59956, P01 HL071643-020005, HL71643, P01 HL071643, R01 HL059956-07] Funding Source: Medline
Nonviral gene delivery is limited to a large extent by multiple extracellular and intracellular barriers. One of the major barriers, especially in nondividing cells, is the nuclear envelope. Once in the cytoplasm, plasmids must make their way into the nucleus in order to be expressed. Numerous studies have demonstrated that transfections work best in dividing populations of cells in which the nuclear envelope disassembles during mitosis, thus largely eliminating the barrier. However, since many of the cells that are targets for gene therapy do not actively undergo cell division during the gene transfer process, the mechanisms of nuclear transport of plasmids in nondividing cells are of critical importance. In this review, we summarize recent studies designed to elucidate the mechanisms of plasmid nuclear import in nondividing cells and discuss approaches to either exploit or circumvent these processes to increase the efficiency of gene transfer and therapy.
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