Journal
CURRENT GENE THERAPY
Volume 6, Issue 6, Pages 671-681Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/156652306779010688
Keywords
transfection; plasmid; microtubules; nuclear pore complex; nuclear localization signal; nuclear transport; actin; cytoskeleton
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Funding
- NHLBI NIH HHS [HL81148, R01 HL059956, P01 HL071643, P01 HL071643-040005, R01 HL081148, R01 HL081148-02, HL71643] Funding Source: Medline
- PHS HHS [JL59956] Funding Source: Medline
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Under physiologically relevant conditions, the levels of non-viral gene transfer are low at best. The reason for this is that many barriers exist for the efficient transfer of genes to cells, even before any gene expression can occur. While many transfection strategies focus on DNA condensation and overcoming the plasma membrane, events associated with the intracellular trafficking of the DNA complexes have not been as extensively studied. Once internalized, plasmids must travel potentially long distances through the cytoplasm to reach their next barrier, the nuclear envelope. This review summarizes the current progress on the cytoplasmic trafficking and nuclear transport of plasmids used for gene therapy applications. Both of these processes utilize specific and defined mechanisms to facilitate movement of DNA complexes through the cell. The continued elucidation and exploitation of these mechanisms will lead to improved strategies for transfection and successful gene therapy.
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