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      Uptake pathways and subsequent intracellular trafficking in nonviral gene delivery.

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          Abstract

          The successful delivery of therapeutic genes to the designated target cells and their availability at the intracellular site of action are crucial requirements for successful gene therapy. Nonviral gene delivery is currently a subject of increasing attention because of its relative safety and simplicity of use; however, its use is still far from being ideal because of its comparatively low efficiency. Most of the currently available nonviral gene vectors rely on two main components, cationic lipids and cationic polymers, and a variety of functional devices can be added to further optimize the systems. The design of these functional devices depends mainly on our understanding of the mechanisms involved in the cellular uptake and intracellular disposition of the therapeutic genes as well as their carriers. Macromolecules are internalized into cells by a variety of mechanisms, and their intracellular fate is usually linked to the entry mechanism. Therefore, the successful design of a nonviral gene delivery system requires a deep understanding of gene/carrier interactions as well as the mechanisms involved in the interaction of the systems with the target cells. In this article, we review the different uptake pathways that are involved in nonviral gene delivery from a gene delivery point of view. In addition, available knowledge concerning cellular entry and the intracellular trafficking of cationic lipid-DNA complexes (lipoplexes) and cationic polymer-DNA complexes (polyplexes) is summarized.

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          Author and article information

          Journal
          Pharmacol Rev
          Pharmacological reviews
          American Society for Pharmacology & Experimental Therapeutics (ASPET)
          0031-6997
          0031-6997
          Mar 2006
          : 58
          : 1
          Affiliations
          [1 ] Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
          Article
          58/1/32
          10.1124/pr.58.1.8
          16507881
          01f761fe-3ff9-47f3-a907-6675a7d62fce
          History

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