ENDOCYTOSIS: A PROMISING APPROACH FOR GENE TRANSFER TECHNOLOGY pp. 203-209
Authors: Chiaki Hidai, Division of Physiology, Department of Biomedical Science, Nihon University School of Medicine, Tokyo, Japan
Abstract: Recently, a number of new methods for gene transfer have been put forward to advance biomedical study and gene therapy. Although viral vectors confer high efficiency of gene transfer, they also have the added risk of carcinogenesis, such as via random genomic integration. Although non-viral vectors lack this risk, they also tended to be less efficient for gene transfer. Thus, various efforts are being made to improve gene transfer techniques based on non-viral vectors. For example, novel chemical transfection reagents have been developed, including those with improved extracellular binding, engulfment, and utilization of the introduced nucleic acids. Additionally, receptor-mediated endocytosis has been used to create vectors using chemicals, growth factor peptides, extracellular matrix proteins, and viral proteins. This method enables selection of target cells and increased gene transfer efficiency as compared with other non-viral methods. In reviewing reports of these efforts, we have found that in terms of efficiency, differences among cells are a bigger factor than differences among transfection reagents. Some cells are always more easily transfected than others. The biological state of a given cell type, such as which endocytic pathways are functional in the cell prior to treatment, may be an important factor in endocytosis-mediated gene transfer. Therefore, studying how endocytosis is regulated should provide useful insights into how to improve gene transfer technology. Endocytosis can be initiated by the binding of ligands to their receptors on the surface of the cell membrane, followed by internalization. To make best use of this endogenous function for introduction of exogenous molecules, it will be necessary to gain a better understanding of what types of molecules efficiently induce initiation of endocytosis. In this commentary, we summarize the current state-of-the-art in non-viral gene transfer and supporting technologies related to the initiation of endocytosis. We will also discuss specific ways in which what is known about endocytosis might be exploited in order to facilitate development of new and improved non-viral methods for gene transfer.
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