Abstract
Endocytosis is the process by which cells take up macromolecules from the surrounding medium. The best-characterized process is the so-called clathrin-dependent endocytosis, although much is also currently known about clathrin-independent endocytic processes such as those involving caveolae and lipid rafts. An understanding of endocytosis and the cellular trafficking that occurs thereafter has a great deal of relevance to current molecular medicine. Gene therapy, which is presently being investigated for its therapeutic potential in treating immunodeficiency and metabolic diseases, cancer and heart disease, employs a variety of viral and nonviral vectors, which can be delivered to the target cells of the body and are subsequently endocytosed and dissembled. A variety of vectors can be used to deliver genes to organs in vivo or cells ex vivo. Various routes of vector delivery have been investigated. The mechanisms by which vectors such as adenoviruses, adeno-associated viruses, retroviruses and liposomes enter the cell are increasingly being investigated as the effort to increase the efficiency of gene therapy continues. This review focuses on mechanisms of endocytosis and how they relate to the internal trafficking of viral and nonviral vectors in gene therapy.
Highlights
Cells are able to take up macromolecules from the surrounding medium by endocytosis
One pathway of clathrin-independent endocytosis involves the uptake of molecules in small invaginations of the plasma membrane called caveolae, which have been implicated in cell signaling and a variety of transport processes, including endocytosis [3]
The natural specificity of ligands and antibodies can be harnessed and used via their conjugation to synthetic compounds. Such specific targeting of diseased cells is crucial to the safety and efficiency of gene therapy, and remains the first of several major obstacles impeding the use of many of the currently designed vectors in a clinical setting
Summary
Cells are able to take up macromolecules from the surrounding medium by endocytosis. In this process, the material to be internalized is surrounded by an area of plasma membrane, which buds off inside the cell to form a vesicle containing the ingested material. One pathway of clathrin-independent endocytosis involves the uptake of molecules in small invaginations of the plasma membrane called caveolae, which have been implicated in cell signaling and a variety of transport processes, including endocytosis [3]. Single proteins and fluid particles can be taken up via macropinocytosis, which involves the invagination of the plasma membrane and trafficking to the endosomes These processes are more nonspecific and involve larger particles than the aforementioned clathrin- and caveolae-dependent endocytosis pathways [35]. One such GTPase, regulates the rate of clathrin-dependent endocytosis at the plasma membrane [42] and could be used as a marker for early sorting endosomes in addition or in conjunction with the transferring receptor.
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