Figure 1

The endocytic pathway in gene therapy. Gene therapy vectors enter the cells via membrane structures that allow endocytosis to occur, such as clathrin-coated pits, caveolae and lipid rafts. Clathrin-coated pits are lined by clathrin, caveolae are lined by caveolin and lipid rafts are cell membrane domains that contain cholesterol, glycosphinogolipids and possibly the protein flotillin. Each structure invaginates to form a vesicle and, subsequently, an early endosome. The early endosome sorts the endocytosed material into material that will be recycled back to the plasma membrane, material that will be secreted and material that will be degraded by fusion with the lysosome in later steps. Some viruses and proteins can escape lysosomal degradation via a decrease in the pH of the endosome. These particles/molecules can then be trafficked into the nucleus, where they can act to silence or activate various genes. GSL, glycosphingolipids.