Missing pieces in understanding the intracellular trafficking of polycation/DNA complexes

摘要

In about 70% of over 1400 gene therapy clinical trials that have been conducted to date worldwide, genetically-modified viruses have been the carrier of choice for delivery of therapeutic genetic material [1]. While the viruses promise both high efficiency of transfer and great protection of the therapeutic genes [2], this approach also carries a risk of causing adverse (inflammatory or immune) reactions [3,4] or even cancer [5]. Non-viral systems, such as cationic lipids and synthetic polymers (in particular, polycations), have attracted the interest of a large number of researchers as safer alternatives [6]. In particular, polycations have become popular components of non-viral gene carriers because of the relative ease with which their chemical and physical properties can be engineered for specific applications. However, the polycation-based approach has been limited in its clinical application in large part due to the poor biological activities of synthetic polymers on both cellular and systemic levels. A major issue is the difficulty associated with target-cell-specific delivery of genetic materials in vivo .