Polyethylenimine Derivatives as Potent Nonviral Vectors for Gene Transfer

Abstract

The delivery of a functional gene into a tissue can allow the correction of gene defaults or mutations such as those observed in severe hereditary pathologies or in cancer tissues and could lead to gene therapy. To achieve gene transfer, viral vectors are mainly used because of their intrinsic ability to enter the cells and promote expression of the transgene. However, many factors can limit the use of viral vectors, including a heavy laboratory infrastructure, and, in the case of iterative administration, the induction of immune response against viral proteins. Alternative gene transfer technologies based on nonviral vectors have been proposed. Polyethylenimine (PEI) derivatives are polycationic molecules that are able to form stable complexes with plasmidic DNA. PEI/DNA complexes attach to the cell surface, migrate into clumps that enter the cell by endocytosis and are deagregated in an acidic lysosomal compartment and/or enter the nucleus. PEI derivatives can be proposed as linear (22 kDa) or reticulated (25 kDa) molecules that prove efficient for gene transfer in vitro and in vivo. Besides extensive applications of unsubstituted PEI, glycosylated-PEI derivatives were proposed and reported to enhance gene transfer efficiency through decreased size and aggregation of PEI/DNA complexes. Galactosylated-PEI derivatives have been reported to enhance interactions with cell membranes through carbohydrate-binding protein recognition and specifically target PEI/DNA complexes toward biological systems that express galectins. More recently, glucosylated PEI derivatives have been shown to yield higher and longer-lasting transgene expression than unsubstituted-PEI in human head and neck carcinoma tumor cells. In the present paper, a review of in vitro and in vivo properties of PEI-mediated gene transfer experiments is presented. (c) 2002 Prous Science. All rights reserved.