NONVIRAL GENE-TRANSFER - APPLICATIONS IN DEVELOPMENTAL BIOLOGY AND GENE-THERAPY

The main limitation of non-viral gene transfer methods is their relati vely low efficiency in vivo. However, a number of approaches can be ta ken to improve their performances, whether the aim is studying gene fu nction during development or employing these techniques for gene thera py. Three non-viral delivery systems that we have been particularly in volved in in developing are described: the cationic lipid, dioctadecyl amidoglycylspermine (DOGS), the cationic polymer polyethylenimine (PEI ) and free DNA. The application of each of these methods to different in vivo situations is presented: the use of DOGS for transfecting embr yos and the developing mammalian nervous system; the recent applicatio n of PEI to the nervous system; and how naked DNA can be employed for transfecting different muscles and brain. The relative efficiencies ar e compared on the basis of luciferase reporter gene expression assesse d in each tissue with the most appropriate vector system. Finally, the perspectives for constructing composite vectors combining safety and efficiency are considered briefly.