Polyethylenimine: A Versatile Cationic Polymer for Plasmid-Based Gene Delivery in the CNS

We have developed and optimized a method for delivering plasmid-based genes into the vertebrate brain. The method involves condensation of DNA into stable, small (<100 nm o), and diffusible complexes using a cationic polymer, polyethylenimine (PEI). The approach is extremely versatile as it relies on use of plasmid, not viral-based constructions. This means that construction preparation and amplification is easy to carry out, risk free, and rapidly verified. The method is extremely efficient, giving very high yields for small (nanogram)quantities of plasmid. An overriding advantage is that it provides a convenient technique for studying physiological regulation of neuronal gene function within defined brain areas at defined developmental stages or in specific physiological states. One can thus obtain data on integrated transcriptional responses that, obviously, could not be obtained by an in vitro approach without resorting to germinal transgenesis. We have applied it to the analysis of protein function and promoter regulation in the central nervous systems (CNS) of mouse, rat, and Xenopus.