Plasmid-based gene delivery to target tissues in vivo: the intravascular approach.

Over the past several years, significant progress has been made in the development of non-viral methodologies that can effectively deliver genes to target tissues in vivo. One of the most surprising successes has been the discovery that naked plasmid DNA (pDNA) can be delivered into tissues such as liver and muscle with high efficiency using the vascular system. The key breakthrough involved the realization that pDNA could be injected rapidly into blood vessels (using increased volumes) in a manner that facilitates extravasation of the DNA solution outside the blood vessel wall. The extravasation process places the DNA in contact with the plasma membranes of the underlying parenchymal cells of the target organ. This intravascular delivery technique, termed 'hydrodynamic delivery', has become established as the primary non-viral methodology for delivering pDNA expression constructs to target tissues in vivo. This review highlights many of the most recent studies in which increased volume/rapid injection procedures have been used. These include studies in which the technology was used as a new and powerful tool to address in vivo gene expression questions, as well as numerous studies that were designed to better understand or improve the methodology. It is these scientific efforts that have served to fuel the development of this delivery technology from simply an interesting phenomenon to a highly useful and broadly used gene delivery methodology.