Gene Delivery Using Physical Methods - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 93

Hydrodynamic gene delivery combines naked DNA and hydrodynamic pressure gen-
erated using rapid injection of a large volume of fluid into a blood vessel, to deliver
genetic materials into parenchyma cells. Hydrodynamic delivery began in the late
1990s with investigations into intravascular injection of plasmid DNA solution for
gene delivery in whole animals by application of controlled hydrodynamic pressure
in capillaries, to enhance endothelial and parenchymal cell permeability for enhanced
transgene expression [26,68,69] .
The initial investigations by Budker et al. [26] , �iu et al. [68] , and Zhang et al.
[69] have shown successful systemic gene transfer in skeletal muscles and other
organs in rats by intravascular gene transfer with higher volume and pressure, which
lead to future investigations in this method. The hydrodynamic method was found
to be superior to the existing delivery systems because of its simplicity, efficiency,
and versatility. It has been currently applied to delivery of DNA, RNA, proteins,
and synthetic compounds into the cells in various tissues of small animals, and has
inspired recent attempts at establishing a hydrodynamic procedure for clinical use
[70] . The hydrodynamic method has been most widely used for gene delivery to the
liver [68,69] , kidneys, and muscle tissues [68,71] . Gene expression in hydrodynami-
cally transfected animals was found to be long lasting [68,69,71-73] and may show
therapeutic levels and efficacy [74-77] . However, it suffers from the disadvantage of
possibly boosting blood pressure and reducing heart rate, due to enhanced volume of
the system, and possibly leads to death.
The concept of hydrodynamic gene delivery has been used widely due to better
knowledge of the construction and properties of blood vessels and the fluid circu-
lating through them. This delivery system finds parenchyma cells as the main tar-
get because parenchyma cells are directly associated with capillary endothelial cells,
allowing immediate access of DNA to parenchyma cells once the endothelial barrier
is disrupted. In addition, the capillary wall is thin, stretchable, and relatively easy to
break. The high pressure produced during the injection of a high volume of DNA
solution into the blood vessels is the driving force for hydrodynamic gene delivery,
by increasing the capillary endothelial permeability through enlargement of fenestra-
tions and creating pores in the adjacent parenchymal cell plasma membrane, which
provides the path for DNA to enter into the cell [74-76] . Shortly after injection, the
membrane pores lock, and the injected DNA molecules are entrapped inside the cell.
The applied hydrodynamic force, the structure of capillaries (fenestrated or continu-
ous), and the structure of cells adjacent to the capillary are key factors deciding the
success of hydrodynamic gene delivery [71,77-79] .
The original procedure of hydrodynamic gene delivery was established based on
rich experimental results associated with liver gene transfer. Numerous investigators
have developed significant modifications to adapt the procedure for other gene deliv-
ery applications [80-86] . In a decade, this technique has gained wide acceptance
as a tool for gene therapy studies, and extensive research geared toward improving
hydrodynamic delivery for broader applications is now being conducted in many
laboratories.
Various advances have been made in the hydrodynamic delivery method to achieve
the desired gene transfection in different tissues and animals. Table 3.2 presents a brief