Injection of DNA Using High-Pressure Jets (Jet Injection)

Introduction of Jet Injection

The jet injection is a physical delivery method that uses high pressure to force microdroplets of liquid to penetrates the skin to deliver a drug or vaccine into intradermal, subcutaneous, or intramuscular tissues. The jet injection method is used to inject the molecules (such as drugs, nucleic acids) diluted in liquid without the use of a needle or particles. This high-pressure liquid stream is used to pierce the skin or target tissue, with the pressure reaching up to 3-4 bar and the velocity of the droplets ranging from 100 ms^-1 to 200 ms^-1. The benefit of using jet injection is to minimize patient discomfort.

The jet injection methods have been widely used in DNA vaccination studies to induce the host's immune response to the gene product encoded and expressed by the plasmid used. Of these studies, most have targeted muscle or epidermis as a target for gene transfer, while only a few studies are aimed at the direct in vivo gene transfer into tumor tissue.

Figure 1. Schematic representation of jet injection pattern in the tumor tissue. (Walther, 2001)

Mechanisms of Jet Injection

Although jet injection has been commercially used for vaccinations since the 1940s, little is known about the mechanism of jet injection or the parameters that control it. The physical phenomenon related to jet-induced penetration in the skin has been investigated only recently. In jet injection, the high pressure of the jet creates a hole in the skin surface, which is most likely caused by skin corrosion or fracture. The depth of this hole is increased until the liquid accumulated in the hole is sufficient to slow the speed of the incoming jet, and then stop moving forward. The penetration of the injected molecules inside the cells is a result of the pressure caused by the liquid locally delivered into the targeted tissue. The efficiency and penetration depth of this method depends on several jet parameters, including the nozzle diameter (typically in the range of 150-300 µm), the speed of the liquid jet, and the distance between the nozzle and the skin surface.

Application of Jet Injection

• Jet injection in clinical applications

Since 1930, various types of jet injectors have been developed and used in clinical applications. They have been used to deliver a variety of macromolecules, including vaccines, insulin and growth hormones in a large number of patients and erythropoietin and interferon in a few cases. Perhaps the most important use is in the WHO vaccination campaign against smallpox. The feasibility of 600 or more subcutaneous injections per hour makes it the fastest immunization system. In addition, jet injectors have also been used to deliver numerous small molecules such as lidocaine, steroids, anesthetics, penicillin midazolam and ketamine. Anesthetics, such as lidocaine, have been commonly delivered using jet injections for various applications including dental procedures, dermal surgical procedures and peripheral intravenous cannula insertion.

• Jet injection in gene therapy

The jet injection can be also used in gene therapy for the transfer of genes to many tissues such as skin, fat, muscle and mammary cells of mice and sheep. In mice, injections of naked DNA encoding the cytosine deaminase suicide gene using the jet injection method can promote tumor regression caused by the injection of 5-fluorocytosine.

• Other applications

Another attractive application is jet-mediated gene delivery for the treatment of skin diseases caused by genetic defects, such as the production of abnormal proteins in keratinocytes. DNA-encoded shRNA, utilized to reverse the classical MDR1/P-glycoprotein-mediated multidrug resistance phenotype in vivo, is also delivered by the jet injection method in mice.

Reference

1. Walther, W.; et al. (2001). Non-viral in vivo gene delivery into tumors using a novel low volume jet-injection technology. Gene therapy. 8(3): 173.