Plasmid DNA Gene Therapy by Electroporation: Principles and Recent Advances

Abstract

Simple plasmid DNA injection is a safe and feasible gene transfer method, but it confers low transfection efficiency and transgene expression. This non-viral gene transfer method is enhanced by physical delivery methods, such as electroporation and the use of a gene gun. In vivo electroporation has been rapidly developed over the last two decades to deliver DNA to various tissues or organs. It is generally considered that membrane permeabilization and DNA electrophoresis play important roles in electro-gene transfer. Skeletal muscle is a well characterized target tissue for electroporation, because it is accessible and allows for long-lasting gene expression ( > one year). Skin is also a target tissue because of its accessibility and immunogenicity. Numerous studies have been performed using in vivo electroporation in animal models of disease. Clinical trials of DNA vaccines and immunotherapy for cancer treatment using in vivo electroporation have been initiated in patients with melanoma and prostate cancer. Furthermore, electroporation has been applied to DNA vaccines for infectious diseases to enhance immunogenicity, and the relevant clinical trials have been initiated. The gene gun approach is also being applied for the delivery of DNA vaccines against infectious diseases to the skin. Here, we review recent advances in the mechanism of in vivo electroporation, and summarize the findings of recent preclinical and clinical studies using this technology.

Silica and ORMOSIL nanoparticles for gene delivery

“…Non-viral methods typically produce low levels of transfection and expression of the gene, however, when compared with viral methods. Nevertheless, some recent developments in vector technology have yielded molecules and techniques with efficiencies that approach those of viruses [40].…”

Phoenix rising: gene therapy makes a comeback

“…Although beyond the scope of this review, numerous other viruses are being developed as gene transfer tools, including, but not limited to, vaccinia virus [101], human parainfluenza virus [102,103], human respiratory syncytial virus [104], alphavirus [105], and herpes simplex virus [106], as well as physical (e.g. electroporation [107] and magnetofection [108]) and chemical (e.g. lipoplexes [108]) methods, including RNA nanotechnology [109], to improve vector (or DNA) delivery.…”

Emerging biotechnological strategies for non-viral antiangiogenic gene therapy

“…Through this method, DNA can achieve long-lasting expression much greater than naked DNA injection. So far, clinical trials of naked DNA for cancer treatment using in vivo electroporation have been initiated in patients with melanoma and prostate cancer ( Table 2) [38]. However, up to now, skeletal muscle still is the most promising administration site for electroporation [39], because it has been reported that the ability of plasmid DNA to transfect other cells such as ocular/ retinal cells are negative with little-to-no transfection or gene expression [40,41].…”