Electroporation‐mediated <i>ex vivo</i> gene transfer into graft not requiring injection pressure in orthotopic liver transplantation

Kobayashi, Shogo; Dono, Keizo; Takahara, Shiro; Isaka, Yoshitaka; Imai, Enyu; Lu, Zhenhui; Nagano, Hiroaki; Kato, Tomoaki; Umeshita, Koji; Nakamori, Shoji; Sakon, Masato; Monden, Morito

doi:10.1002/jgm.370

Cited by 6 publications

(2 citation statements)

References 24 publications

(40 reference statements)

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“…For liposome and polymer-mediated delivery, intravascular injection is a simple and highly effective way to target the vascular endothelium, with the majority of gene transfer occurring in regions where the complexes get stuck due to reduced vessel diameter (e.g., the lung microvasculature). Alternatively, by injecting defined vessels that feed only one organ, transfer of DNA to that organ such as the kidney or liver or its proximal vasculature can also be achieved (Kobayashi et al, 2003; Tsujie, Isaka, Nakamura, Imai, & Hori, 2001). However, due to rapid flow rates, intravascular injection of DNA followed by electroporation has not been able to be used as a means to transfect vascular tissue, other than that in the liver or tumors (in this case, the electrodes are placed on the liver following intravascular injection of DNA) (Jaichandran et al, 2006).…”

Section: Electroporation Of the Cardiovascular Systemmentioning

confidence: 99%

Electroporation-Mediated Gene Delivery

Young

Dean

2015

Advances in Genetics

136

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Electroporation has been used extensively to transfer DNA to bacteria, yeast, and mammalian cells in culture for the past 30 years. Over this time, numerous advances have been made, from using fields to facilitate cell fusion, delivery of chemotherapeutic drugs to cells and tissues, and most importantly, gene and drug delivery in living tissues from rodents to man. Electroporation uses electrical fields to transiently destabilize the membrane allowing the entry of normally impermeable macromolecules into the cytoplasm. Surprisingly, at the appropriate field strengths, the application of these fields to tissues results in little, if any, damage or trauma. Indeed, electroporation has even been used successfully in human trials for gene delivery for the treatment of tumors and for vaccine development. Electroporation can lead to between 100 and 1000-fold increases in gene delivery and expression and can also increase both the distribution of cells taking up and expressing the DNA as well as the absolute amount of gene product per cell (likely due to increased delivery of plasmids into each cell). Effective electroporation depends on electric field parameters, electrode design, the tissues and cells being targeted, and the plasmids that are being transferred themselves. Most importantly, there is no single combination of these variables that leads to greatest efficacy in every situation; optimization is required in every new setting. Electroporation-mediated in vivo gene delivery has proven highly effective in vaccine production, transgene expression, enzyme replacement, and control of a variety of cancers. Almost any tissue can be targeted with electroporation, including muscle, skin, heart, liver, lung, and vasculature. This chapter will provide an overview of the theory of electroporation for the delivery of DNA both in individual cells and in tissues and its application for in vivo gene delivery in a number of animal models.

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Section: Electroporation Of the Cardiovascular Systemmentioning

confidence: 99%

Electroporation-Mediated Gene Delivery

Young

Dean

2015

Advances in Genetics

136

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“…Similarly, tail vein injection of DNA-liposome complexes results in high level expression in the hepatic and pulmonary endothelium (Uyechi et al, 2001). The use of the vasculature to target DNA to an organ has also been combined with electroporation to target several tissues, including the kidney and liver (Tsujie et al, 2001;Kobayashi et al, 2003). In all cases, DNA is delivered by injection into the vessels feeding the target organ: the renal artery in the case of the kidney and the portal vein for the liver.…”

Section: Electroporation Of Downstream Target Organs Following Luminamentioning

confidence: 99%

Electroporation of the Vasculature and the Lung

Dean

2003

DNA and Cell Biology

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Electroporation has proven to be a highly effective technique for the in vivo delivery of genes to a number of solid tissues. In most of the reported methods, DNA is injected into the target tissue and electrodes are placed directly on or in the tissue for application of the electric field. While this works well for solid tissues, there are many tissues and organs that are not amenable to such an approach. In this review I will focus on the development of electroporation protocols for two such tissues: the vasculature and the lung. Several methods for in vivo electroporation of the vasculature have been developed in recent years that deliver DNA to vessel segments from either the inside or outside of the vessel. The advantages and disadvantages of each are discussed, as are the applications for which they have been used. In more recent work, our laboratory has developed a novel method to deliver genes to the rodent lung that results in high level, uniform, gene expression throughout all cell types of the lung. Most importantly, this technique is safe, and causes no inflammatory response or alterations in normal physiology of the organs. Taken together, these studies demonstrate the utility of electroporation for gene transfer to noninjectible tissues.

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