Effects of Tissue Pressure on Transgene Expression Characteristics via Renal Local Administration Routes from Ureter or Renal Artery in the Rat Kidney

Natsuko Oyama,Hirotaka Miyamoto,Masako Tsurumaru,Maho Kawaguchi,Mitsuru Hashida,Shigeru Kawakami,Haruyuki Takahashi,Mikiro Nakashima,Fumiyoshi Yamashita,Koyo Nishida

doi:10.3390/pharmaceutics12020114

Natsuko Oyama, Hirotaka Miyamoto + Show 8 more

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https://doi.org/10.3390/pharmaceutics12020114

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Journal: Pharmaceutics	Publication Date: Feb 1, 2020
Citations: 7	License type: CC BY 4.0

Affiliation: Nagasaki University, Kyoto University

Abstract

We previously developed a renal pressure-mediated transfection method (renal pressure method) as a kidney-specific in vivo gene delivery system. However, additional information on selecting other injection routes and applicable animals remains unclear. In this study, we selected renal arterial and ureteral injections as local administration routes and evaluated the characteristics of gene delivery such as efficacy, safety, and distribution in pressured kidney of rat. Immediately after the naked pDNA injection, via renal artery or ureter, the left kidney of the rat was pressured using a pressure controlling device. Transfection efficiency of the pressured kidney was about 100-fold higher than that of the injection only group in both administration routes. The optimal pressure intensity in the rat kidney was 1.2 N/cm2 for renal arterial injection and 0.9 N/cm2 for ureteral injection. We found that transgene expression site differs according to administration route: cortical fibroblasts and renal tubule in renal arterial injection and cortical and medullary tubule and medullary collecting duct in ureteral injection. This is the first report to demonstrate that the renal pressure method can also be effective, after renal arterial and ureteral injections, in rat kidney.

Highlights

IntroductionNaked plasmid DNA (pDNA) transfer is simple and less immunogenic, compared with other viral or non-viral vectors; but intravenous injection of naked pDNA shows low transfection efficiency [1]
Gene therapy is a potential approach for various incurable diseases
As the other injection route, several groups have reported that retrograde injection from ureter or renal pelvis is a promising route to target cortical and medullary renal tubules, using viral and non-viral vectors [1,15,17,29]. To confirm whether it is possible in combination with renal pressure, we evaluated distribution of transgene expression and fluorescent-labeled plasmid DNA (pDNA), using the renal pressure method, after ureteral injection

Summary

Introduction

Naked plasmid DNA (pDNA) transfer is simple and less immunogenic, compared with other viral or non-viral vectors; but intravenous injection of naked pDNA shows low transfection efficiency [1]. We previously developed a renal pressure-mediated transfection (renal pressure method) [6,7] and suction-mediated transfection (renal suction method) methods [8,9] in mice. In these methods, direct pressure or suction after intravenous naked pDNA injection can achieve kidney-specific gene transfer without causing marked renal dysfunction in mice [6,7,8,9]. The direction of pressure stimulation is different between the renal pressure and suction methods, both methods induce tissue deformation [9,10]

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