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

• Main Authors: Natsuko Oyama, Haruyuki Takahashi, Maho Kawaguchi, Hirotaka Miyamoto, Koyo Nishida, Masako Tsurumaru, Mikiro Nakashima, Fumiyoshi Yamashita, Mitsuru Hashida, Shigeru Kawakami
• Format: Article
• Language: English
• Published: MDPI AG 2020-02-01
• Series: Pharmaceutics
• Subjects: naked pdna; physical methods; pressure; gene transfection; kidney; local administration; renal artery; renal ureter
• Online Access: https://www.mdpi.com/1999-4923/12/2/114

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.