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

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.

Development of a DNA Vaccine for Melanoma Metastasis by Inhalation Based on an Analysis of Transgene Expression Characteristics of Naked pDNA and a Ternary Complex in Mouse Lung Tissues

“…Although the intrapulmonary distribution of gene expression after inhalation is important information for therapeutic applications, it has not yet been elucidated in detail. Our group developed a multicolor deep imaging system using a tissue-clearing method and confocal microscopy in several organs [18][19][20][21]. We herein applied the tissue-clearing method to evaluate the intrapulmonary distribution of transgene expression using a multicolor deep imaging system for the first time.…”

Advances in the Development and the Applications of Nonviral, Episomal Vectors for Gene Therapy

“…The S/MARs are placed between the bacterial and mammalian transcription units. Current publications suggest the vector is safe and can promote effective therapeutic gene transfer 63,64 . Other recent work with CpG-free vectors based on this vector has proposed that the position of S/MAR in the 3'UTR of mRNA may not always be ideal in the case of secreted proteins.…”

“…Current publications suggest the vector is safe and can promote effective therapeutic gene transfer. 63 , 64 …”

Efficient Messenger RNA Delivery to the Kidney Using Renal Pelvis Injection in Mice

“…However, these injections caused transient renal damage, as indicated by the elevation in blood urea nitrogen (BUN) level a few days after the injection, as well as the formation of a small hematoma under the kidney capsule and within the kidney parenchyma [11,12]. Recently, we also investigated hydrodynamic pDNA injection into the kidney via several local approaches from the renal infundibulum, renal artery, and renal pelvis [13]. To minimize tissue damage, we evaluated the effect of a reduced injection volume of 10 µL/mouse, together with the alteration of injection speed.…”