Kidney-selective gene transfection using anionic bubble lipopolyplexes with renal ultrasound irradiation in mice

Abstract

This study assessed the ability of a new ultrasound (US) responsive gene delivery carrier, bubble lipopolyplexes, to deliver genes to the kidneys. The bubble lipopolyplexes showed highly selective gene expression in kidney tubules, but only after renal irradiation with US. These bubble lipopolyplexes, however, did not increase the expression of biomarkers of kidney injury, including blood urea nitrogen, serum creatinine, kidney injury molecule-1 mRNA, and clusterin mRNA, or induce any histopathological abnormalities in the kidney. Furthermore, pDNA containing CMV early enhancer/chicken beta-actin promoter prolonged gene expression by the bubble lipopolyplexes in the kidney for 42 days. This novel renal gene delivery method, in which transfection of bubble lipopolyplexes was followed by US irradiation of the kidneys, resulting in cell-selective, high, and long-term gene expression without renal injury in mice, may have future applications in patient treatment.

From the clinical editor: This study demonstrates a novel gene delivery method to the kidneys, utilizing bubble resulting in highly selective gene expression in renal tubules after ultrasound irradiation. In the studied rodent model, there was no evidence for renal damage using this novel delivery system.

Keywords: Gene delivery; Kidney; Liposomes; Sonoporation.