Kidney-specific Sonoporation-mediated Gene Transfer

Mol Ther. 2016 Feb;24(1):125-34. doi: 10.1038/mt.2015.171. Epub 2015 Sep 30.

Abstract

Sonoporation can deliver agents to target local organs by systemic administration, while decreasing the associated risk of adverse effects. Sonoporation has been used for a variety of materials and in a variety of organs. Herein, we demonstrated that local sonoporation to the kidney can offer highly efficient transfer of oligonucleotides, which were systemically administrated to the tubular epithelium with high specificity. Ultrasonic wave irradiation to the kidney collapsed the microbubbles and transiently affected the glomerular filtration barrier and increased glomerular permeability. Oligonucleotides were passed through the barrier all at once and were absorbed throughout the tubular epithelium. Tumor necrosis factor alpha (TNFα), which plays a central role in renal ischemia-reperfusion injury, was targeted using small interfering RNA (siRNA) with renal sonoporation in a murine model. The reduction of TNFα expression after single gene transfer significantly inhibited the expression of kidney injury markers, suggesting that systemic administration of siRNA under temporary and local sonoporation could be applicable in the clinical setting of ischemic acute kidney injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Electroporation / methods*
  • Gene Expression Regulation
  • Gene Transfer Techniques
  • Genetic Therapy / methods
  • Humans
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / etiology
  • Kidney Diseases / metabolism
  • Kidney Diseases / therapy*
  • Mice
  • NIH 3T3 Cells
  • Organ Specificity
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / pharmacology
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / therapy*
  • Sonication / methods*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • RNA, Small Interfering
  • Tumor Necrosis Factor-alpha