title: Kidney-specific Sonoporation-mediated Gene Transfer.
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.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Graduate School of Medical Science Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Ishida
authors.affiliation: Department of Regenerative Medicine, Graduate School of Medical Science Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kami
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Graduate School of Medical Science Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kusaba
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Graduate School of Medical Science Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Kirita
authors.affiliation: Department of Immunology, Graduate School of Medical Science Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tsunao
authors.initials: T
authors.lastname: Kishida
authors.affiliation: Department of Immunology, Graduate School of Medical Science Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Osam
authors.initials: O
authors.lastname: Mazda
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Graduate School of Medical Science Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Takaomi
authors.initials: T
authors.lastname: Adachi
authors.affiliation: Department of Regenerative Medicine, Graduate School of Medical Science Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Gojo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018274:Electroporation / Q000379:methods*; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D041681:NIH 3T3 Cells; D009928:Organ Specificity; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism / Q000628:therapy*; D013010:Sonication / Q000379:methods*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha