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Efficient Messenger RNA Delivery to the Kidney Using Renal Pelvis Injection in Mice.
Oyama, Natsuko; Kawaguchi, Maho; Itaka, Keiji; Kawakami, Shigeru.
  • Oyama N; Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
  • Kawaguchi M; Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
  • Itaka K; Department of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kanda-Surugadai, Tokyo 101-0062, Japan.
  • Kawakami S; Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan.
Pharmaceutics ; 13(11)2021 Oct 29.
Article in English | MEDLINE | ID: covidwho-1534228
ABSTRACT
Renal dysfunction is often associated with the inflammatory cascade, leading to non-reversible nephrofibrosis. Gene therapy has the ability to treat the pathology. However, the difficulty in introducing genes into the kidney, via either viral vectors or plasmid DNA (pDNA), has hampered its extensive clinical use. Messenger RNA (mRNA) therapeutics has recently attracted attention as alternative gene therapies. mRNA allows protein production into post-mitotic cells without the need for transport to the nuclei in the target cells. However, few studies have reported the delivery of mRNA to the kidney. In this study, we attempted to deliver mRNA to the kidney based on the principle of pressure stimulation, by administering mRNA-loaded polyplex nanomicelles via a renal pelvis injection, directly into the kidney. Compared with the administration of naked plasmid DNA (pDNA) and naked mRNA, the mRNA-loaded nanomicelles diffusely induced protein expression in a greater number of cells at the tubular epithelium for some days. The plasma creatinine (Cre) and blood urea nitrogen (BUN) levels after the administration remained similar to those of the sham-operated controls, without marked changes in histological sections. The safety and efficacy of mRNA-loaded nanomicelles would make distinct contributions to the development of mRNA therapeutics for the kidney.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Year: 2021 Document Type: Article Affiliation country: Pharmaceutics13111810

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Full text: Available Collection: International databases Database: MEDLINE Language: English Year: 2021 Document Type: Article Affiliation country: Pharmaceutics13111810