Efficient Messenger RNA Delivery to the Kidney Using Renal Pelvis Injection in Mice
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...
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| Format: | Article |
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MDPI AG
2021-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/11/1810 |
| _version_ | 1797508836844634112 |
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| author | Natsuko Oyama Maho Kawaguchi Keiji Itaka Shigeru Kawakami |
| author_facet | Natsuko Oyama Maho Kawaguchi Keiji Itaka Shigeru Kawakami |
| author_sort | Natsuko Oyama |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T05:09:32Z |
| format | Article |
| id | doaj.art-fcae87e9a1ee4988aeb9d5cb3859540f |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T05:09:32Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-fcae87e9a1ee4988aeb9d5cb3859540f2023-11-23T00:57:58ZengMDPI AGPharmaceutics1999-49232021-10-011311181010.3390/pharmaceutics13111810Efficient Messenger RNA Delivery to the Kidney Using Renal Pelvis Injection in MiceNatsuko Oyama0Maho Kawaguchi1Keiji Itaka2Shigeru Kawakami3Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, JapanDepartment of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, JapanDepartment of Biofunction Research, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kanda-Surugadai, Tokyo 101-0062, JapanDepartment of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, JapanRenal 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.https://www.mdpi.com/1999-4923/13/11/1810messenger RNA (mRNA)mRNA therapeuticspolyplex nanomicellekidneyrenal pelvis injectionhydrodynamic injection |
| spellingShingle | Natsuko Oyama Maho Kawaguchi Keiji Itaka Shigeru Kawakami Efficient Messenger RNA Delivery to the Kidney Using Renal Pelvis Injection in Mice Pharmaceutics messenger RNA (mRNA) mRNA therapeutics polyplex nanomicelle kidney renal pelvis injection hydrodynamic injection |
| title | Efficient Messenger RNA Delivery to the Kidney Using Renal Pelvis Injection in Mice |
| title_full | Efficient Messenger RNA Delivery to the Kidney Using Renal Pelvis Injection in Mice |
| title_fullStr | Efficient Messenger RNA Delivery to the Kidney Using Renal Pelvis Injection in Mice |
| title_full_unstemmed | Efficient Messenger RNA Delivery to the Kidney Using Renal Pelvis Injection in Mice |
| title_short | Efficient Messenger RNA Delivery to the Kidney Using Renal Pelvis Injection in Mice |
| title_sort | efficient messenger rna delivery to the kidney using renal pelvis injection in mice |
| topic | messenger RNA (mRNA) mRNA therapeutics polyplex nanomicelle kidney renal pelvis injection hydrodynamic injection |
| url | https://www.mdpi.com/1999-4923/13/11/1810 |
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