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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Autores principales:	Natsuko Oyama, Maho Kawaguchi, Keiji Itaka, Shigeru Kawakami
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	messenger RNA (mRNA) mRNA therapeutics polyplex nanomicelle kidney renal pelvis injection hydrodynamic injection Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/fcae87e9a1ee4988aeb9d5cb3859540f
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spelling	oai:doaj.org-article:fcae87e9a1ee4988aeb9d5cb3859540f2021-11-25T18:40:51ZEfficient Messenger RNA Delivery to the Kidney Using Renal Pelvis Injection in Mice10.3390/pharmaceutics131118101999-4923https://doaj.org/article/fcae87e9a1ee4988aeb9d5cb3859540f2021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1810https://doaj.org/toc/1999-4923Renal 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.Natsuko OyamaMaho KawaguchiKeiji ItakaShigeru KawakamiMDPI AGarticlemessenger RNA (mRNA)mRNA therapeuticspolyplex nanomicellekidneyrenal pelvis injectionhydrodynamic injectionPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1810, p 1810 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	messenger RNA (mRNA) mRNA therapeutics polyplex nanomicelle kidney renal pelvis injection hydrodynamic injection Pharmacy and materia medica RS1-441
spellingShingle	messenger RNA (mRNA) mRNA therapeutics polyplex nanomicelle kidney renal pelvis injection hydrodynamic injection Pharmacy and materia medica RS1-441 Natsuko Oyama Maho Kawaguchi Keiji Itaka Shigeru Kawakami Efficient Messenger RNA Delivery to the Kidney Using Renal Pelvis Injection in Mice
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.
format	article
author	Natsuko Oyama Maho Kawaguchi Keiji Itaka Shigeru Kawakami
author_facet	Natsuko Oyama Maho Kawaguchi Keiji Itaka Shigeru Kawakami
author_sort	Natsuko Oyama
title	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_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_sort	efficient messenger rna delivery to the kidney using renal pelvis injection in mice
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/fcae87e9a1ee4988aeb9d5cb3859540f
work_keys_str_mv	AT natsukooyama efficientmessengerrnadeliverytothekidneyusingrenalpelvisinjectioninmice AT mahokawaguchi efficientmessengerrnadeliverytothekidneyusingrenalpelvisinjectioninmice AT keijiitaka efficientmessengerrnadeliverytothekidneyusingrenalpelvisinjectioninmice AT shigerukawakami efficientmessengerrnadeliverytothekidneyusingrenalpelvisinjectioninmice
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Efficient Messenger RNA Delivery to the Kidney Using Renal Pelvis Injection in Mice

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