The adeno-associated virus rh10 vector is an effective gene transfer system for chronic spinal cord injury

Abstract Treatment options for chronic spinal cord injury (SCI) remain limited due to unfavourable changes in the microenvironment. Gene therapy can overcome these barriers through continuous delivery of therapeutic gene products to the target tissue. In particular, adeno-associated virus (AAV) vect...

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Autores principales:	Yutaka Hoshino, Kenji Nishide, Narihito Nagoshi, Shinsuke Shibata, Nobuko Moritoki, Kota Kojima, Osahiko Tsuji, Morio Matsumoto, Jun Kohyama, Masaya Nakamura, Hideyuki Okano
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d5b08ffb7498436c8cf2dee218ce595c
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spelling	oai:doaj.org-article:d5b08ffb7498436c8cf2dee218ce595c2021-12-02T15:09:58ZThe adeno-associated virus rh10 vector is an effective gene transfer system for chronic spinal cord injury10.1038/s41598-019-46069-z2045-2322https://doaj.org/article/d5b08ffb7498436c8cf2dee218ce595c2019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-46069-zhttps://doaj.org/toc/2045-2322Abstract Treatment options for chronic spinal cord injury (SCI) remain limited due to unfavourable changes in the microenvironment. Gene therapy can overcome these barriers through continuous delivery of therapeutic gene products to the target tissue. In particular, adeno-associated virus (AAV) vectors are potential candidates for use in chronic SCI, considering their safety and stable gene expression in vivo. Given that different AAV serotypes display different cellular tropisms, it is extremely important to select an optimal serotype for establishing a gene transfer system during the chronic phase of SCI. Therefore, we generated multiple AAV serotypes expressing ffLuc-cp156, a fusion protein of firefly luciferase and Venus, a variant of yellow fluorescent protein with fast and efficient maturation, as a reporter, and we performed intraparenchymal injection in a chronic SCI mouse model. Among the various serotypes tested, AAVrh10 displayed the highest photon count on bioluminescence imaging. Immunohistological analysis revealed that AAVrh10 showed favourable tropism for neurons, astrocytes, and oligodendrocytes. Additionally, with AAVrh10, the area expressing Venus was larger in the injury epicentre and extended to the surrounding tissue. Furthermore, the fluorescence intensity was significantly higher with AAVrh10 than with the other vectors. These results indicate that AAVrh10 may be an appropriate serotype for gene delivery to the chronically injured spinal cord. This promising tool may be applied for research and development related to the treatment of chronic SCI.Yutaka HoshinoKenji NishideNarihito NagoshiShinsuke ShibataNobuko MoritokiKota KojimaOsahiko TsujiMorio MatsumotoJun KohyamaMasaya NakamuraHideyuki OkanoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yutaka Hoshino Kenji Nishide Narihito Nagoshi Shinsuke Shibata Nobuko Moritoki Kota Kojima Osahiko Tsuji Morio Matsumoto Jun Kohyama Masaya Nakamura Hideyuki Okano The adeno-associated virus rh10 vector is an effective gene transfer system for chronic spinal cord injury
description	Abstract Treatment options for chronic spinal cord injury (SCI) remain limited due to unfavourable changes in the microenvironment. Gene therapy can overcome these barriers through continuous delivery of therapeutic gene products to the target tissue. In particular, adeno-associated virus (AAV) vectors are potential candidates for use in chronic SCI, considering their safety and stable gene expression in vivo. Given that different AAV serotypes display different cellular tropisms, it is extremely important to select an optimal serotype for establishing a gene transfer system during the chronic phase of SCI. Therefore, we generated multiple AAV serotypes expressing ffLuc-cp156, a fusion protein of firefly luciferase and Venus, a variant of yellow fluorescent protein with fast and efficient maturation, as a reporter, and we performed intraparenchymal injection in a chronic SCI mouse model. Among the various serotypes tested, AAVrh10 displayed the highest photon count on bioluminescence imaging. Immunohistological analysis revealed that AAVrh10 showed favourable tropism for neurons, astrocytes, and oligodendrocytes. Additionally, with AAVrh10, the area expressing Venus was larger in the injury epicentre and extended to the surrounding tissue. Furthermore, the fluorescence intensity was significantly higher with AAVrh10 than with the other vectors. These results indicate that AAVrh10 may be an appropriate serotype for gene delivery to the chronically injured spinal cord. This promising tool may be applied for research and development related to the treatment of chronic SCI.
format	article
author	Yutaka Hoshino Kenji Nishide Narihito Nagoshi Shinsuke Shibata Nobuko Moritoki Kota Kojima Osahiko Tsuji Morio Matsumoto Jun Kohyama Masaya Nakamura Hideyuki Okano
author_facet	Yutaka Hoshino Kenji Nishide Narihito Nagoshi Shinsuke Shibata Nobuko Moritoki Kota Kojima Osahiko Tsuji Morio Matsumoto Jun Kohyama Masaya Nakamura Hideyuki Okano
author_sort	Yutaka Hoshino
title	The adeno-associated virus rh10 vector is an effective gene transfer system for chronic spinal cord injury
title_short	The adeno-associated virus rh10 vector is an effective gene transfer system for chronic spinal cord injury
title_full	The adeno-associated virus rh10 vector is an effective gene transfer system for chronic spinal cord injury
title_fullStr	The adeno-associated virus rh10 vector is an effective gene transfer system for chronic spinal cord injury
title_full_unstemmed	The adeno-associated virus rh10 vector is an effective gene transfer system for chronic spinal cord injury
title_sort	adeno-associated virus rh10 vector is an effective gene transfer system for chronic spinal cord injury
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/d5b08ffb7498436c8cf2dee218ce595c
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The adeno-associated virus rh10 vector is an effective gene transfer system for chronic spinal cord injury

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