In vivo biodistribution analysis of transmission competent and defective RNA virus-based episomal vector

Abstract RNA virus-based episomal vector (REVec) is an emerging viral vector system that mediates long-term stable gene expression in variety of cell types in vitro. However, little is known about its tissue tropism and persistence of gene expression in vivo. Here, to evaluate the feasibility of REV...

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Autores principales:	Yumiko Komatsu, Chiaki Tanaka, Ryo Komorizono, Keizo Tomonaga
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6e878e2e13f3437185c1a461dc15a8d6
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spelling	oai:doaj.org-article:6e878e2e13f3437185c1a461dc15a8d62021-12-02T18:18:07ZIn vivo biodistribution analysis of transmission competent and defective RNA virus-based episomal vector10.1038/s41598-020-62630-72045-2322https://doaj.org/article/6e878e2e13f3437185c1a461dc15a8d62020-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-62630-7https://doaj.org/toc/2045-2322Abstract RNA virus-based episomal vector (REVec) is an emerging viral vector system that mediates long-term stable gene expression in variety of cell types in vitro. However, little is known about its tissue tropism and persistence of gene expression in vivo. Here, to evaluate the feasibility of REVec for in vivo gene delivery, we conducted biodistribution analysis of transmission competent REVec and transmission defective ΔG-REVec in Lewis rats. Following intracranial administration of REVec, transgene expression was detected in various tissues. In contrast, transgene expression was only observed in the brain after ΔG-REVec administration. Low levels of vector shedding in the feces and blood and of neutralizing antibody in the serum were detected after REVec injection. In the brain, microglia, astrocytes and neurons were susceptible to REVec-mediated transduction. However, the animals administered with REVec, but not with ΔG-REVec showed a significant decrease in body weight compared to mock treated animals. Additionally, CD8 T cell infiltration was observed in the brain of these animals. In summary, we demonstrated that REVec promotes long-term transgene expression in vivo without causing high vector shedding or neutralizing antibody production; however, suggests the need to attenuate vector associated pathogenicity in the future.Yumiko KomatsuChiaki TanakaRyo KomorizonoKeizo TomonagaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yumiko Komatsu Chiaki Tanaka Ryo Komorizono Keizo Tomonaga In vivo biodistribution analysis of transmission competent and defective RNA virus-based episomal vector
description	Abstract RNA virus-based episomal vector (REVec) is an emerging viral vector system that mediates long-term stable gene expression in variety of cell types in vitro. However, little is known about its tissue tropism and persistence of gene expression in vivo. Here, to evaluate the feasibility of REVec for in vivo gene delivery, we conducted biodistribution analysis of transmission competent REVec and transmission defective ΔG-REVec in Lewis rats. Following intracranial administration of REVec, transgene expression was detected in various tissues. In contrast, transgene expression was only observed in the brain after ΔG-REVec administration. Low levels of vector shedding in the feces and blood and of neutralizing antibody in the serum were detected after REVec injection. In the brain, microglia, astrocytes and neurons were susceptible to REVec-mediated transduction. However, the animals administered with REVec, but not with ΔG-REVec showed a significant decrease in body weight compared to mock treated animals. Additionally, CD8 T cell infiltration was observed in the brain of these animals. In summary, we demonstrated that REVec promotes long-term transgene expression in vivo without causing high vector shedding or neutralizing antibody production; however, suggests the need to attenuate vector associated pathogenicity in the future.
format	article
author	Yumiko Komatsu Chiaki Tanaka Ryo Komorizono Keizo Tomonaga
author_facet	Yumiko Komatsu Chiaki Tanaka Ryo Komorizono Keizo Tomonaga
author_sort	Yumiko Komatsu
title	In vivo biodistribution analysis of transmission competent and defective RNA virus-based episomal vector
title_short	In vivo biodistribution analysis of transmission competent and defective RNA virus-based episomal vector
title_full	In vivo biodistribution analysis of transmission competent and defective RNA virus-based episomal vector
title_fullStr	In vivo biodistribution analysis of transmission competent and defective RNA virus-based episomal vector
title_full_unstemmed	In vivo biodistribution analysis of transmission competent and defective RNA virus-based episomal vector
title_sort	in vivo biodistribution analysis of transmission competent and defective rna virus-based episomal vector
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/6e878e2e13f3437185c1a461dc15a8d6
work_keys_str_mv	AT yumikokomatsu invivobiodistributionanalysisoftransmissioncompetentanddefectivernavirusbasedepisomalvector AT chiakitanaka invivobiodistributionanalysisoftransmissioncompetentanddefectivernavirusbasedepisomalvector AT ryokomorizono invivobiodistributionanalysisoftransmissioncompetentanddefectivernavirusbasedepisomalvector AT keizotomonaga invivobiodistributionanalysisoftransmissioncompetentanddefectivernavirusbasedepisomalvector
_version_	1718378281403678720

In vivo biodistribution analysis of transmission competent and defective RNA virus-based episomal vector

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