Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity

A subset of chemically-modified siRNAs conjugated to trivalent GalNAc may fail during nonclinical development due to rat hepatotoxicity. Here, the authors show that hepatotoxicity may be accounted for by microRNA-like off-target effects of siRNA and can be mitigated by a thermally destabilizing modi...

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Autores principales:	Maja M. Janas, Mark K. Schlegel, Carole E. Harbison, Vedat O. Yilmaz, Yongfeng Jiang, Rubina Parmar, Ivan Zlatev, Adam Castoreno, Huilei Xu, Svetlana Shulga-Morskaya, Kallanthottathil G. Rajeev, Muthiah Manoharan, Natalie D. Keirstead, Martin A. Maier, Vasant Jadhav
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Science Q
Acceso en línea:	https://doaj.org/article/c6e811a8256f42f19ee8c93f99cf1382
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spelling	oai:doaj.org-article:c6e811a8256f42f19ee8c93f99cf13822021-12-02T15:34:15ZSelection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity10.1038/s41467-018-02989-42041-1723https://doaj.org/article/c6e811a8256f42f19ee8c93f99cf13822018-02-01T00:00:00Zhttps://doi.org/10.1038/s41467-018-02989-4https://doaj.org/toc/2041-1723A subset of chemically-modified siRNAs conjugated to trivalent GalNAc may fail during nonclinical development due to rat hepatotoxicity. Here, the authors show that hepatotoxicity may be accounted for by microRNA-like off-target effects of siRNA and can be mitigated by a thermally destabilizing modification in the siRNA seed region.Maja M. JanasMark K. SchlegelCarole E. HarbisonVedat O. YilmazYongfeng JiangRubina ParmarIvan ZlatevAdam CastorenoHuilei XuSvetlana Shulga-MorskayaKallanthottathil G. RajeevMuthiah ManoharanNatalie D. KeirsteadMartin A. MaierVasant JadhavNature PortfolioarticleScienceQENNature Communications, Vol 9, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Science Q
spellingShingle	Science Q Maja M. Janas Mark K. Schlegel Carole E. Harbison Vedat O. Yilmaz Yongfeng Jiang Rubina Parmar Ivan Zlatev Adam Castoreno Huilei Xu Svetlana Shulga-Morskaya Kallanthottathil G. Rajeev Muthiah Manoharan Natalie D. Keirstead Martin A. Maier Vasant Jadhav Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity
description	A subset of chemically-modified siRNAs conjugated to trivalent GalNAc may fail during nonclinical development due to rat hepatotoxicity. Here, the authors show that hepatotoxicity may be accounted for by microRNA-like off-target effects of siRNA and can be mitigated by a thermally destabilizing modification in the siRNA seed region.
format	article
author	Maja M. Janas Mark K. Schlegel Carole E. Harbison Vedat O. Yilmaz Yongfeng Jiang Rubina Parmar Ivan Zlatev Adam Castoreno Huilei Xu Svetlana Shulga-Morskaya Kallanthottathil G. Rajeev Muthiah Manoharan Natalie D. Keirstead Martin A. Maier Vasant Jadhav
author_facet	Maja M. Janas Mark K. Schlegel Carole E. Harbison Vedat O. Yilmaz Yongfeng Jiang Rubina Parmar Ivan Zlatev Adam Castoreno Huilei Xu Svetlana Shulga-Morskaya Kallanthottathil G. Rajeev Muthiah Manoharan Natalie D. Keirstead Martin A. Maier Vasant Jadhav
author_sort	Maja M. Janas
title	Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity
title_short	Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity
title_full	Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity
title_fullStr	Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity
title_full_unstemmed	Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity
title_sort	selection of galnac-conjugated sirnas with limited off-target-driven rat hepatotoxicity
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/c6e811a8256f42f19ee8c93f99cf1382
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Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity

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