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

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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Main Authors: 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
Format: article
Language:EN
Published: Nature Portfolio 2018
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Science
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Online Access:https://doaj.org/article/c6e811a8256f42f19ee8c93f99cf1382
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https://doaj.org/article/c6e811a8256f42f19ee8c93f99cf1382

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