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...

Ausführliche Beschreibung

Bibliographische Detailangaben
Hauptverfasser: 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: Artikel
Sprache:English
Veröffentlicht: Nature Portfolio 2018-02-01
Schriftenreihe:Nature Communications
Online Zugang:https://doi.org/10.1038/s41467-018-02989-4

Online

https://doi.org/10.1038/s41467-018-02989-4

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