Sequence motifs associated with hepatotoxicity of locked nucleic acid—modified antisense oligonucleotides
نویسندگان
چکیده
منابع مشابه
Sequence motifs associated with hepatotoxicity of locked nucleic acid—modified antisense oligonucleotides
Fully phosphorothioate antisense oligonucleotides (ASOs) with locked nucleic acids (LNAs) improve target affinity, RNase H activation and stability. LNA modified ASOs can cause hepatotoxicity, and this risk is currently not fully understood. In vitro cytotoxicity screens have not been reliable predictors of hepatic toxicity in non-clinical testing; however, mice are considered to be a sensitive...
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Gapmer antisense oligonucleotides cleave target RNA effectively in vivo, and is considered as promising therapeutics. Especially, gapmers modified with locked nucleic acid (LNA) shows potent knockdown activity; however, they also cause hepatotoxic side effects. For developing safe and effective gapmer drugs, a deeper understanding of the mechanisms of hepatotoxicity is required. Here, we invest...
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ژورنال
عنوان ژورنال: Nucleic Acids Research
سال: 2014
ISSN: 1362-4962,0305-1048
DOI: 10.1093/nar/gku142