The Combination of Mesyl-Phosphoramidate Inter-Nucleotide Linkages and 2′-O-Methyl in Selected Positions in the Antisense Oligonucleotide Enhances the Performance of RNaseH1 Active PS-ASOs
Author:
Affiliation:
1. Department of Core Antisense Research, Ionis Pharmaceuticals, Inc., Carlsbad, California, USA.
Publisher
Mary Ann Liebert Inc
Subject
Drug Discovery,Genetics,Molecular Biology,Molecular Medicine,Biochemistry
Link
https://www.liebertpub.com/doi/pdf/10.1089/nat.2022.0005
Reference20 articles.
1. Sequence motifs associated with hepatotoxicity of locked nucleic acid—modified antisense oligonucleotides
2. Development of a Method for Profiling Protein Interactions with LNA-Modified Antisense Oligonucleotides Using Protein Microarrays
3. Acute hepatotoxicity of 2′ fluoro-modified 5–10–5 gapmer phosphorothioate oligonucleotides in mice correlates with intracellular protein binding and the loss of DBHS proteins
4. 2′-Fluoro-modified phosphorothioate oligonucleotide can cause rapid degradation of P54nrb and PSF
5. Chemical modification of PS-ASO therapeutics reduces cellular protein-binding and improves the therapeutic index
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