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siRNA sequence and chemical structures of mononucleotides (A) Schematic of the parent siRNA duplex targeting human PCSK9. This siRNA was previously characterized. (B) Structures of 2′-OMe, 2′-F, ( S )-GNA, natural phosphate, and phosphorothioate linkages. (C) Structures of 2′-modified mononucleotides used in this study.

Journal: Molecular Therapy. Nucleic Acids

Article Title: 2′-Ribose-modified nucleotides: A strategy for reducing off-target effects of oligonucleotide drugs

doi: 10.1016/j.omtn.2026.102835

Figure Lengend Snippet: siRNA sequence and chemical structures of mononucleotides (A) Schematic of the parent siRNA duplex targeting human PCSK9. This siRNA was previously characterized. (B) Structures of 2′-OMe, 2′-F, ( S )-GNA, natural phosphate, and phosphorothioate linkages. (C) Structures of 2′-modified mononucleotides used in this study.

Article Snippet: To address this issue, Alnylam Pharmaceuticals has employed GNA modification at position 7 of the siRNA antisense strand to disrupt the seed region, thereby significantly reducing off-target effects and alleviating hepatocellular toxicity.

Techniques: Sequencing, Modification