ASO drug Qalsody (tofersen) targets amyotrophic lateral sclerosis

STRUCTURE: Tofersen, an antisense oligonucleotide (ASO) drug, is a 20-base residue with an RNA–DNA–RNA (5–10–5) gapmer mixed backbone oligonucleotide. Within the molecule, there are 19 inter-nucleotide linkages, with 15 of them being 3′-O to 5′-O phosphorothioate diesters and the remaining four being 3′-O to 5′-O phosphate diesters. In terms of sugar residues, ten out of the 20 are 2-deoxy-d-ribose, while the others consist of 2′-O-(2-methoxyethyl)-d-ribose (2′-MOE). The arrangement of residues involves five MOE nucleosides located at both the 5′ and 3′ ends, surrounding a central gap containing ten 2′-MOE.