Oligonucleotide Therapeutics

ASOs, siRNAs and aptamers are reshaping rare and common disease therapy with multiple FDA approvals. The session covers tofersen (Qalsody) for SOD1 ALS, ulefnersen and branaplam, GalNAc-conjugated siRNAs (inclisiran, vutrisiran, patisiran), ADAR-recruiting oligonucleotides for RNA editing (Wave WVE-006, Korro), and exon-skipping approaches in DMD. Discussion addresses delivery and tissue specificity beyond liver, the comparison of ASO chemistries (2'-MOE, cEt, LNA, PMO), conjugation strategies (GalNAc, fatty acid, peptide), immunogenicity considerations, and the manufacturing economics of oligonucleotide therapeutics.