Antisense Oligonucleotides

Overview

Single-stranded synthetic nucleic acid analogs used to modulate gene expression by binding mRNA or nuclear RNA; the first oligonucleotide modality with a 40+ year development arc from 1978 discovery to a broad clinical pipeline. The first ASO biology was discovered in 1978, but it took 20 years before the first ASO drug was approved, and another 15 years before the second — totaling 35 years from discovery before the field began to flourish. By 2016 three ASOs were approved simultaneously including Spinraza and eteplirsen; by 2025 over 80 oligonucleotide candidates existed; by 2026 over 340 nucleic acid drugs are in active clinical development (not preclinical). (Segment 2 (05:00-10:00) / Segment 3 (10:00-15:00))