Antisense therapy is currently one of the most promising strategies for treating SMA. Antisense oligonucleotides (AONs) are used to block intronic splicing silencer sites such as N1 (ISS-N1) on intron 7 of SMN2, which induces the inclusion of exon 7 and, consequently, leads to the recovery of functional SMN protein expression from the endogenous SMN2 gene7. A 20-mer AON with phosphorothioate backbones and 2′-O-methyl (2′OMeP) modification was the first AON to show the efficacy of AONs in vitro for SMN2 7. Nusinersen/IONIS-SMNRx (Spinraza), an 18-mer AON with phosphorothioate backbones and 2′-O-methoxyethyl modification (MOE), increased the exon 7 inclusion and rescued SMA phenotypes in vivo in mouse models8–11. Following the completion of Phase I/II trials with encouraging data, nusinersen has recently been approved by the U.S. Food and Drug Administration (FDA) and became the first drug for the treatment of SMA12–14.