Antisense oligonucleotides targeting the promoter region of the SMN2 gene in preclinical development in SMA

A Chinese team studied the effects of two antisense oligonucleotides targeting a key region of the methylation of the promoter of the SMN2 gene, in cell cultures derived from patients with SMA and in mice with a severe SMA phenotype.

The results show that:

  • transcription and overall expression of the SMN protein are improved following the addition of oligonucleotides to patient cell cultures, similar benefits are observed after treatment of these same cells with nusinersen;
  • intrathecal administration of one of the two oligonucleotides (ASO-P1) is capable, in severe SMA mice, of correcting the disease phenotype and increasing survival;
  • ASO-P1 restores the level of transcription of the gene but does not correct the skipping of exon 7;
  • the combination of ASO-P1 and nusinersen in SMA cell lines increases functional SMN protein levels more than nusinersen alone or ASO-P1 alone.


Antisense oligonucleotides targeting the SMN2 promoter region enhance SMN2 expression in spinal muscular atrophy cell lines and mouse model. Wang J, Bai J, OuYang Set al. Hum Mol Genet. 2021 Dec 9:ddab350.