Internal Introns Promote Backsplicing to Generate Circular RNAs from Spinal Muscular Atrophy Gene.

Human () codes for SMN, an essential housekeeping protein involved in most aspects of RNA metabolism. Deletions or mutations of lead to spinal muscular atrophy (SMA), a devastating neurodegenerative disease linked to a high rate of infant mortality. , a near identical copy of present in humans, cannot compensate for the loss of due to predominant skipping of exon 7.

High Concentration of an ISS-N1-Targeting Antisense Oligonucleotide Causes Massive Perturbation of the Transcriptome.

Intronic splicing silencer N1 (ISS-N1) located within () intron 7 is the target of a therapeutic antisense oligonucleotide (ASO), nusinersen (Spinraza), which is currently being used for the treatment of spinal muscular atrophy (SMA), a leading genetic disease associated with infant mortality. The discovery of ISS-N1 as a promising therapeutic target was enabled in part by Anti-N1, a 20-mer ASO that restored exon 7 inclusion by annealing to ISS-N1. Here, we analyzed the transcriptome of SMA patient cells treated with 100 nM of Anti-N1 for 30 h.