FIGURE 4.

Effect of the local context on antisense response of ISS-N1-targeting ASOs. (A) Diagrammatic representation of the target area in intron 7 of SMN2 minigene and its four mutants. ISS-N1 is highlighted in gray. The first C residue in ISS-N1 is marked as ¹⁰C or ¹⁵C, depending on its position relative to the beginning of intron 7. Of note, numbering of intronic residues starts with the first position of intron 7. Five-nt-long insertions immediately upstream of ISS-N1 in SMN2/5A or SMN2/5G minigenes are boxed and shown in capital letters. (B) In vivo splicing pattern of wild-type and mutant SMN2 minigenes shown in panel A. The minigenes were cotransfected with an ASO of interest. Cotransfections and splicing analysis were done similarly as in Figure 2A.