Figure 1

Design of skip 27 ASOs. The sequences of the intronic regions flanking exon 27 and parts of exon 27 are shown at the top – intronic sequences are in small letters, exonic sequences are in caps, exon 27 is enclosed in the grey-shaded box. The splice-sites (BPS = branch-point sequence; 3'ss = 3' splice-site; 5'ss = 5' splice-site) are outlined with dotted lines. The Shapiro and Senapathy (S&S) scores below each splice-site reflect the degree of similarity of these sequences to the splice-site consensus [9]. The ASO design is indicated below. Arrows run in the 5' to 3' direction. Three classes of ASO tested are distinguished within each box: single splice site ASOs that target individual splice sites; combination splice-site ASOs that target two splice-sites simultaneously; combination splice-site ASOs that target two splice-sites and are linked to an hnRNP A1 binding tail (A1 – the sequence of this tail is presented) or a mutated tail that is unable to bind hnRNP A1 (mut A1).