Figure 1.

Antisense oligonucleotides (ASOs) reduce RNA foci in HT1080 cells. (a) Diagram of pLC15-F construct for expression of expanded-CUG repeats in the DMPK 3′ UTR. The attB site supports genomic integration by PhiC31 integrase. CMV/CBA, CMV enhancer/chicken β-actin promoter; puro, puromycin resistance. (b) Sequence of LNA-ASOs. The position of locked nucleic acid (LNA)-modified subunits is shown by upper case letters, lower case letters are unmodified DNA. Gapmer and mixmer ASOs have full phosphorothioate backbones. (c) FISH showing foci of CUG^exp RNA (red) in nuclei (blue) of stably transfected HT1080 cells. (d) Histogram showing the percentage of cells with nuclear foci of CUG^exp RNA. The number of cells counted was 526 for no treatment, 300 for gapmer-treatment, and 398 for blocker-treatment. Mean ± SD, n = 3 or more. *P < 0.001. ASO, antisense oligonucleotide; CMV, cytomegalovirus.