For any antisense-based approach, discrimination between alleles based on a single-nucleotide difference presents as a potential pitfall in terms of concomitant downregulation of the wild-type allele.22, 23, 24 Recently published AONs directed against a mutation in NR2E3, causative for dominantly inherited retinitis pigmentosa, also significantly reduced the wild-type transcript and protein levels.21 This evidence concerns the gene NR2E3 and retinitis pigmentosa.