Double-stranded DNA invasion by anti-gene oligonucleotide clamps

Anti-gene oligonucleotides (AGOs) have been developed to target genomic DNA, which can regulate gene expression to curb the root cause of diseases. In this issue of Molecular Therapy Nucleic Acids, Umek et al. reported a promising AGO with a clamp design to target the double-stranded DNA (dsDNA). Umek et al. designed a series of mixmers made of locked nucleic acid (LNA), DNA, and phosphorothioate (PS) to target the Huntington (HTT) gene.1 This AGO effectively knocked down HTT mRNA expression in patient-derived fibroblasts of Huntington’s disease (HD).