Duplex RNAs and ss-siRNAs Block RNA Foci Associated with Fuchs' Endothelial Corneal Dystrophy

Fuchs' endothelial corneal dystrophy (FECD) leads to vision loss and is one of the most common inherited eye diseases. Corneal transplants are the only curative treatment available, and there is a major unmet need for treatments that are less invasive and independent of donor tissue. Most cases of FECD are associated with an expanded CUG repeat within the intronic region of TCF4 and the mutant RNA has been implicated as the cause of the disease. We previously presented preliminary data suggesting that single-stranded antisense oligonucleotides (ASOs) can inhibit CUG RNA foci in patient-derived cells and tissue. We now show that duplex RNAs and single-stranded silencing RNAs (ss-siRNAs) reduce the number of cells with foci and the number of foci per cells. Potencies are similar to those that are achieved with chemically modified ASOs designed to block foci. These data widen the potential for synthetic nucleic acids to be used to treat a widely prevalent and debilitating disease.