Strategies to Correct Nonsense Mutations

Since a nonsense mutation is responsible for the pathology in about 10% of genetic diseases, therapeutic approaches have been developed or are in developing stages to correct nonsense mutations. Few of them are exclusive to nonsense mutations, such as the inhibition of nonsense-mediated mRNA decay or the activation of readthrough. However, most of them have been designed to apply to various types of mutations, in order to benefit the highest number of patients. Those nonspecific therapeutic approaches fix the mutation at different levels, such as the DNA level, like gene therapy or genome editing; the RNA level with the exon skipping, pseudouridylation, or trans -splicing; or the cellular level with cell therapy. All these therapeutic approaches are in progress and reached clinical trial step for some of them, while others are still at the preclinical stage. The main therapeutic approaches that can apply to the correction of nonsense mutations will be described.