A flow cytometry-based reporter assay identifies macrolide antibiotics as nonsense mutation read-through agents

A large number of human diseases are caused by nonsense mutations. these mutations result in premature protein termination and the expression of truncated, usually nonfunctional products. a promising therapeutic strategy for patients suffering from premature termination codon (ptc)-mediated disorders is to suppress the nonsense mutation and restore the expression of the affected protein. such a suppression approach using specific antibiotics and other read-through promoting agents has been shown to suppress ptcs and restore the production of several important proteins. here, we report the establishment of a novel, rapid, and very efficient method for screening stop-codon read-through agents. we also show that, in both mammalian cells and in a transgenic mouse model, distinct members of the macrolide antibiotic family can induce read-through of disease-causing stop codons leading to re-expression of several key proteins and to reduced disease phenotypes. taken together, our results help in the identification and characterization of well-needed customized pharmaceutical ptc suppression agents.