title: SMRT compounds correct nonsense mutations in primary immunodeficiency and other genetic models.
abstract: Within less than 10 years after the realization of the double helix of DNA, the ability of aminoglycosides to influence the misreading or readthrough of premature termination codons was discovered. It took another three decades to clone and sequence disease genes and appreciate the similarity of mutation spectra for most inborn errors. Nonsense mutations once again have become the target of readthrough compounds. In this brief review, we trace the development in our laboratory of the next generation of readthrough agents, small molecule readthrough (SMRT) drug-like chemicals, and assays for comparing their in vitro activity. Possible mechanisms of action and potential clinical applications are considered.
authors.affiliation: David Geffen/UCLA School of Medicine, Department of Pathology and Laboratory Medicine, and Human Genetics, Los Angeles, California 90095-1732, USA. rgatti@mednet.ucla.edu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gatti
mesh_terms: D000617:Aminoglycosides / Q000627:therapeutic use*; D000818:Animals; D018389:Codon, Nonsense; D017074:Common Variable Immunodeficiency / Q000188:drug therapy* / Q000235:genetics*; D030342:Genetic Diseases, Inborn / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics
chemical_list: D000617:Aminoglycosides; D018389:Codon, Nonsense