Aminoglycoside-induced Translational Read-through in Disease: Overcoming Nonsense Mutations by Pharmacogenetic Therapy

doi:doi:10.1038/sj.clpt.6100012

Clinical Pharmacology & Therapeutics homepage

Clinical Pharmacology & Therapeutics (2007) 81, 99–103. doi:10.1038/sj.clpt.6100012

Aminoglycoside-induced Translational Read-through in Disease: Overcoming Nonsense Mutations by Pharmacogenetic Therapy

L V Zingman^1,2, S Park^1,2, T M Olson^1,2, A E Alekseev^1,2 and A Terzic^1,2

¹Marriott Heart Disease Research Program, Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA
²Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA

Correspondence: LV Zingman, (zingman.leonid@mayo.edu)

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Abstract

A third of inherited diseases result from premature termination codon mutations. Aminoglycosides have emerged as vanguard pharmacogenetic agents in treating human genetic disorders due to their unique ability to suppress gene translation termination induced by nonsense mutations. In preclinical and pilot clinical studies, this therapeutic approach shows promise in phenotype correction by promoting otherwise defective protein synthesis. The challenge ahead is to maximize efficacy while preventing interaction with normal protein production and function.