Novel gene therapy approach creates new route to tackle rare, inherited diseases

Nonsense mutations are single-letter errors in the genetic code that prematurely halt the production of critical proteins. These unfinished proteins are unable to function normally, and nonsense mutations cause 10-15 percent of all inherited genetic diseases, including Duchenne muscular dystrophy, spinal muscular atrophy, cystic fibrosis, and polycystic kidney disease. There is currently no cure or broadly effective treatment for these often devastating conditions that are individually rare but estimated to collectively affect up to 30 million people worldwide.
A new study, led by Christopher Ahern, Ph.D., at the University of Iowa Carver College of Medicine, reveals a novel approach and robust technology platform for suppressing nonsense mutations using engineered transfer RNA (tRNA) molecules. The research by Ahern, his UI colleagues, and collaborators at The Wistar Institute in Philadelphia, the Cystic Fibrosis Foundation Therapeutics Lab in Lexington, Mass., and Integrated DNA Technologies Inc. in Coralville, Iowa, shows that modified tRNAs can efficiently and accurately repair nonsense mutations with any amino acid. The findings were published Feb. 18 in Nature Communications.