Scientists design new RNA therapy to bypass mutations behind thousands of genetic diseases
Scientists engineered transfer RNA to bypass premature genetic stop signals and restore production of full-length proteins in cystic fibrosis models. A single chemical modification increased some engineered tRNAs’ activity, while a custom lipid nanoparticle delivered the therapy to key airway cells. Because the same premature stop signals appear across many genes, the approach could eventually provide a common treatment strategy for multiple genetic diseases. A small error in genetic instructions can bring protein production to an abrupt halt. Instead of building the complete molecule a cell needs, its machinery encounters a premature stop signal and produces a shortened protein, or sometimes almost none at all. Scientists at the University of Toronto have now developed an RNA-based approach designed to get past those faulty stop signs. By chemically modifying transfer RNA, or tRNA, and packaging it inside specially designed lipid nanoparticles, the researchers restored full-length proteins in laboratory, animal and patient-derived models of cystic fibrosis. The study focuses on so-called nonsense mutations, which account for about 11% of inherited genetic disorders. Because the same types of …


