By: IPP Bureau
Last updated : August 29, 2026 7:47 am
Engineered tRNA restores full-length protein production in cystic fibrosis models, opening the door to a potential new class of RNA therapeutics
Researchers at the University of Toronto have developed a next-generation RNA therapeutic approach that could potentially treat a broad range of genetic diseases caused by a common class of disease-causing mutations.
The work advances an emerging platform in genetic medicine centred on transfer RNA, or tRNA. The researchers engineered tRNA to help cells read through premature stop signals in genetic instructions, allowing them to complete production of full-length proteins that would otherwise be truncated or absent.
Study lead Bowen Li, associate professor at the University of Toronto’s Leslie Dan Faculty of Pharmacy and an affiliate scientist at the University Health Network’s Princess Margaret Cancer Centre, said the research could lay the foundation for a new class of drugs designed to treat multiple genetic diseases through a common therapeutic strategy.
“There are so many types of disease-causing mutations – many affecting only a small number of people – that developing a separate gene therapy for every individual mutation is extremely challenging,” says Li.
“With tRNA therapeutics, our goal is to develop a common therapeutic approach that could potentially address the same type of mutation across many different genes and diseases, including rare conditions that currently have few or no effective treatment options.”
Li and his team focused on nonsense mutations, which introduce a premature stop signal into the genetic instructions used to produce a protein. As a result, cells may produce little or no full-length functional protein, disrupting vital biological functions.
Although nonsense mutations are estimated to cause about 11 per cent of inherited genetic disorders, they are implicated in thousands of conditions, including subsets of cystic fibrosis and certain muscular and neurological diseases.
The study, published in Science on August 27, demonstrates that engineered tRNA can suppress disease-causing nonsense mutations and restore full-length protein production across a series of laboratory and preclinical models of cystic fibrosis.
The researchers also found that the approach can be combined with existing cystic fibrosis medicines, pointing to the potential for combination therapy.
“The same type of premature stop signal can occur in many different genes, causing diseases that affect the lungs, brain, muscles and other tissues”, says Li. “Our long-term goal is to develop tRNA medicines that recognize these shared stop signals, so that one therapeutic strategy could potentially be applied across many different genetic diseases.”
Study co-lead Haissi Cui, assistant professor of chemistry in the Faculty of Arts & Science, helped guide the team towards a novel strategy involving the chemical modifications naturally found in tRNAs.
“Interdisciplinary collaboration was key to this project,” says Cui. “We used nature as our design guide and found that adding one specific modification made the engineered tRNA more active and longer-lasting. It shows what becomes possible when chemistry and RNA biology come together.”
The researchers then faced another challenge: delivering the engineered tRNA into the cells where it was needed.
Jingan (Charles) Chen, a researcher in Li’s laboratory and co-lead author of the study, said the team turned to lipid nanoparticles, which have previously been used to deliver mRNA in COVID-19 vaccines, but redesigned the technology for tRNA delivery.
“No matter how powerful you make those tRNAs, without delivery, they cannot be a drug,” says Chen, a PhD candidate in the Leslie Dan Faculty of Pharmacy and the Institute of Biomedical Engineering.
“That cargo-specific delivery system is one of the major advances of our study. We used a tailored lipid nanoparticle delivery system that is specifically developed for tRNA.”