Bowen Li, PhD

In the past 20 years, small molecule drugs developed for cystic fibrosis (CF) have improved quality of life—and extended life—for 90% of patients who inherit the disease. But for Dr. Bowen Li and his team at University of Toronto (U of T), that’s not enough. Sometimes the drugs lose effectiveness, cause side effects, and in 10% of patients, they don’t work. The Li team is optimizing a novel therapeutic using lipid nanoparticle (LNP) technology to deliver transfer RNA (tRNA) that potentially could help all patients live normal lives.

In CF, a premature stop codon (DNA error) in the CF transmembrane conductance regulator (CFTR) gene creates what’s known as a nonsense mutation. The gene cannot make a full, working protein to control movement of salt and water in and out of cells, resulting in a thick, sticky mucus in lungs and intestines. CF patients suffer chronic breathing difficulty, gut discomforts, exhaustion, and infections requiring antibiotics and hospitalization. The disease affects more than 40,000 people in the United States and 105,000 people worldwide.

Moving forward from successful safety and efficacy studies in mice and CF patient cells, Dr. Li and his team are working to produce a safe, effective inhalable spray. They’re also investigating using the novel LNP/tRNA platform to treat other diseases.

“Only three types of stop codons cause nonsense mutations, but they’re implicated in thousands of different genetic disorders affecting the lungs, liver, eyes, brain, and muscles,” Dr. Li says. “Lipid nanoparticles can be precisely engineered, so theoretically, we could load tRNAs that recognize each of these stop codons to restore protein production across many of these conditions.”

“Our goal is to provide safe, effective, and lasting relief for cystic fibrosis patients who lack therapeutic options.”