Researchers at The University of Texas at Austin have created a new gene-editing technique using bacterial retrons that corrects multiple disease-causing mutations simultaneously. This method targets complex genetic disorders like cystic fibrosis and improves efficiency over traditional tools. The breakthrough, published in Nature Biotechnology, offers hope for more inclusive therapies.
Some inherited diseases, such as cystic fibrosis, hemophilia, and Tay-Sachs disease, stem from multiple genetic mutations, complicating broad gene therapies. Scientists at The University of Texas at Austin addressed this by engineering retrons—genetic elements from bacteria that defend against viruses—for precise genome editing in vertebrates. This marks the first use of retrons to correct a disease-related mutation in such organisms, including successful repairs of scoliosis-linked mutations in zebrafish embryos.
The technique replaces large defective DNA sections with healthy sequences, potentially fixing numerous mutations in one go. Unlike existing methods limited to one or two mutations, this approach achieves about 30% efficiency in inserting healthy DNA into target mammalian cells, up from previous retron attempts at 1.5%. Delivery occurs via RNA in lipid nanoparticles, easing integration challenges.
"A lot of the existing gene-editing methods are restricted to one or two mutations, which leaves a lot of people behind," said Jesse Buffington, a graduate student at UT and co-lead author. "My hope... is to develop a gene-editing technology that's much more inclusive." The work, led by Buffington and professor Ilya Finkelstein, received support from Retronix Bio and the Welch Foundation.
Finkelstein added, "We want to democratize gene therapy by creating off-the-shelf tools that can cure a large group of patients in one shot. That should make it more financially viable... and much simpler from a regulatory standpoint because you only need one FDA approval."
The team is adapting the method for cystic fibrosis, caused by CFTR gene mutations leading to lung mucus buildup and infections. A grant from Emily's Entourage targets the 10% of patients unresponsive to current treatments, while Cystic Fibrosis Foundation funding addresses common mutations. Over 1,000 CF mutations exist, and Buffington noted, "With our retron-based approach, we can snip out a whole defective region and replace it with a healthy one, which can impact a much larger part of the CF population."
Co-authors include Hung-Che Kuo, Kuang Hu, You-Chiun Chang, Kamyab Javanmardi, Brittney Voigt, Yi-Ru Li, Mary E. Little, Sravan K. Devanathan, Blerta Xhemalçe, and Ryan S. Gray. The study appears in Nature Biotechnology (2025; DOI: 10.1038/s41587-025-02879-3).