Novel Gene Editing Technique offers Hope for Broad Range of Genetic Diseases
Researchers at the University of Texas at Austin have developed a new gene editing platform utilizing bacterial retrons that demonstrates the potential to correct multiple DNA mutations simultaneously, offering a significant advancement over current gene therapy approaches. Published in Nature Biotechnology, the study details a system capable of replacing extended stretches of damaged DNA with healthy sequences, perhaps benefiting patients with rare genetic diseases currently excluded from existing treatments.
Current gene editing methods, like CRISPR, often target single mutations, making them impractical and costly to adapt for the vast array of genetic variations that cause disease. this limitation leaves many patients with rarer forms of genetic conditions without viable therapeutic options. The UT Austin team’s retron-based system bypasses this issue by repairing entire genomic segments rather than individual mutations. This allows a single intervention to address diverse mutations within the same region, eliminating the need for personalized adaptations for each patient’s genetic profile.
Previous attempts to implement retron technology in mammalian cells yielded low efficiency, successfully introducing new DNA into only approximately 1.5% of target cells. The new method significantly improves upon this, achieving a success rate of around 30% – a substantial increase the researchers believe can be further optimized. Furthermore, the retron system can be delivered as RNA encapsulated in lipid nanoparticles, addressing delivery challenges associated with many conventional gene editing tools.
The team is currently applying this technology to cystic fibrosis,a disease characterized by over a thousand potential causative mutations in the CFTR gene. A grant from Emily’s Entourage, a non-profit focused on the 10% of cystic fibrosis patients unresponsive to existing therapies, is supporting research into rare CFTR variants. Researchers have begun replacing defective regions of the CFTR gene in disease-modeling cell lines and plan to extend their studies to airway cells directly obtained from patients.
Additional funding from the Cystic Fibrosis Foundation will support research focused on the region of the CFTR gene containing the most common disease-causing mutations. The advancement of standardized,”off-the-shelf” gene therapies based on this platform could also streamline the regulatory approval process,requiring only a single approval for a broader patient population. The research was funded by Retronix Bio and the Welch Foundation.
