Advancements in Gene Editing Techniques

In a significant step towards improving gene editing technologies, scientists at the University of Texas at Austin have developed a more precise and efficient approach that can correct multiple disease-causing mutations in mammalian cells simultaneously. This new technique has also been successful in repairing mutations associated with scoliosis in fish embryos.

Using Retrons to Enhance Gene Editing

Retrons are genetic elements originally found in bacteria that help them defend against viral infections. Now, for the first time, researchers have used retrons to correct a disease-related mutation in vertebrates, opening new avenues for developing genetic therapies for human diseases.

Jesse Buffington, a graduate student at the University of Texas and one of the authors of the new paper in the journal “Nature Biotechnology,” stated: “Many current gene editing methods are limited to one or two mutations, leaving many people behind. My hope, and what drives me, is to develop a gene editing technology that is more inclusive for people who may have unique disease-causing mutations, and that using retrons can expand this impact to a broader range of patients.”

Replacing Damaged DNA with Healthy Strands

The retron-based system can replace long segments of damaged DNA with healthy ones. This means that a single retron package can correct multiple mutations within the same stretch of DNA, rather than targeting a specific defect each time.

Eliah Finkelstein, a professor of molecular biology at the University of Texas, said: “We want to democratize gene therapy by creating ready-made tools that can treat a large group of patients at once.”

While retrons have been used in mammalian cells before, previous attempts were highly inefficient, correcting only about 1.5% of targeted cells. However, the University of Texas team’s method significantly improved this efficiency, successfully introducing healthy DNA into about 30% of targeted cells. Researchers believe they can further increase this number as the technology evolves.

Applying the Technique to Cystic Fibrosis

The research team is now adapting their approach to treat cystic fibrosis (CF), a life-threatening disorder caused by mutations in the CFTR gene. These mutations lead to the accumulation of thick mucus in the lungs, causing chronic infections and long-term lung damage.

The University of Texas recently received a grant from Emily’s Entourage, a nonprofit organization dedicated to finding treatments for people who do not benefit from current therapies. Researchers have begun working on replacing the damaged regions of the CFTR gene in laboratory models that mimic cystic fibrosis symptoms, and later in patient-derived lung cells.

Buffington noted: “Traditional gene editing techniques work best with single mutations and are costly to refine, so gene therapies tend to focus on the most common mutations. But there are over a thousand mutations that can cause cystic fibrosis. It is not economically feasible for companies to develop a gene therapy for just three people.”

Conclusion

This work represents an important step towards more adaptive, efficient, and inclusive genetic therapies for patients facing complex genetic diseases. By using retrons, gene editing efficiency can be improved, and the scope of benefit can be expanded to include a larger number of patients with unique or rare mutations. As research and developments continue, we may witness a brighter future in the field of genetic therapies.