New techniques for transforming RNA molecules into circular forms may lead to improved and longer-lasting treatments, according to a recent study. This breakthrough could benefit a variety of diseases, providing a more sustainable option compared to current RNA therapies, which often have limited efficacy in the body.
Researchers at the University of California San Diego have introduced new techniques to form RNA molecules into circular shapes, which could pave the way for more effective and prolonged therapies. This innovation shows potential for numerous diseases and presents a more persistent alternative to existing RNA therapies, which generally face challenges due to their ephemeral effectiveness in the body.
The findings were published on August 26 in Nature Biomedical Engineering.
RNA molecules have become essential tools in contemporary medicine. They can silence specific genes with small interfering RNAs (siRNAs) or act as blueprints for creating therapeutic proteins, as seen with messenger RNAs (mRNAs). Unlike gene editing methods, which permanently alter DNA, RNA therapies provide a temporary yet highly targeted solution.
Nevertheless, a significant obstacle is that RNAs usually do not persist long in the body, which hampers their effectiveness. Circular RNAs (cRNAs) have emerged as a potential answer to this issue. Unlike linear RNAs, circular RNAs have a closed-loop structure that makes them more resilient to breakdown. However, existing techniques for generating circular RNAs have been complicated and ineffective.
To address these challenges, a research team led by Prashant Mali, a professor at UC San Diego’s Shu Chien-Gene Lay Department of Bioengineering, created two innovative and scalable methods for producing circular RNAs. One method utilizes a natural protein called RtcB within cells to splice RNA strands into loops. The second method employs a specific bacterial enzyme known as group II introns to create circular RNAs outside of cells. The team also developed straightforward purification processes that significantly enhance the yield of circular RNAs. These advancements enable the production of circular RNAs in greater quantities and with much greater ease than before.
The produced circular RNAs were evaluated in heart muscle cells and neurons, showing improved stability and biological activity, surpassing traditional linear RNAs in both cell types. These results indicate that circular RNAs may be advantageous in treating disorders affecting the heart and nervous system.
Moving forward, researchers aim to broaden these studies into more in vivo environments.