A study by researchers at the University of California, San Diego, shows that new methods for shaping RNA molecules into circles could lead to more effective and longer-lasting therapies. The breakthrough holds promise for a variety of diseases, as it offers a longer-lasting alternative to existing RNA therapies, which are often short-lived in their effectiveness in the body.
The work was published on August 26 in Biomedical Engineering of Nature.
RNA molecules have emerged as powerful tools in modern medicine. They can silence genes through small interfering RNAs (siRNAs) or serve as templates for making therapeutic proteins, as seen with messenger RNAs (mRNAs). Unlike gene-editing technologies, which make permanent changes to DNA, RNA therapies offer a temporary but highly targeted approach.
However, one of the main challenges is that RNAs do not last long in the body, which limits their effectiveness. The concept of circular RNAs (cRNAs) has gained traction as a solution to this challenge. Circular RNAs, unlike their linear counterparts, have a closed-loop structure that makes them more resistant to degradation. The problem is that existing methods for creating circular RNAs are complex and inefficient.
To overcome these obstacles, researchers led by Prashant Mali, a professor in the Shu Chien-Gene Lay Department of Bioengineering at the University of California, San Diego, developed two new methods for producing circular RNAs that are simple and scalable. One method is carried out inside cells using a naturally occurring protein called RtcB to link RNA strands together into loops. The other method instead uses a type of bacterial enzyme known as group II introns to form circular RNAs outside of cells. The researchers also developed simple purification steps that significantly increase the yield of circular RNAs. These advances mean that circular RNAs can be produced more easily and in larger quantities than previously possible.
The circular RNAs were tested in cardiac muscle cells and neurons. They showed improved stability and biological activity, outperforming traditional linear RNAs in both cell types. These findings suggest that circular RNAs could be beneficial for treating diseases affecting the heart and nervous system.
The researchers are now working to extend these studies to additional in vivo settings.