New methods to shape RNA molecules into circles could lead to more effective and long-lasting therapies, shows a study by researchers at the University of California San Diego.
University of California - San DiegoAug 27 2024 The advance holds promise for a range of diseases, offering a more enduring alternative to existing RNA therapies, which often suffer from short-lived effectiveness in the body. RNA molecules have emerged as powerful tools in modern medicine. They can silence genes through small interfering RNAs or serve as templates for making therapeutic proteins, as seen with messenger RNAs .
However, one major challenge is RNAs do not last long in the body, which limits their effectiveness. The concept of circular RNAs have gained traction as a solution to this challenge. Circular RNAs, unlike their linear counterparts, have a closed-loop structure that renders them more resistant to degradation. The problem is that existing methods for creating circular RNAs are complex and inefficient.
To overcome these hurdles, researchers led by Prashant Mali, a professor in the Shu Chien-Gene Lay Department of Bioengineering at UC San Diego, developed two new methods for producing circular RNAs that are simple and scalable. One method occurs inside cells using a naturally occurring protein called RtcB, to splice RNA strands into loops. The other method, in contrast, uses a type of bacterial enzyme known as group II introns to form circular RNAs outside of cells.
The circular RNAs were tested in heart muscle cells and neurons. They displayed enhanced stability and biological activity, outperforming traditional linear RNAs in both cell types. These findings suggest that circular RNAs could be beneficial in treating conditions that affect the heart and nervous system.Source:University of California - San Diego
Journal reference:Tong, M., et al. . Robust genome and cell engineering via in vitro and in situ circularized RNAs. Nature Biomedical Engineering. doi.org/10.1038/s41551-024-01245-z.
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