Circular RNA: A Leap Toward Effective Treatments

New techniques for shaping RNA molecules into circular forms could lead to more effective and long-lasting treatments, according to a study by researchers at the University of California San Diego. This breakthrough could enhance the durability of RNA therapies, which currently often have limited effectiveness due to their short lifespan in the body.

The study, published in Nature Biomedical Engineering, explores how circular RNA (cRNA) molecules could offer a more enduring solution compared to traditional RNA therapies. While linear RNAs are used for gene silencing through small interfering RNAs (siRNAs) or to produce therapeutic proteins like messenger RNAs (mRNAs), they typically degrade quickly, reducing their therapeutic potential.

Circular RNAs, with their closed-loop structure, are more resistant to degradation than their linear counterparts. However, creating these circular forms has traditionally been complex and inefficient. Researchers led by Prashant Mali, a professor in the Shu Chien-Gene Lay Department of Bioengineering at UC San Diego, have developed two innovative methods to produce circular RNAs more easily and on a larger scale. One method utilizes a natural protein called RtcB inside cells to form RNA loops, while the other uses a bacterial enzyme known as group II introns to create circular RNAs outside of cells.

The team also designed straightforward purification steps that significantly increase the yield of circular RNAs. These advancements allow for the production of circular RNAs in greater quantities and with higher efficiency than before.

Tests conducted on heart muscle cells and neurons demonstrated that circular RNAs exhibited greater stability and biological activity compared to traditional linear RNAs. These promising results indicate that circular RNAs could be particularly useful for treating heart and nervous system conditions.

The researchers are now focused on expanding their studies to include additional in vivo applications.