Could circular RNAs revolutionize treatments for cancer and infectious diseases?
Linear messenger RNA molecules, used in Covid-19 vaccines, marked a turning point in modern medicine. However, their fragility in the face of enzymes and their ability to trigger undesirable immune reactions still limit their large-scale use. A promising alternative is emerging today: circular RNAs. These loop-shaped molecules are more resistant to degradation and cause fewer immune reactions. They could thus offer more stable and longer-lasting treatments for diseases such as cancer, viral infections, or metabolic disorders.
Circular RNAs stand out due to their unique structure. Unlike linear RNAs, they have neither a beginning nor an end, which protects them from the enzymes that typically break down RNA in the body. This characteristic gives them a much longer lifespan, sometimes more than twice that of classical messenger RNAs. Additionally, they can play multiple roles in cells: some act as microRNA sponges, thereby regulating gene expression, while others interact with proteins or produce small functional proteins themselves.
Recent advances now allow circular RNAs to be manufactured in the laboratory. Scientists are optimizing their production to improve their purity and efficacy. For example, advanced purification techniques eliminate residual linear RNAs, thereby reducing the risk of unwanted immune reactions. These synthetic RNAs can then be encapsulated in lipid nanoparticles or viral vectors for precise delivery to target cells. Once inside the cell, they maintain prolonged production of therapeutic proteins, which is particularly useful for vaccines or cancer therapies.
In the field of oncology, circular RNAs show remarkable potential. They can be designed to encode proteins that stimulate the immune system against tumors. Studies have demonstrated their ability to induce powerful and lasting immune responses, superior to those obtained with traditional messenger RNAs. For instance, circular RNA vaccines against SARS-CoV-2 have generated higher and more persistent levels of neutralizing antibodies compared to messenger RNA vaccines. Similarly, in lung cancer models, circular RNAs encoding cytokines have significantly reduced tumor size.
Their stability is another major advantage. Circular RNAs maintain their integrity for months at moderate temperatures, unlike messenger RNAs, which often require storage at very low temperatures. This characteristic facilitates their storage and distribution, especially in regions where refrigeration infrastructure is limited.
The applications are not limited to cancer and infections. Research is exploring their use to accelerate the healing of chronic wounds, such as diabetic ulcers, or to treat neurodegenerative diseases. Their ability to cross the blood-brain barrier also opens up prospects for therapies targeting the brain.
Finally, circular RNAs could serve as biomarkers. Their presence in blood or other bodily fluids allows for the early detection of certain diseases or monitoring the progression of treatment. Their non-invasive detection makes them valuable diagnostic tools, particularly for cancer or cardiovascular diseases.
Despite these advances, challenges remain. Large-scale production and complete purification of circular RNAs remain complex. Researchers are also working to improve delivery systems to specifically target diseased tissues without affecting healthy cells. If these obstacles are overcome, circular RNAs could well become the next generation of RNA-based therapies, significantly expanding the possibilities of personalized medicine.
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Official Study Source
DOI: https://doi.org/10.1007/s44258-026-00079-5
Title: Unlocking the potential of engineered circular RNA therapeutics
Journal: Med-X
Publisher: Springer Science and Business Media LLC
Authors: Xueyan Zhen; Mahyar Mahmoudi; Xinrui Lan; Guanheng Huang; Wei Tao