A Breakthrough in RNA Therapy for Heart and Nervous System Diseases

Researchers at the University of California San Diego have developed new techniques to sculpt RNA molecules into circles that may result in more potent and long-lasting treatments. This development is promising for several illnesses and provides a longer-lasting substitute for current RNA therapeutics, which frequently have short half-lives in the body.

The research was published in the journal Nature Biomedical Engineering.

RNA molecules are now highly useful instruments in contemporary medicine. They can function as templates for the synthesis of therapeutic proteins, as demonstrated by messenger RNAs (mRNAs), or they can silence genes through small interfering RNAs (siRNAs). RNA therapies provide a short-term, highly targeted treatment option in contrast to gene editing technologies, which alter DNA permanently.

One significant issue, though, is that RNAs are not very effective because of how quickly they degrade in the body. Circular RNAs, or cRNAs, are gaining popularity as a potential remedy for this problem. Circular RNAs, with their closed-loop structure, are more resistant to degradation compared to linear RNAs. However, current methods for generating circular RNAs are complex and inefficient.

To overcome these obstacles, scientists under the direction of Prashant Mali, a professor in the UC San Diego Shu Chien-Gene Lay Department of Bioengineering, created two brand-new, easily scaled techniques for creating circular RNAs.

The alternative technique, on the other hand, creates circular RNAs outside of cells using a class of bacterial enzymes called group II introns. Additionally, the researchers created straightforward purification procedures that greatly increase the production of circular RNAs. Circular RNAs may now be made more easily and in larger quantities than was previously feasible because of these developments.

Neurons and heart muscle cells were used to test the circular RNAs. In comparison to conventional linear RNAs, they exhibited improved stability and biological activity in both cell types. These results imply that cardiac and nervous system disorders may benefit from the use of circular RNAs.

Scientists are trying to expand these investigations into other in vivo environments.

Source:
Journal reference:

Tong, M., et al. (2024) 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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