Genetic information within our cells is managed by ribonucleic acid, or RNA. For years, scientists focused on linear RNA, which has distinct beginning and end points. However, circular RNA (circRNA) has emerged as a significant area of scientific exploration. Unlike linear RNA, circRNA forms a closed loop, providing it with unique characteristics. This structure is opening new avenues for understanding cellular processes and developing innovative treatments.
What Makes Circular RNAs Unique?
Circular RNAs have a closed-loop structure, lacking the typical ends found in linear RNA. This configuration provides stability, making them resistant to degradation by enzymes. Biologically, circRNAs form through a process called backsplicing, where sections of pre-messenger RNA (pre-mRNA) are joined.
Within cells, naturally occurring circRNAs perform various functions. Many act as “sponges” for microRNAs (miRNAs), binding to these small regulatory RNAs and preventing them from silencing target genes. This fine-tunes gene expression. Some circRNAs also interact with specific proteins, influencing their activity or location, while others serve as templates for protein production.
Why Circular RNAs Offer New Hope
The stability of circular RNAs provides advantages over traditional linear RNA therapies, such as messenger RNA (mRNA). Because they are less prone to enzymatic breakdown, circRNAs exhibit a longer half-life within the body, persisting for extended periods. This prolonged presence could lead to more sustained therapeutic effects, potentially reducing the frequency of dosing.
The absence of free ends in circular RNA may also contribute to reduced immunogenicity, meaning they are less likely to trigger an unwanted immune response compared to linear RNA. The immune system can sometimes recognize the ends of linear RNA as foreign, leading to inflammation. This lower potential for immune activation could make circRNAs safer and more tolerable for patients over long-term treatment. Their ability to serve as templates for protein production also makes them candidates for therapies requiring continuous delivery of a therapeutic protein.
How Circular RNAs Are Being Used in Medicine
Circular RNAs are being explored across various therapeutic applications, leveraging their properties to address diseases.
Vaccine Development
CircRNAs can be engineered to encode specific antigens, which the body then produces to elicit a robust and lasting immune response. This approach holds promise for developing more stable and potent vaccines against infectious diseases, potentially offering advantages in storage and distribution.
Gene Therapy
Circular RNAs are investigated as vehicles for delivering therapeutic proteins or correcting genetic defects. They can be designed to produce specific proteins missing or dysfunctional in genetic disorders, offering a sustained supply. Research also explores their use in delivering components for gene editing, allowing for precise and lasting genetic modifications within target cells.
Other Diseases
Beyond vaccines and gene therapy, circRNAs show promise as therapeutic agents or biomarkers in various complex diseases. In cancer research, they are studied for their potential to regulate genes involved in tumor growth or suppression, or as diagnostic indicators. They are also explored in cardiovascular diseases to modulate gene expression related to heart function and repair, and in neurological disorders to deliver neuroprotective factors or regulate pathways implicated in conditions like Alzheimer’s or Parkinson’s diseases.
The Path Ahead for Circular RNA Therapeutics
The field of circular RNA therapeutics is advancing, with much research in preclinical stages, involving laboratory and animal studies. Early-stage clinical trials are beginning to emerge, indicating a transition towards human testing. Researchers are working to overcome several challenges to bring these therapies to widespread clinical use.
One hurdle involves developing efficient and targeted delivery methods to ensure synthetic circRNAs reach specific cells or tissues, minimizing off-target effects. Various delivery systems, including lipid nanoparticles and modified viral vectors, are under investigation. Another focus is optimizing large-scale manufacturing processes to produce high-purity circRNAs consistently and cost-effectively. Further understanding of the biological mechanisms underlying both natural and engineered circRNAs will also refine their therapeutic design and application.