New Data Demonstrates Unique Expression Profile of RNA Platform
Circio presented the enhanced in vivo data for its circVec platform in viral and non-viral vectors at ASGCT 2025.
Norwegian biotechnology company, Circio Holding ASA, has presented expression data for both viral and non-viral vector formats for its new and strengthened circVec vectors at the American Society of Gene and Cell Therapy (ASGCT) annual meeting 2025 in New Orleans, USA (1). Showcasing its latest in vitro and in vivo results for its circVec platform, the company demonstrated the platform’s broad capability to significantly boost protein expression level and durability for both viral and non-viral gene and cell therapy.
The new data show that both viral and non-viral circVec vectors exhibit tissue distribution patterns that differ markedly from those of comparable messenger RNA (mRNA) vectors — specifically, circVec drives higher protein expression in the muscles, heart, and spleen, while maintaining consistently low expression in the liver. Although unexpected findings, they point to a fundamental biological distinction between circRNA- and mRNA-based expression systems to offer potential advantages of the circVec platform in therapeutic areas compared to traditional gene therapies.
“Circio is rapidly expanding the in vivo circVec data package, with several recent intriguing advances. It has become evident that circVec not only offers increased protein expression level and durability in general, but also that this effect is associated with a distinct tissue profile,” said Dr. Thomas B. Hansen, CTO of Circio, in a May 14, 2025 company press release about the data (1).
Further to the announcement, Circio is currently working on the development of its own circVec-adeno-associated virus (AAV) gene therapy programs targeting muscular dystrophies and cardiomyopathies. In vivodata over a six-month period has indicated a consistent advantage of circVec in achieving robust expression at low doses, notably showing enhanced expression in target tissues alongside reduced liver accumulation, suggesting a more pronounced benefit in select tissues and therapeutic contexts (1).
These findings are particularly significant in the broader context of gene and cell therapy, where the choice of delivery vector vary depending on the affected tissue, the level of gene expression, and the required duration of expression (2). Viral vectors — notably AAVs — are widely used due to their high transduction efficiency and long-term expression. However, they face well-documented limitations, including immunogenicity and limited cargo capacity, with a strong tropism for the liver, which can lead to off-target effects and safety concerns in systemic delivery (3). Non-viral delivery systems, while generally safer, more scalable and efficient, and widely customizable, are limited by their clinical applicability (4).
The ability of circVec to enhance and prolong protein expression in both viral and non-viral formats combined with the distinct tissue expression profile — enhanced expression in muscle, the heart, and the spleen, and reduced liver accumulation — could address a critical gap in targeting extrahepatic tissues with minimal off-target toxicity. These results reinforce the potential of circVec as an expression platform that could overcome several key challenges associated with current gene therapy modalities to enable more targeted and safer therapeutic strategies.
References
Circio. Circular RNA innovator Circio presents strengthened circVec gene therapy data at ASGCT 2025. Press Release, May 13, 2025.
Bulcha, J.T.; Wang, Y.; Ma, H.; Tai, P.W.L.; Gao, G. Viral Vector Platforms Within the Gene Therapy Landscape. Sig. Transduct. Target. Ther., 2021, 6, 53.
Wang, D.; Tai, P.W.L.; Gao, G. Adeno-Associated Virus Vector as a Platform for Gene Therapy Delivery. Nat. Rev. Drug Discov., 2019, 18, 358–378.
Cavazza, A.; Molina-Estévez, F.J.; Reyes, A.P.; et al. Advanced Delivery Systems for Gene Editing: A Comprehensive Review from the GenE-HumDi COST Action Working Group. Mol. Ther. Nucleic Acids, 2025, 36 (1), 102457.