Circio Introduces circVec 3.0 and Circular mRNA That Lasts 75 Times Longer Than Linear mRNA

Circio Holding ASA, a biotechnology company specialising in advanced circular RNA technology for next-generation nucleic acid medicine, has shared an exciting R&D update. The company unveiled its latest circVec 3.0 circular mRNA expression system and presented bioinformatic analysis of long-term expression data in mouse muscle. The results show that circular mRNA achieved a prolonged half-life of up to 75 times longer than linear mRNA in vivo.

Dr. Thomas B Hansen, CTO at Circio, said in a statement, “With Circio´s circVec 2.1 construct, we have already demonstrated the potential of our powerful circular RNA technology to outperform mRNA-based expression systems both in vitro and in vivo. Continued optimisation of the circVec genetic cassette has now resulted in the discovery of a novel enhancer element, which brings up to 27- and 4-fold improvement over the previous circVec 1.1 and 2.1 generations, respectively. This new component will be added as a standard design feature in circVec generation 3.0.”

He further added, “We are very eager to explore how this new feature can further boost circVec protein expression level and durability in vivo, with the aim to improve potency and safety of nucleic acid medicines. Our science team is now rapidly advancing to implement the new circVec 3.0 design into AAV and DNA-based vector formats for future therapeutic applications.”

Circio also shared bioinformatic analysis of long-term in vivo data, revealing that circular mRNA has an estimated half-life of over 600 hours compared to less than 10 hours for linear mRNA in mouse muscle. This represents up to 75 times longer durability in vivo, a significant improvement over the 15-fold enhancement observed in earlier in vitro studies.

Dr. Erik Digman Wiklund, CEO at Circio, mentioned, “Reaching this level of unprecedented RNA half-life in vivo, combined with the added power of circVec generation 3.0, represents the latest major milestone for our circular mRNA expression platform. We are demonstrating that our technology has the potential to substantially enhance current gold-standard nucleic acid medicines and bring benefit to patients with difficult-to-treat diseases for which there are no cures available today.”

Circio has provided interim results for its AAV gene therapy vector format. Initial tests with an AAV9 construct using the circVec 2.0 genetic cassette showed protein expression similar to the current gold-standard mRNA-AAV during the first 30 days after systemic administration in vivo. The ongoing experiment is anticipated to show the circVec expression advantage starting around 4 weeks post-injection, with further increases over time. Meanwhile, the company is developing circVec 3.0 AAV constructs, which are set to begin in vivo testing in the first quarter of 2025.

Circio will present and discuss the circVec 3.0 data and recent in vivo results during a live webcast on December 4, 2024, at 10:00 AM CEST. A recording of the session will be available later on the Circio website.