- New circVec 2.0 design boosts protein expression by up to 10-fold vs. circVec 1.0
- Bioinformatic simulation indicates 10-30-fold higher maximum protein expression vs. mRNA-based systems
- circVec has the potential to replace mRNA as the preferred expression system for all viral and DNA-based therapeutics in the future
Circio established the first generation circVec 1.0 genetic cassette based on “Nature´s best design” for human circRNA expression. Following rational, targeted optimization of specific sequences and regulatory elements, Circio has been able to further improve the circRNA biogenesis and translation rate, resulting in up to 10-fold increase in protein payload expression. To Circio´s knowledge, circVec 2.0 far exceeds any other known intra-cellular circRNA expression system, both in terms of circRNA biogenesis efficiency and protein yield.
Thomas Birkballe Hansen, VP and head of Research at Circio said: “We are continuing to evolve our circVec platform, and the enhanced 2.0 design drives potent and persistent protein expression. Durability and toxicity are major issues facing today´s gold-standard gene therapy approaches, which we believe can be overcome by switching from current mRNA-based expression to our circVec system. We have not reached the full potential of our technology yet, and we are continuously exploring further optimization strategies towards circVec 3.0 and beyond.”
The data presented at ESGCT 2023 demonstrates the importance of optimizing both the DNA genetic cassette and the circRNA design to maximize protein payload expression. By modifying the flanking inverted repeat elements (IR), circRNA biogenesis was improved by 2-3 -fold vs. circVec 1.0. Screening and selecting novel internal ribosome entry site (IRES) elements increased the protein translation rate by 2-6 -fold. Combining these modifications, the resulting protein payload expression was enhanced by 3-10-fold vs. circVec 1.0 (depending on cell type), and outcompeted mRNA already at early time points.
Furthermore, bioinformatic modelling of long-term dynamics, based on Circio´s experimental results and externally published data, showed substantially elevated and more durable expression levels from circRNA compared to conventional mRNA vectors. This characteristic can enable improved therapeutic potency, lower dosing, and reduced toxicity. As such, circRNA is expected to replace mRNA as the preferred expression system for all viral and DNA-based therapeutics in the future.
Please see the poster here: 2023 ESGCT poster
For further information, please contact:
Erik Digman Wiklund, CEO
Phone: +47 413 33 536
Renate Birkeli, Investor Relations
Phone: +47 922 61 624
Building next generation RNA therapeutics
Circio Holding ASA (OSE: CRNA) is a biotechnology company developing novel circular RNA and immunotherapy medicines.
Circio has established a unique circular RNA (circRNA) platform to develop novel circRNA medicines for rare disease, vaccines, and cancer. The proprietary circVec technology is based on a modular genetic cassette design for efficient biogenesis of multifunctional circRNA from DNA and viral vectors, which can be deployed for many purposes. The circVec platform has demonstrated enhanced and more durable protein expression than classic mRNA vector systems, and has the potential to become the new gold-standard for DNA and virus-based therapeutics in the future. The circRNA R&D activities are being conducted by the wholly owned subsidiary Circio AB based at the Karolinska Institute in Stockholm, Sweden.
In addition, Circio is developing a cancer vaccine, TG01, targeting KRAS driver mutations. TG01 is currently being tested in two clinical trials in RAS-mutated pancreatic cancer and multiple myeloma in the USA and Norway. These studies are being run through academic collaborative networks, supported by prestigious research grants from Innovation Norway and the Norwegian Research Council, creating read-outs and future optionality for the program at low cost to Circio.