On October 26, 2023 Circio reported 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 (Press release, Circio, OCT 26, 2023, View Source [SID1234636337]). 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.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
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