Circio Partners with Avenue Biosciences to Boost Secreted Proteins in AAV Therapies
The companies have entered into a research collaboration to optimize secretion of therapeutic proteins targeting improved durability and efficiency of adeno-associated virus (AAV)-delivered gene medicines.
Norwegian biotechnology company, Circio, and protein engineering experts, Avenue Biosciences, have announced a research collaboration to combine their respective technologies to improve the long-term expression of secreted proteins for treatment across a broad range of diseases (1). Through the collaboration, the partners are aiming to determine whether combining durable circular RNA expression with optimized signal peptides can act synergistically to increase secreted protein output per dose in AAV gene therapy settings.
Circio is developing circVec, a circular RNA-based expression platform designed to drive higher and more durable protein production from gene and cell therapy vectors. Company data suggests that circVec achieves longer RNA half-life and substantially increased protein expression compared with conventional mRNA-based viral and non-viral vector systems.
Avenue Biosciences has built a high-throughput protein engineering platform that combines wet lab chemistry with machine learning to optimize signal peptides that direct proteins into the secretory pathway. By screening thousands of signal peptide–protein combinations, the company seeks to boost the amount of protein that is correctly processed and released from cells to overcome the production bottlenecks that can limit biologics development.
Initial work will involve Avenue Biosciences using its platform to identify signal peptides that improve secretion of therapeutic proteins encoded by Circio’s circVec constructs. The first wave of screening work will be performed by Avenue, after which Circio will perform follow-up in vitro and in vivo studies to validate the most promising candidates and assess their performance in relevant disease models. If successful, this approach could help address common limitations of gene therapies, such as the need for high vector doses and associated manufacturing complexity and cost, by improving the efficiency of protein production from each delivered construct.
“Many gene therapies are limited by insufficient protein expression, driving high doses, manufacturing complexity, and cost. The secretory pathway — the cellular machinery that produces and exports proteins — is a largely underutilized engineering opportunity,” said Tero-Pekka Alastalo, MD, PhD, CEO, Avenue Biosciences, in a company press release (1). “By combining Circio's durable circular RNA expression with our technology, we aim to increase protein output per dose and ultimately help more patients benefit from life-changing genetic medicines.”
“A significant proportion of therapeutically relevant payloads for circVec are secreted proteins,” added Dr. Victor Levitsky, CSO of Circio, in the press release (1). “With the Avenue platform, we will test how signal peptide optimization can enhance secretion of proteins and thereby open novel opportunities for the circVec platform in genetic and chronic disease. This collaboration is an important addition to our pre-clinical development strategy of testing circVec in multiple settings through R&D partnerships to broadly explore the range of therapeutic options available for our unique circular RNA expression technology.”
Circio positions the collaboration as a strategic extension of its preclinical program to test circVec across multiple tissues and genetic payloads via R&D partnerships. A significant share of the company’s target payloads are secreted proteins, making secretion optimization a priority for unlocking new indications in both genetic and chronic disease. Avenue Biosciences sees the alliance as aligned with its mission to ensure that potentially life-saving protein therapeutics are not held back by manufacturing constraints.
Reference
Circio. Circio and Avenue Biosciences Jointly Announce Research Collaboration to Enhance Protein Secretion for Gene Therapy. Press Release, July 16, 2026.