• AAV-circVec 3.2 achieves 40-fold enhanced protein expression in heart vs. conventional mRNA-based AAV gene delivery
• Results are highly statistically significant and have been confirmed both by longitudinal live imaging and ex vivo tissue analyses
• Similar results from ongoing experiments targeting other tissues with different AAV variants support broad applicability of the circVec technology as a novel platform to transform gene therapy
• Circio has selected Danon disease as the initial cardiac indication to validate the AAV-circVec technology in a therapeutic setting

 
Oslo, Norway 8 October 2025 – Circio Holding ASA (OSE: CRNA), a biotechnology company developing powerful circular RNA technology for next generation nucleic acid medicine, today announces the publication of a comprehensive data package demonstrating AAV-circVec in vivo tissue-specific proof-of-concept. The results are being delivered in a poster presentation at the European Society of Cell and Gene Therapy (ESGCT) annual meeting 2025 in Seville, Spain.
 
In the ESGCT poster presentation, Circio is presenting new and expanded in vivo results demonstrating the advantage of circVec as a novel expression system to transform AAV gene therapy. In heart tissue, circVec 3.2 shows highly localized activity that outperforms conventional mRNA-based AAV expression by up to 40-fold. These results have been demonstrated and confirmed both by IVIS scanning and post-mortem ex vivo tissue analysis. To validate the technology in a therapeutically relevant setting, Circio has initiated technical development of circVec-AAV gene therapy constructs for Danon disease, a devastating cardiac genetic disease with no therapeutic options available today.
 
“Circio has worked systematically to optimize the circVec design for AAV gene delivery over the past two years. The latest circVec 3.2 generation incorporates a novel genetic feature that drives up AAV protein expression to levels that substantially exceed conventional mRNA-based AAVs. We are now advancing rapidly to validate these findings in relevant genetic disease models,” said Dr. Thomas B. Hansen, CTO of Circio. “Importantly, the strong advantage in the heart is also observed in several other tissues and AAV variants. This consistency supports broad applicability of our circVec platform, thereby opening development and partnering opportunities in multiple therapeutic areas.”
 
The presentation also includes data showing a strong increase in expression levels with the trend for continued signal accumulation following local delivery of previous generation circVec 2.0 AAV vector to the eye. Testing of the latest generation circVec 3.2 in eye and other tissues is currently being initiated, and a novel circVec generation 4.0, which incorporates further genetic enhancer elements, is due to enter initial in vivo screening experiments.
   
“ESGCT provides an excellent forum to showcase the circVec platform to a wide academic and industry audience as a potential solution to address the key issue preventing broad adoption and success of AAV gene therapy,” said Dr. Erik D Wiklund, CEO of Circio. “The AAV field has recently experienced several major setbacks due to severe toxicity issues in ongoing clinical studies. Switching to circVec-based expression can enable substantial dose reduction, which we expect will lead to considerable improvements in safety for patients and lower treatment cost. The circVec platform could thereby completely transform the clinical and commercial viability of AAV therapy as we know it today and establish circVec as a novel gold-standard gene expression system.”
 
 
 
Title of presentation and poster:
CircVec: Enhancing gene and cell therapy using circular RNA vector expression technology (poster no. 1041)

Presenter: CTO Dr. Thomas B Hansen & CSO Dr. Victor Levitsky