Circio and Solid Biosciences will combine circular RNA and AAV technologies to investigate gene therapy approaches for genetic heart disease.

Combining circular RNA and AAV delivery

Circio Holding and Solid Biosciences have entered a research collaboration to evaluate whether combining Circio’s circVec circular RNA expression platform with Solid’s POLARIS-101 AAV capsid can improve gene delivery to the heart.

The collaboration will investigate whether the combination can increase gene expression in cardiac tissue while reducing the systemic AAV doses required for genetic heart disease therapies.

Current AAV gene therapy approaches for genetic heart conditions can require high doses, which are associated with significant safety risks. Improving the delivery and expression of therapeutic genes could help address these challenges.

Circio’s circVec platform is designed to generate circular RNA inside target cells. Its latest generation 5 construct has demonstrated up to 200-fold enhanced gene expression from AAV vectors in the heart in vivo, according to the company.

Solid’s POLARIS-101 is a proprietary AAV capsid engineered to improve targeting of cardiac and skeletal muscle tissue while reducing liver biodistribution. The company has also reported encouraging early clinical safety data for the technology.

The companies aim to combine the technologies to investigate whether enhanced cardiac targeting and increased gene expression could support more potent gene therapies at lower doses.

Testing the combined gene therapy technology

Under the agreement, Circio will generate circular RNA constructs using its latest generation 5 design. Solid will package these constructs using its POLARIS-101 capsid and dual-plasmid manufacturing platform.

The resulting AAV vectors will be jointly characterised and tested in vitro and in vivo to assess their performance.

If the results are positive, potential therapeutic candidates could progress into further evaluation and preclinical development.

Circio’s chief scientific officer Victor Levitsky said: “Solid Biosciences is at the forefront of AAV engineering, and their engineered capsid, POLARIS-101, has shown impressive cardiac targeting in pre-clinical models, in addition to encouraging clinical safety data.”

He added: “We believe that circVec can build on POLARIS-101’s strong tropism to further amplify cardiac gene expression, potentially enabling next generation heart gene therapies with enhanced potency and specificity.”

Expanding circular RNA applications

The collaboration forms part of Circio’s strategy to evaluate circVec alongside different delivery technologies and explore applications across multiple therapeutic areas.

The company is developing circular RNA expression systems for gene therapy, cell therapy and chronic diseases.

Its circVec platform uses a modular genetic construct designed to generate multifunctional circular RNA inside target cells. Circio reports that the technology has demonstrated up to 75-fold increased RNA half-life and up to 60-fold enhanced protein expression compared with conventional mRNA-based viral and non-viral vector systems.

The company is also investigating applications in eye and central nervous system diseases.

For Solid Biosciences, the collaboration provides an opportunity to explore whether its POLARIS-101 capsid can be combined with circular RNA technology to improve the performance of gene therapies targeting genetic heart conditions.

The research will determine whether the two platforms offer measurable advantages when used together, with further preclinical development dependent on the results.