Algonomics Develops Foundational Technology to Boost Circular RNA Production Efficiency by Up to Sevenfold

Optimization of Self-Circularization Structures

"Expanded Applications Anticipated in RNA Therapeutics, Vaccines, and CAR-T Cell Therapies"

Algonomics, a company specializing in the development of RNA-based gene therapies, announced on September 7 that it has developed a technology that increases the production efficiency of circular RNA by up to sevenfold.

Circular RNA features a structure in which the ends of the RNA are connected, making it more resistant to degradation compared to linear RNA. As a result, circular RNA is gaining attention for its potential use in RNA therapeutics and vaccines. However, as the length of the RNA increases, the efficiency of circularization decreases, which has limited the range of applicable genes and large-scale production.

Algonomics company logo image. Algonomics

The research team improved Algonomics's STS (Self-Targeting and Splicing) technology, which enables RNA to form a circular structure spontaneously during in vitro transcription. By selecting optimal target sites for circularization and optimizing the ‘P1 structure’ involved in the process, they enhanced production efficiency. They found that even with the same RNA sequence, differences in the location of target sites led to variations in circularization efficiency, confirming that selecting the optimal target site is a key factor for high-efficiency production.

For the P1 structure, the team sequentially applied a short polyA10 sequence and antisense sequences to strengthen the binding with the target site. As a result, circular RNA production efficiency improved by up to seven times compared to previous approaches. Notably, when the optimized STS technology was applied to Factor VIII RNA, which is about 7,800 bases in length, the circularization efficiency was about twice as high as the conventional PIE (Permuted Intron-Exon) method.

The researchers explained that their results demonstrate the capability to produce circular RNA efficiently not only for short RNA but also for long RNA strands of up to roughly 8,000 bases. Algonomics plans to leverage this technology as a platform for developing circular RNA-based therapies and vaccines.

Kyung-Hyun Lee, principal researcher at Algonomics and first and co-corresponding author of the study, stated, “We have established a foundation for stable and highly efficient production of circular RNA even for long RNA molecules,” adding, “This will enable us to expand the application scope of circular RNA moving forward.” Co-corresponding author and Algonomics CEO Sungwook Lee said, “This research has further validated the practical potential of circular RNA platform technology,” and added, “We plan to extend its use into a wide range of therapeutic areas, including CAR-T cell therapies.” The findings of this study were published online on September 4 in the international journal Nucleic Acids Research (NAR), which covers nucleic acid and molecular biology research.

This content was produced with the assistance of AI translation services.