Seoul, South Korea, September 7, 2026
RZNOMICS Inc., a biopharmaceutical company focused on RNA-based gene therapies, has reported major advances in the efficient production of circular RNA (circRNA) through its proprietary Self-Targeting and Splicing (STS) technology. The findings were published online on September 4, 2026, in Nucleic Acids Research, a leading journal covering nucleic acid research and molecular biology. The study, titled “Target Site Selection and P1 Engineering Enable Highly Efficient Circular RNA Production via End-to-End Self-Targeting and Splicing,” describes an optimized approach that improved circularization efficiency by up to approximately seven-fold compared with the company’s original STS design and demonstrated enhanced production of large RNA molecules approaching 8 kilonucleotides.
RZNOMICS Optimizes Circular RNA Production Technology
The study addresses a major technical challenge in the development of circRNA therapeutics: achieving efficient circularization as RNA molecules become longer. Unlike conventional linear RNA, circRNA forms a covalently closed-loop structure that can provide increased resistance to enzymatic degradation. This stability has made circRNA an emerging modality for potential applications including protein replacement therapies, vaccines and other RNA-based medicines. However, circularization efficiency can decline as RNA length increases, potentially limiting the size and complexity of therapeutic sequences that can be incorporated into circRNA constructs. To address this limitation, the RZNOMICS research team systematically evaluated different target sites within RNA sequences to determine how their positions influenced the self-circularization reaction. The researchers found substantial differences in circularization efficiency depending on target-site location, even when working with the same RNA sequence. This finding identified target-site selection as an important variable for improving circRNA production. The team subsequently combined optimized target-site selection with engineering of the P1 construct, a component involved in the company’s STS-mediated self-circularization process, to further enhance production efficiency.
Engineered STS Technology Improves Large RNA Circularization
The researchers further modified the P1 construct by sequentially introducing a short polyA10 sequence and an antisense sequence designed to strengthen interaction with the selected target site. According to the study, these modifications increased self-circularization efficiency by approximately seven-fold compared with the original STS configuration. The improvement is particularly relevant because efficient production of larger circRNA molecules remains an important challenge for the field, especially when therapeutic applications require the expression of relatively large proteins. In experiments involving Factor VIII RNA approximately 7.8 kilonucleotides in length, the optimized STS method achieved approximately two-fold higher circularization efficiency than the widely used Permuted Intron–Exon (PIE) method. Factor VIII is a large protein involved in blood coagulation, making its RNA a useful model for evaluating the ability of a circularization platform to accommodate relatively long therapeutic sequences. The findings suggest that combining rational target-site selection and P1 engineering can improve circRNA production across both shorter and larger RNA molecules.
Advertisement
Platform Could Expand CircRNA Therapeutic Applications
The reported advances could strengthen RZNOMICS’ broader circRNA platform by addressing a manufacturing and molecular-engineering constraint that may affect the scalability and applicability of circular RNA technologies. According to the company, the optimized STS approach could provide a broadly applicable method for producing circRNA with improved efficiency, including RNA molecules approaching 8 kilonucleotides. More efficient circularization could potentially support the development of therapeutic constructs requiring larger coding sequences while improving the practicality of circRNA production. RZNOMICS said it plans to expand the utility of its proprietary circRNA technology across diverse therapeutic applications, including CAR-T therapies. The company’s research represents an early-stage technology development rather than evidence of clinical efficacy or regulatory approval. Further studies will be required to evaluate manufacturing scalability, product quality, biological performance, durability and therapeutic safety. Nevertheless, the publication in Nucleic Acids Research provides peer-reviewed evidence supporting the potential of STS technology for high-efficiency circRNA production and highlights the growing importance of RNA engineering platforms in next-generation biopharmaceutical development.
Source: RZNOMICS press release
