Rznomics cites circRNA production advance

- Rznomics said on September 8 that a Nucleic Acids Research paper reported a higher-efficiency method for producing circular RNA using its self-targeting splicing approach. - The paper said the optimized workflow achieved up to two-fold higher self-circularization efficiency than the conventional permuted intron-exon method for long genes. - The study was published online on September 4, and the authors were affiliated with Rznomics and Dankook University.

Rznomics said on September 8 that a paper in *Nucleic Acids Research* described an updated method for producing circular RNA, or circRNA, with higher efficiency. The study, published online on September 4, focused on manufacturing rather than a clinical result, according to the company and the paper’s PubMed record. The authors said the work optimized “end-to-end self-targeting and splicing,” or STS, a process Rznomics has previously presented as part of its circRNA platform. The paper’s authors were affiliated with Rznomics’ R&D center in Seongnam and Dankook University in Yongin. ### What exactly did the paper report? The paper, titled “Target site selection and P1 engineering enable highly efficient circular RNA production via end-to-end self-targeting and splicing,” said circular RNAs are more stable than linear RNAs and are being explored for vaccines and therapeutics. The authors wrote that their earlier STS method could generate circRNAs without extraneous sequences, but that efficiency fell as the gene of interest became longer. (prnewswire.com) The new work said two changes improved performance: selecting optimal target sites within each gene of interest and engineering the P1 construct. The abstract said the P1 changes included adding a polyA10 sequence upstream of the intron’s internal guide sequence and an antisense sequence complementary to the target site and its upstream region. ### Why does the comparison with PIE matter? The abstract said the optimized STS strategy achieved “up to two-fold higher” self-circularization efficiency than the conventional permuted intron-exon, or PIE, method for long genes of interest of about 8 kilonucleotides. (pubmed.ncbi.nlm.nih.gov) The paper said the improved workflow worked across a wide range of gene lengths and outperformed PIE for long constructs. Rznomics had already positioned its approach against PIE in a 2023 company release describing its “self-circularized RNA structure” platform. (pubmed.ncbi.nlm.nih.gov) In that release, the company said some U.S. circRNA developers were using a group I intron ribozyme-based PIE method, while Rznomics’ own technology used a different circularization mechanism. ### What is circRNA, and why are companies trying to make it? (pubmed.ncbi.nlm.nih.gov) The *Nucleic Acids Research* abstract said circular RNAs are more stable than linear RNAs, which is one reason they are being studied for RNA vaccines and therapeutics. A 2015 *Nucleic Acids Research* review described circRNA as ring-shaped RNA and surveyed methods for generating it in vitro. Rznomics said in 2023 that circRNA’s closed structure gives it resistance to nucleases and could reduce reliance on modified nucleotides used in some linear RNA systems. (prnewswire.com) That characterization came from the company, not an independent head-to-head clinical comparison. ### Why is this a manufacturing story rather than a drug story? The September 2026 paper did not report human trial data, regulatory action or commercial supply agreements. (pubmed.ncbi.nlm.nih.gov) The study described a production workflow and compared circularization efficiency across methods and construct designs, according to the abstract. Rznomics framed the publication as a manufacturing advance that could support broader biomedical applications. (prnewswire.com) The abstract said the improved STS workflow enabled efficient circRNA production without extraneous sequences across a wide range of gene lengths. ### What should readers watch next? The next concrete checkpoint is whether Rznomics or outside groups publish follow-up data showing the optimized STS process in specific vaccine or therapeutic constructs. (pubmed.ncbi.nlm.nih.gov) The September 4 *Nucleic Acids Research* paper and its PubMed entry identify the named authors, method details and the comparison against PIE that future studies can test. (prnewswire.com)

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