On August 23, 2024 Abogen Biosciences ("Abogen" or the "Company") reported a publication titled "Efficient circularization of protein-encoding RNAs via a novel cis-splicing system " in Nucleic Acids Research (Press release, Abogen Biosciences, AUG 23, 2024, View Source [SID1234646074]). In the article, Abogen has revealed a highly efficient RNA circularization cis-splicing system (referred to as the "Cis-System") which enables the production of circular RNA ("circRNA") with significantly extended protein expression, reduced innate immune activation, and flexible splice site design that offers substantial market potential.
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In recent years, circular RNA technology has gained significant attention from the biopharmaceutical industry, several circular RNA start-up companies raised a total of over 1 billion dollars in financing. Among the most notable are Flagship-incubated Sail Biomedicines (formed through the merger of Laronde and Senda Biosciences), which has raised nearly $800 million, and Orna Therapeutics, founded by MIT Professor Daniel Anderson, secured over $300 million in funding and recently acquired ReNAgade Therapeutics to accelerate its clinical development.
Abogen’s Cis-System-based circRNA not only has global IP, but also improves over PIE System
The conventional technology for circRNA synthesis is the PIE method (Permuted Introns and Exons), patented by Orna and other companies. However, the Cis-System not only circumvents the patent restrictions by the PIE system, but also simplifies the circularization process and makes it more suitable for industrial production. As described in the publication, the Cis-System embeds a ribozyme core structure at one end of the precursor RNA, rendering the need for additional spacer elements between the ribozyme and the target gene. This invention significantly enhances the circularization efficiency thus offers a "scarless" and highly efficient translation process with less process-related impurities.
The Cis-System-based circRNA shows promising prospects for the future
The Cis-System reported in this study can achieve high circularization efficiency with essentially unrestricted base and sequence composition at the ends of RNA molecules, enabling truly efficient and scarless circularization. Furthermore, the Cis-System is designed to be more flexible, allowing customization based on specific therapeutic needs and compatibility with RNA molecule of different lengths. All these technological advances will lead to more sustained protein expression, reduced innate immune stimulation, and potential tissue-specific expression, which potentially bring more hopes in chronic disease treatment and immunotherapies where repeated dosing may be required.
Dr. Shaojun Qi, Senior Scientist in mRNA Innovation department at Abogen commented:
"I deeply appreciated the innovative culture at Abogen which is crucial for our success in overcoming the key bottlenecks in circular RNA technology. "
Dr. Peng Gao, Vice President of Abogen (corresponding author of the publication), commented:
"After over two years of commitment and continuous efforts, our team has finally overcome the critical technical hurdle presented in circRNA technology. Preliminary results from further studies have reinforced the great value and application potential of this technology. We hope to rapidly translate this achievement into clinical solutions to address the unmet medical needs."
Link for the Original Paper
Shaojun Qi, Huiming Wang, Guopeng Liu, Qianshan Qin, Peng Gao, Bo Ying, Efficient Circularization of Protein-Encoding RNAs via a Novel Cis-Splicing System, *Nucleic Acids Research*, 2024;, gkae711, [View Source]" target="_blank" title="View Source]" rel="nofollow">View Source(View Source)