One-step mRNA synthesis utilizing Cap analogs represents a fundamental and widely adopted methodology in mRNA pharmaceutical production. Ongoing optimization of this process, coupled with advancements in small-scale, high-throughput synthesis platforms, serves as a critical foundation for the continued progression of mRNA therapeutics.
ENO Bio has established a robust, standard one-step mRNA synthesis platform based on commercially available Cap1 analogs. This platform enables clients to achieve high-quality mRNA synthesis, meeting the essential requirements for a diverse range of mRNA drug development initiatives.
Building upon this core capability, ENO Bio has further innovated by developing a proprietary, next-generation one-step synthesis technology employing novel, in-house designed Cap2 analogs. This advanced system not only guarantees high-quality mRNA production but also confers tissue-specific expression properties. It provides clients with a differentiated strategy to address more complex clinical application needs, while simultaneously achieving significant intellectual property breakthroughs in mRNA synthesis technology.
NO Bio has established foundational capabilities based on third-generation one-step mRNA synthesis technology, providing clients with high-quality mRNA synthesis to meet diverse custom synthesis and product development needs. This platform has supported multiple clients in obtaining clinical trial approvals and advancing into clinical studies for various mRNA products, including COVID-19 mRNA vaccines and mRNA-based oncology therapeutics.
However, the third-generation one-step mRNA synthesis method is constrained by stringent patent protections held by TriLink. The Cap analog-based co-transcriptional mRNA synthesis technology has become a critical "bottleneck" in the global mRNA competitive landscape and a key focal point of industry attention.
In response, ENO Bio has developed a fourth-generation one-step co-transcriptional mRNA synthesis technology utilizing its proprietary Cap2 analog, RHCap. This innovation achieves a comprehensive breakthrough in both Cap analog structure and mRNA synthesis methodology, overcoming existing intellectual property barriers and technological monopolies in the field. The technology demonstrates consistent quality performance across multiple batches of different mRNA sequences, with capping rates consistently exceeding 95%. In pilot-scale production, mRNA yields exceed 600 mg per 100 mL reaction system.
More importantly, mRNA synthesized using the RHCap-based one-step method can be endowed with tissue specificity by selecting different Cap2 analog structures. This enables enhanced cellular immune responses or higher target tissue protein expression levels, while reducing off-target delivery effects and improving safety profiles. This technology provides a foundational support for the broader clinical application of mRNA-based therapies.