The COVID-19 pandemic in 2020 brought mRNA technology to the forefront globally, with mRNA vaccines and drugs gaining widespread attention and unprecedented research interest. In the post-pandemic era, the number of mRNA R&D projects has surged exponentially. mRNA technology is reshaping the future landscape of vaccines, cancer immunotherapy, protein replacement therapies, gene editing, and even rare disease treatments, thanks to its unique mechanisms and significant potential.
As a pioneer with over a decade of experience in microbial expression system CRDMO services, Yao Hai Biotech has strategically established an mRNA technology platform and continuously enhanced its service capabilities. The company built an mRNA and CircRNA drug CRO service platform in 2022, and has since served more than 800 RNA CRO projects, with partners including universities, research institutes, and listed companies. This extensive scientific research service system acts as an "incubator" for technological innovation, laying a solid technical foundation for CDMO operations. Through vast R&D data and cutting-edge exploration, Yao Hai Biotech has validated and optimized core process parameters, accumulated substantial experience, and achieved seamless transition from laboratory-scale processes to industrial-scale production.
Yao Hai Biotech now possesses mature, end-to-end mRNA CRDMO service capabilities and has officially launched the "RNASUP" CDMO mRNA process development and industrialization platform. This platform comprises four core modules: plasmid template preparation, mRNA synthesis system optimization, linearization and scale-up production, and quality analysis and control. It integrates the entire industrial chain—from plasmid preparation, mRNA in vitro transcription and modification, and LNP delivery system development, to GMP drug substance production, formulation filling, and regulatory submission. The platform offers end-to-end solutions for mRNA vaccine/drug research institutions, from early process development to commercial production, fully addressing diverse needs across early R&D, clinical trials, and industrialization stages.
1. Plasmid Template Preparation Plasmid DNA (pDNA), serving as the template for mRNA in vitro transcription, directly influences mRNA synthesis efficiency and quality through its yield, purity, and supercoiled ratio. Leveraging over ten years of expertise in recombinant plasmids, Yao Hai Biotech has developed a mature platform for circular and linearized plasmid production. The platform utilizes large-scale fermentation and continuous lysis industrialization technologies, with fermentation capacities up to 2000L. The team has managed plasmid projects spanning from IND to Phase I, II, and III clinical trials, and NDA submissions, demonstrating extensive experience in scaled production. In 2024, the company successfully passed China's first registration on-site inspection and GMP compliance check for a recombinant plasmid drug, showcasing leading regulatory compliance.
During plasmid construction and fermentation, the platform employs high-copy, high-stability systems combined with high-density fermentation processes, achieving plasmid yields exceeding 1g/L within 30 hours, ensuring stable yield and quality from the source. In purification, multiple chromatography techniques precisely control residual host DNA/RNA, proteins, and endotoxins, achieving a supercoiled ratio ≥95% and a stable purification recovery rate of 30-45%. This ensures highly consistent supercoiled ratios and impurity levels for each DNA template batch, providing reliable support for efficient downstream mRNA synthesis.
2. mRNA Synthesis System Optimization mRNA synthesis is the technical core of the entire process. Yao Hai Biotech operates a mature mRNA synthesis platform with comprehensive industrial experience in process research, scaled production, and quality testing, supporting various types including conventional mRNA and self-amplifying mRNA (saRNA). Using industry-leading in vitro transcription (IVT) technology, the platform produces high-quality mRNA drug substances through systematic process development and condition optimization: integrity >90%, expected poly(A) distribution, endotoxin <0.1 EU/mL, and residual DNA <100 pg/mg.
The platform supports advanced capping methods (enzymatic capping, co-transcriptional capping) and nucleotide modification technologies (such as N1-methylpseudouridine modification), achieving capping efficiency over 95%, significantly enhancing mRNA translation efficiency and in vivo stability. Process optimization includes strict control of key byproducts like double-stranded RNA generated during IVT, effectively reducing inherent immunogenicity risks.
3. mRNA-LNP Encapsulation and Formulation The delivery system is a critical bottleneck for mRNA drug development. Yao Hai Biotech has established a mature lipid nanoparticle (LNP) encapsulation platform, offering CDMO services with high encapsulation efficiency and uniform particle size. Utilizing mainstream microfluidic technology and precise control of process parameters, the platform achieves LNP formulations with high encapsulation rates (typically >95%), uniform particle size (PDI<0.1), and excellent stability. The company also possesses capabilities for lipid component screening and formulation optimization, tailoring optimal delivery solutions for different mRNA molecules based on target and administration route, ensuring efficacy, safety, and stability.
4. GMP Production: Drug Substance and Formulation Advanced processes require robust production systems for implementation. Yao Hai Biotech's GMP facility spans over 20,000 square meters, housing 5 drug substance production lines (supporting plasmid production up to 2000L) and 2 sterile formulation lines (vials and pre-filled syringes), alongside a modern quality research center. The mRNA platform is equipped for scales ranging from R&D (tens of milligrams) to pilot (grams) and commercial production (tens of grams). The GMP production areas are designed and operated in strict compliance with NMPA, FDA, and EMA GMP standards, and the site has passed EU QP audits, meeting client needs across various stages and scales, ensuring smooth transition from R&D to commercialization.
5. RNAQua mRNA Quality Analysis and Control Quality is built-in and controlled. Yao Hai Biotech has established comprehensive quality research platforms for plasmids, mRNA, and LNPs, supported by an experienced QA/QC team. The platform's capabilities cover sequence integrity, capping efficiency, poly(A) tail length, as well as LNP encapsulation efficiency, particle size, zeta potential, and in vitro release, with full testing compliance for both Chinese and US regulatory submissions.
6. Service Advantages - Full-chain integration: End-to-end services covering plasmids, mRNA drug substance, and LNP encapsulation/formulation, ensuring seamless transitions and efficient project delivery. - Comprehensive lifecycle support: Services span process development, GMP clinical sample production, quality studies, and regulatory consultation, providing full support to accelerate R&D and registration. - Mature processes and extensive experience: Leveraging deep plasmid and mRNA project experience, the platform offers scalable processes with high capping efficiency and integrity, reducing impurity risks like double-stranded RNA, helping clients advance rapidly from PCC to IND and commercialization. - Global compliance and stable capacity: cGMP facilities meeting Chinese, US, and European standards, with successful official audits; flexible capacity from lab to commercial scale, delivering high quality and volume as needed. - Customized service models: Flexible support from small-scale process development to large-scale production, offering tailored R&D to commercialization assistance.
In the vast field of mRNA technology, Yao Hai Biotech not only supports drug R&D technical services but also partners in innovation. Moving forward, the company will continue optimizing and upgrading its integrated mRNA CDMO technology platform, guided by the core principles of technological platformization, service integration, and cost optimization. Committed to professional expertise, compliant quality, and reliable delivery, Yao Hai Biotech aims to empower global biopharmaceutical companies, promote the application of mRNA innovative therapies for more patients, and jointly build a new future for industry development.
As an active participant and witness to the rapid growth of the global biopharmaceutical industry, Yao Hai Biotech has long focused on microbial expression system CRDMO services, with business areas including recombinant proteins/peptides, nucleic acid drugs, nanobodies, recombinant plasmids, and novel recombinant vaccines. The company is dedicated to creating an open, integrated R&D and production service platform encompassing CRO, CDMO, and MAH. Through dedicated service and collaborative innovation, Yao Hai Biotech has consistently advanced over the past decade, continuously improving its R&D, production, and quality management systems. With robust platform technologies, comprehensive service capabilities, rich project experience, and leading scale advantages, it provides full-lifecycle CRDMO services from process development to commercial production for pharmaceutical companies worldwide, facilitating client drug development and contributing to global biopharmaceutical progress.