Nucleoside-Modified mRNA Synthesis for Therapeutic Development
Overview
Unlock the therapeutic potential of mRNA with precisely engineered nucleoside modifications.
Nucleoside modifications are a proven strategy to mitigate the intrinsic immunostimulatory activity of exogenous mRNA while enhancing its stability and translational efficiency. By incorporating modified nucleosides such as pseudouridine, N1-methylpseudouridine, or 5-methylcytidine, synthetic mRNA can evade innate immune sensors and achieve prolonged protein expression in target cells.
Our end-to-end service covers every step from sequence design and template preparation through IVT, capping, purification, and poly(A) tail optimization. We provide research-grade and preclinical-grade mRNA, tailored to your specific therapeutic application. Each batch is rigorously characterized to ensure low endotoxin, high capping efficiency, and defined poly(A) tail length.
This service is designed for biotech and pharma teams developing mRNA-based therapies for rare genetic diseases, enzyme replacement, and other protein-replacement or vaccine applications. We support functional validation in relevant cell models, including iPSC-derived cells, to de-risk your candidate before in vivo studies.
Key Features of Our Nucleoside-Modified mRNA Synthesis Service
Complete Design Flexibility
We optimize sequence features including codon usage, untranslated regions (UTRs), and poly(A) tail length to maximize translation and stability. Custom modifications can be introduced at specific positions or throughout the transcript.
Wide Range of Modified Nucleosides
Choose from pseudouridine, N1-methylpseudouridine, 5-methylcytidine, 2′-O-methyl modifications, and others. We also support point-modified mRNA for precise incorporation of single modified nucleosides.
Advanced Purification and QC
HPLC purification removes dsRNA and other impurities to reduce innate immune activation. Each batch is analyzed for capping efficiency, poly(A) tail length homogeneity, endotoxin, and sterility.
Scalable from Research to Preclinical
Our platform supports milligram to gram-scale synthesis under controlled conditions, enabling seamless transition from screening to lead optimization and preclinical studies.
Integrated Functional Validation
We provide optional support for in vitro assessment in relevant cell models, including protein expression analysis, immunogenicity profiling, and phenotypic assays.
Available Nucleoside Modifications
Select from a panel of chemically modified nucleosides to tailor the properties of your mRNA for optimal therapeutic performance.
- Pseudouridine (Ψ): Naturally occurring modification that enhances translation and reduces activation of Toll-like receptors and RIG-I. Commonly used in therapeutic mRNA.
- N1-Methylpseudouridine (m1Ψ): A synthetic derivative that further suppresses innate immune sensing and increases translational capacity compared to pseudouridine.
- 5-Methylcytidine (m5C): Incorporated to improve mRNA stability and translation efficiency while reducing immunogenicity.
- 2′-O-Methyl Modifications: Partial or full substitution of 2′-OH groups to enhance nuclease resistance and reduce innate immune recognition.
- Point-Modified mRNA: Site-specific incorporation of a single modified nucleoside at a defined position, enabling mechanistic studies and fine-tuning of mRNA properties.
Our Integrated Workflow
From design to delivery, our streamlined process ensures high-quality, functional nucleoside-modified mRNA for your research.
- Design & Template Preparation: We optimize sequence elements including UTRs, codon usage, and poly(A) tail length. A linearized plasmid or PCR template is generated and verified by sequencing.
- In Vitro Transcription & Capping: IVT is performed using T7 RNA polymerase with modified NTPs and a capping analog (e.g., CleanCap). Co-transcriptional capping achieves high efficiency while preserving integrity.
- Purification & Poly(A) Tailing: Following DNase treatment, the mRNA is purified by HPLC to remove dsRNA and residual enzymes. An optional poly(A) tail can be added enzymatically for precise length control.
- Quality Control & Delivery: Each batch is analyzed for identity, purity, capping efficiency, poly(A) tail distribution, endotoxin, and sterility. A comprehensive QC report accompanies the final product.
End-to-End Support
Our team collaborates with you from sequence design through final QC, providing documentation and data packages to support regulatory submissions and IND-enabling studies.
Project Timeline
Our process is designed to align with your project milestones, from early research to preclinical development.
- Design Review: Sequence optimization and modification strategy are finalized with your input.
- Template Synthesis & QC: Plasmid or PCR template is produced and verified by sequencing.
- IVT & Capping: In vitro transcription with modified NTPs and co-transcriptional capping.
- Purification & Poly(A) Tailing: HPLC purification and optional enzymatic poly(A) tail addition.
- Final QC & Release: Comprehensive analysis and shipping of the final mRNA product with QC documentation.
Timelines are confirmed upon project scoping and are dependent on sequence complexity, modification requirements, and scale.
Rigorous Quality Control
Quality is embedded in every step of our mRNA synthesis service. We employ HPLC purification to remove double-stranded RNA and other process-related impurities that can trigger innate immune responses. This step is critical for achieving the low immunogenicity profile required for therapeutic applications.
Each batch is characterized by a suite of analytical methods: UV/Vis spectrophotometry for concentration, agarose gel electrophoresis or capillary electrophoresis for integrity, capping efficiency via LC-MS or enzymatic assay, poly(A) tail length distribution using enzymatic methods, and endotoxin and sterility testing. Results are summarized in a detailed certificate of analysis.
Our facility operates under controlled conditions to ensure lot-to-lot consistency. We also provide optional additional testing such as bioactivity assessment in cell-based assays to confirm protein expression and functional activity.
Why Choose Our Nucleoside-Modified mRNA Synthesis Service?
- Integrated End-to-End Service: We handle everything from sequence design to functional validation, reducing the need for multiple vendors and simplifying project management.
- Customizable Modification Profiles: Choose from a broad panel of modified nucleosides and point-modification strategies to tailor mRNA properties to your specific therapeutic need.
- Rigorous Quality Control: HPLC purification and comprehensive analytical characterization ensure low immunogenicity, high purity, and defined product attributes.
- Scalable Production: Our platform supports scales from milligrams to grams, enabling seamless progression from early research to preclinical studies.
- Regulatory Experience: We provide documentation and data packages that support IND-enabling studies and regulatory submissions, backed by our team's expertise in therapeutic mRNA development.
Cell Models for Functional Validation
Assess the performance of your nucleoside-modified mRNA in biologically relevant cell systems to de-risk your candidate before in vivo studies.
- iPSC-Derived Cells: Disease-relevant human models such as cardiomyocytes or neurons for evaluating therapeutic enzyme expression and phenotypic correction.
- Primary Cells: Primary hepatocytes, fibroblasts, or immune cells for testing mRNA uptake, translation, and immunogenicity in a native cellular context.
- Established Cell Lines: HEK293, HeLa, or other standard lines for initial screening of protein expression and dose-response.
- 3D Organoids and Co-Cultures: Complex tissue models for assessing functional impact and off-target effects in a more physiologically relevant environment.
- Immune Cells: Peripheral blood mononuclear cells (PBMCs) or dendritic cells for evaluating innate immune activation and antigen presentation.
Contact Us
Whether you are optimizing mRNA stability and immunogenicity, developing novel nucleoside chemistries, or scaling up production of modified mRNA, our synthesis team can support your program from design through analytical characterization. Contact us today to discuss your project requirements.