Our Custom mRNA Modification services help accelerate therapeutic discovery and obtain high-quality, high-efficacy mRNA constructs for biopharmaceutical research. We use advanced 5'-cap engineering and strategic nucleoside substitutions to ensure optimal pharmacokinetic and pharmacodynamic profiles of novel drug candidates.
Creative Biolabs' Custom mRNA Modification solves intrinsic IVT mRNA limitations—rapid degradation and innate immune activation. It provides highly stable, non-immunogenic mRNA constructs tailored for vaccines, personalized cancer therapy, and protein replacement.
Experience the Creative Biolabs Advantage - Get a Quote TodayCreative Biolabs' comprehensive modification platform focuses on the two most critical regions of the mRNA transcript to maximize its functional integrity and cellular acceptance.
Fig.1 The different modifications of mRNA, the chemical structure of the 5'-cap, and the common modification bases used to modify mRNA.1
The 5' cap is the regulatory and protective structure essential for both efficient translation initiation and protection from 5' exoribonucleases. We offer precision capping solutions:
The incorporation of modified nucleosides is the most critical step in creating a non-immunogenic and highly efficient mRNA. Our substitution services are driven by clinically relevant data:
| Modified Nucleotide | Function and Therapeutic Impact | Implementation |
|---|---|---|
| N1-methyl-pseudouridine (m1Ψ) | Unmatched Immune Evasion and Efficacy. The substitution of U with m1Ψ prevents recognition by innate immune sensors (TLR7/TLR8) and stabilizes the ribosome during elongation, leading to superior protein yield and prolonged half-life. | Standard in all high-efficacy mRNA constructs. |
| Pseudouridine (Ψ) | Highly effective base substitution that reduces immunogenicity compared to native U, suitable for applications where a strong, transient immune response may be beneficial. | Customizable for specific vaccine applications. |
| N6-Methyladenosine (m6A) and Derivatives | Modulates RNA secondary structure and RNA-protein interactions, influencing mRNA splicing, localization, and decay. Essential for fine-tuning the temporal expression profile of a therapeutic. | Strategic placement for regulatory control. |
| 5-Methylcytidine (m5C) / 2-Thiouridine (s2U) | Further chemical substitutions that contribute to overall immune tolerance and structural stability, particularly in UTRs and coding regions, are needed to optimize ribosome movement. | Utilized for highly complex structural mRNA engineering. |
To initiate a project, clients typically provide the following concrete inputs:
Creative Biolabs scientists analyze clients' templates, target proteins, and therapeutic goals, then select optimal 5' cap analogs (ARCA vs. enzymatic Cap 1), required modified nucleosides (m1Ψ commonly used), and UTR sequences.
The DNA template is transcribed with proprietary high-yield polymerases, along with selected modified nucleoside triphosphates and 5' cap analog.
Crude mRNA undergoes rigorous purification to remove unreacted nucleotides, truncated RNA, and immunogenic dsRNA byproducts.
Final modified mRNA is tested in vitro: nuclease protection assays for stability, and reporter gene expression in target cell lines for translational yield.
Stable, high-efficacy mRNA is prepared per client needs—often lyophilized or in ready-to-use solution—for downstream LNP encapsulation.
Upon project completion, clients receive specific, tangible outputs:
The typical timeframe for this custom mRNA modification service ranges from 6 to 10 weeks, depending on the complexity of the sequence, the novelty of the required nucleoside substitutions, and the scale of the synthesis requested.
Creative Biolabs offers an end-to-end mRNA engineering partnership, leveraging our expertise to optimize every aspect of your therapeutic construct for peak performance and safety. Our services are built around flexibility, scalability, and uncompromising quality, ensuring your project moves seamlessly from research to the clinical stage.
Customized Sequence and Element Optimization
We avoid fixed protocols; experts analyze your specific gene and target cell type to optimize UTR elements, coding sequence codon usage, and poly(A) tail length for maximum in vivo translational efficiency and stability.
One-Stop Scale-Up Production
Creative Biolabs offers seamless one-stop service from milligram-scale research batches to multi-gram GMP-grade clinical material. Scalable systems eliminate costly, complex tech transfer between phases.
Precision Capping and Nucleoside Strategy
We ensure the most native-like cap structure. Also, we strategically incorporate non-canonical nucleosides (m1Ψ, Ψ, m5C, m6A derivatives) customized to balance stability, translation, and immune stealth needs.
Efficient Upstream/Downstream Process Development
Our integrated approach includes rapid, high-yield linearized DNA template preparation (upstream) and proprietary high-resolution HPLC-based mRNA purification (downstream) for high integrity and purity in sensitive applications.
Clinical-Grade QC and QbD Compliance
We follow Quality-by-Design (QbD) principles, using high-standard QC tools (HPLC, LC/MS for capping efficiency, dsRNA quantification) to ensure each batch is clinical-trial-ready with a full audited documentation package.
Unmatched dsRNA Removal
Creative Biolabs focuses on minimizing immunogenic dsRNA impurities. Stringent purification protocols and validated quality systems guarantee ultra-low dsRNA content, critical for reducing toxicity and enabling successful clinical outcomes.
A: Unmodified mRNA is rapidly degraded and often triggers a massive inflammatory response, severely limiting its therapeutic viability. Creative Biolabs' m1Ψ-modified mRNA is fundamentally different; it's a stealth molecule. It bypasses TLR sensors, resists cellular degradation pathways, and translates proteins at significantly higher levels. This transformation is critical for in vivo applications, allowing you to achieve therapeutic effects with lower dosing and improved safety.
A: Absolutely. While m1Ψ handles the bulk of immune evasion and stability, the 5' cap, particularly an ARCA or Cap 1 structure, is required to initiate protein synthesis efficiently and protect against 5' exonucleases. The two modifications work synergistically: m1Ψ prevents the immune system from shutting down translation, and the cap ensures the translation process starts strong and lasts longer.
A: Think of mRNA modification as optimizing the engine, and LNP engineering as optimizing the vehicle. mRNA modification (the engine) ensures the transcript is stable and highly active once inside the cell. LNP engineering (the vehicle) ensures the mRNA safely crosses the cell membrane. Both are typically required for successful in vivo therapeutic delivery and efficacy, and Creative Biolabs provides integrated services for both.
Creative Biolabs provides an unparalleled one-stop Custom mRNA Modification platform, specializing in synthesizing, purifying, and modifying high-purity mRNA constructs. Partner with us to efficiently advance your research from bench to clinic.
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