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Custom mRNA Chemical Synthesis Service

Introduction mRNA Chemical Synthesis Workflow What We Can Offer FAQ

Introduction

Custom mRNA chemical synthesis is an advanced non-enzymatic method with better control and precision than traditional enzymatic approaches. It enables atomic-level sequence control and site-specific chemical modifications, addressing immunogenicity/stability issues to speed research-to-clinical development—critical for high-purity, effective mRNA for vaccines and non-coding immunotherapies.

Creative Biolabs' corresponding service solves challenges like high-fidelity transcripts and IVT limitations via an advanced solid-phase platform, producing pure, consistent, stable mRNA with atomic-level fidelity and site-specific modifications for diverse uses.

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Custom mRNA Chemical Synthesis

Linear mRNA Synthesis

This is the most common form of synthesis, where the mRNA molecule is built as a single, linear strand from 5' to 3' on a solid support. This method is highly flexible and allows for the synthesis of transcripts of varying lengths with precise sequence control and the ability to incorporate modifications at any position.

RNA solid-phase synthesis cycle. (OA Literature)Fig.1 Schematic diagram of the solid-phase synthesis method of RNA.1,3

Circular mRNA Synthesis

While less common than linear, circular mRNA (circRNA) is a growing field of interest due to its enhanced stability and long-lasting protein expression. CircRNA lacks free ends, making it resistant to degradation by exonucleases. Our service is capable of producing circRNA via advanced ligation techniques, offering a robust platform for long-term expression applications.

Overview of existing circularization approaches. (OA Literature)Fig.2 The existing methods for synthesizing circular RNA.2,3

Synthesis Methods

Our primary method is solid-phase chemical synthesis using phosphoramidite chemistry. This allows for a stepwise, controlled addition of each nucleotide to the growing chain. This approach provides several key advantages: high purity of the final product, the ability to incorporate a diverse range of chemical modifications, and precise control over the overall sequence length and integrity.

Workflow

Required Starting Materials

  • To start the project, clients usually provide the mRNA sequence, linear DNA template (if available), and detailed specs for desired chemical modifications (e.g., N1-methylpseudouridine (m1ψ), 5-methylcytidine (m5C))
Consultation & Design
Sequence Optimization

Project Consultation & Design

  • Our experts collaborate with you to review project goals, refine mRNA sequences for optimal expression/stability, and assist with codon optimization, UTR design, and modified base selection.

Solid-Phase Synthesis

  • mRNA is built nucleotide-by-nucleotide on a solid support via advanced phosphoramidite chemistry, ensuring high fidelity and precise site-specific incorporation of modified bases.
Chemical Modifications
Synthesis & Purification

Cleavage & Deprotection

  • Synthesized mRNA is cleaved from the solid support and deprotected (removing nucleobase protecting groups) to get the fully functional final mRNA.

Advanced Purification

  • Multi-stage purification (including HPLC) removes residual reagents, truncated sequences, and impurities, ensuring high, verifiable product purity.
Quality Control & Validation
Delivery & Support

Comprehensive Quality Control (QC)

  • Every batch undergoes strict QC: mass spectrometry (verify molecular weight), gel electrophoresis (check full-length transcripts), and functional assays (assess biological activity) to confirm identity, purity, integrity, and concentration.

Final Deliverables

Upon completion, you receive purified mRNA plus a detailed Certificate of Analysis (CoA) with full QC report, synthesis summary, and data for regulatory filings.

Consultation & Design
Sequence Optimization

Estimated Timeframe

Typical 4-8 weeks, depending on mRNA length, modification complexity, and specific QC needs. We provide a precise timeline after a thorough review.

What We Can Offer

One-stop solution
One-stop solution for Custom mRNA Chemical Synthesis, guiding you from initial design to large-scale, GMP-grade production.

Advanced phosphoramidite chemistry
Advanced phosphoramidite chemistry for superior sequence fidelity and the precise, site-specific incorporation of a wide range of modified nucleotides.

Exceptional scalability
Exceptional scalability to meet your needs, from small-scale discovery research to multi-gram quantities for preclinical and clinical development.

Full documentation and transparency
Full documentation and transparency to support regulatory submissions, adhering to Good Manufacturing Practice (GMP) principles.

Superior Purity
Our multi-stage purification process, including HPLC, effectively removes impurities and byproducts such as double-stranded RNA (dsRNA), which can trigger unwanted innate immune responses. Published data confirms our ability to deliver ultra-pure mRNA.

Reliable and Reproducible
Our standardized, validated processes ensure lot-to-lot consistency and scalability, offering a reliable pathway from early-stage research to GMP-grade manufacturing.

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Customer Reviews

  • [Improved Vaccine Efficacy] "Using Creative Biolabs' Custom mRNA Chemical Synthesis in our research has significantly improved the consistency and efficacy of our in vivo immunization studies. The low dsRNA content meant we observed a robust, focused immune response with minimal off-target effects, which was a major concern with previous suppliers."

    - Aisha Ada, Ph.D., R&D Director

  • [Accelerated Drug Screening] "The high purity and consistent quality of the mRNA from Creative Biolabs have significantly facilitated our high-throughput screening for novel protein-based drug candidates. We can trust that any functional differences we see are due to our constructs, not the mRNA itself."

    - James Ues, Scientist, Bioanalytical Services

  • [Enhanced Translational Efficiency] "We found that the precise 5' capping and poly(A) tailing services from Creative Biolabs dramatically enhanced the translational efficiency of our mRNA in difficult-to-transfect cell lines, which directly improved our downstream protein expression levels for structural biology studies."

    - Carlos Las, Principal Investigator, Structural Biology

FAQs

Q: Why should I choose chemical synthesis over in vitro transcription (IVT)?

A: While IVT is a useful tool for initial research, it is an enzymatic process prone to impurities and sequence errors. Chemical synthesis, in contrast, offers a defined, atomic-level control over the sequence and allows for the precise incorporation of modifications, which is crucial for reducing immunogenicity and enhancing stability for therapeutic applications.

Q: Can you help with the design of my mRNA sequence to improve its performance?

A: Absolutely. We offer expert consultation services to assist with sequence optimization, including codon optimization for enhanced protein expression and the design of UTRs that can improve mRNA stability and translational efficiency. Our team is here to help you get the best results from your project.

Q: How do you ensure the purity and quality of the final mRNA product?

A: We employ a multi-step purification process, including advanced HPLC, to ensure high purity. Every batch is subjected to rigorous quality control testing, including mass spectrometry and gel electrophoresis, and we provide a detailed Certificate of Analysis so you can have complete confidence in your materials.

Q: What types of chemical modifications can you incorporate into the mRNA?

A: We can incorporate a wide variety of modified nucleosides to meet your specific needs. Common examples include N1-methylpseudouridine (m1ψ), pseudouridine (ψ), and 5-methylcytidine (m5C), all of which are critical for enhancing stability and reducing the innate immune response.

Q: What is the benefit of working with Creative Biolabs for large-scale production?

A: Our chemical synthesis platform is highly scalable, and we have established manufacturing processes that can bridge the gap from research-grade quantities to GMP-grade material required for clinical trials. Our consistent and well-documented workflow simplifies your regulatory process and ensures reliability at every stage.

To learn more about our offerings and to discuss how our Custom mRNA Chemical Synthesis service can be tailored to your specific project needs, please do not hesitate to reach out. Our team of experts is ready to provide you with detailed information, a customized proposal, and technical guidance to accelerate your research and development efforts.

Contact Our Team for More Information and to Discuss Your Project

Hot IVT Vectors

Cat. No Product Name Promoter
CAT#: GTVCR-WQ001MR IVTScrip™ pT7-mRNA-EGFP Vector T7
CAT#: GTVCR-WQ002MR IVTScrip™ pT7-VEE-mRNA-EGFP Vector T7
CAT#: GTVCR-WQ003MR IVTScrip™ pT7-VEE-mRNA-FLuc Vector T7
CAT#: GTVCR-WQ87MR IVTScrip™ pT7-VEE-mRNA-Anti-SELP, 42-89-glycoprotein Vector T7

Hot IVTScrip™ mRNA Transcript

Cat. No Product Name Type
CAT#: GTTS-WQ001MR) IVTScrip™ mRNA-EGFP (Cap 1, 30 nt-poly(A)) Reporter Gene
CAT#: GTTS-WK18036MR IVTScrip™ mRNA-Human AIMP2, (Cap 1, Pseudo-UTP, 120 nt-poly(A)) Enzyme mRNA
(CAT#: GTTS-WQ004MR) IVTScrip™ mRNA-Fluc (Cap 1, 30 nt-poly(A)) Reporter Gene
(CAT#: GTTS-WQ009MR) IVTScrip™ mRNA-β gal (Cap 1, 30 nt-poly(A)) Reporter Gene

References

  1. Flemmich, Laurin, Raphael Bereiter, and Ronald Micura. "Chemical synthesis of modified RNA." Angewandte Chemie International Edition 63.22 (2024): e202403063. https://doi.org/10.1002/anie.202403063.
  2. Wasinska-Kalwa, Malgorzata, et al. "Chemical circularization of in vitro transcribed RNA for exploring circular mRNA design." Nature Communications 16.1 (2025): 6455. https://doi.org/10.1038/s41467-025-61775-1.
  3. Distributed under Open Access license CC BY 4.0, without modification.
All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.