Nucleotides Modification Services provides chemical expertise to customize the synthetic mRNA's backbone and bases. Key modifications reduce immunogenicity, boost stability and translation efficiency—their accurate site-specific incorporation defines next-gen mRNA therapeutics, supported by literature for in vivo success.
Our Custom Nucleotides Modification Services use advanced solid-phase synthesis and enzymatic ligation for site-specific modifications, turning raw RNA into high-performance therapeutic materials. We enhance stability, cut unwanted immune activation, and boost translation efficiency—key for preclinical candidates, and foundational for single-cell multi-omics validation and clinical translation.
Discover How We Can Help - Request a ConsultationOur custom services provide access to advanced modified nucleosides necessary for high-performance therapeutic mRNA.
Fig.1 Modified mRNA-based therapy by chemically modified nucleotides.1
Pseudouridine (Ψ) is an isomer of uridine found abundantly in natural RNA. When incorporated into synthetic mRNA, typically as N1-methylpseudouridine (N1Ψ), it functions to dampen the innate immune response mediated by Toll-like receptors. This modification is foundational for virtually all successful clinical mRNA vaccines and therapeutics, providing the immune stealth necessary for effective cellular translation.
2-Thiouridine (s2U) modification increases the hydrophobicity of the RNA molecule, enhancing the binding of specific tRNA molecules. This modification can be leveraged to subtly alter the protein translation rate and potentially affect the stability of the mRNA molecule. Its utility is explored in structural biology studies and in fine-tuning translational kinetics for therapeutic protein expression.
5-Methylcytidine (m5C) is another common nucleoside modification that occurs naturally in mRNA. Incorporating m5C into synthetic transcripts further contributes to enhanced stability and reduced immunogenicity, often working synergistically with Pseudouridine. This modification also plays a role in regulating mRNA export and translation in the cell, making it a powerful tool in chemical optimization.
N6-Methyladenosine (m6A) is the most abundant internal modification in mammalian mRNA. As an epitranscriptomic marker, it regulates mRNA splicing, stability, translation, and decay. While challenging to incorporate site-specifically, m6A modification services are essential for researchers studying or leveraging this regulatory switch for applications such as stem cell differentiation or gene expression control.
Our workflow is designed for clarity and scientific rigor, ensuring potential clients understand the intricate steps involved in creating custom, high-purity, modified mRNA.
| Stage | Activity |
|---|---|
| Project Consultation & Design | Detailed discussion of the target gene, desired protein expression level, and required modifications (e.g., Ψ, m5C). |
| Raw Materials & Sequence Acquisition | Client provides the target sequence or cDNA template, and specifies 5' capping (e.g., Cap 1) and poly-A tail length. |
| Solid-Phase Synthesis & Incorporation | Iterative chemical synthesis using advanced solid-phase techniques to incorporate modified nucleosides site-specifically. New protection concepts are used to overcome size limitations. |
| Capping & Ligation | All-chemical synthesis of the 5'-cap structure is performed. Enzymatic ligation is used to join shorter, high-purity modified segments, yielding the final, full-length mRNA. |
| Purification & Quality Control (QC) | Rigorous HPLC purification, followed by analytical testing including mass spectrometry (MS) for sequence and modification confirmation, and integrity analysis (gel electrophoresis). |
Required Starting Materials: Clients typically provide 2-3 of the following: Target cDNA or gene sequence, Desired 5' cap and poly-A tail length specifications, and Target cells or application (e.g., T-cell activation in immunotherapy).
Final Deliverables: Clients receive: High-Purity Modified mRNA (lyophilized or in solution), a Comprehensive QC Report (including MS and Purity data), and a Detailed Synthesis Protocol.
Estimated Timeframe: The typical timeframe for this service ranges from 6 to 12 weeks, depending on the complexity of the required modifications (e.g., Ψ vs. 2'-N modifications) and the final length of the transcript.
At Creative Biolabs, we are uniquely positioned to handle the complexity and precision required for manufacturing next-generation mRNA. Our offerings focus on custom chemical solutions that guarantee enhanced performance and reduced immunogenicity for your therapeutic candidates.
Custom Site-Specific Modification
Offer site-specific incorporation of non-canonical nucleosides (Pseudouridine Ψ, 5-Methylcytidine m5C, specialized ribose modifications) to go beyond bulk IVT limitations.
High-Fidelity Chemical Synthesis
Use advanced solid-phase synthesis with novel protection chemistries to overcome size limits, ensuring high purity and yield of long RNA transcripts.
Complex Transcript Engineering
Provide expertise in all-chemical 5'-cap synthesis and enzymatic ligation to produce full-length, multi-domain mRNA with multiple distinct modifications—essential for personalized cancer vaccines.
Unrivaled Purity and Quality Control
Apply MS and rigorous HPLC purification to verify each modification's precise location and integrity, guaranteeing ultra-high purity for sensitive in vivo studies.
Reduced Immunogenicity Guarantee
Chemically optimize transcripts via validated modifications to significantly reduce innate immune signaling, ensuring high translational efficiency and stability in target cells.
Integrated Multi-Omics Ready
Design synthesis protocols to support downstream high-resolution analysis, providing high-quality starting material for Single-Cell Multi-Omics (S-C M-O) validation.
A: We ensure the integrity of complex transcripts by utilizing enzymatic ligation to join highly purified, chemically synthesized segments, ensuring the full-length molecule is free of truncated byproducts. Our Comprehensive QC Report confirms the integrity, sequence, and modification sites via mass spectrometry and gel analysis.
A: Standard IVT kits generally limit you to a few common modifications, often with high batch-to-batch variability. Creative Biolabs provides site-specific, custom incorporation of a wide range of challenging modifications (e.g., 2'-OCF3, m6A), resulting in superior purity and consistency—essential factors that de-risk preclinical toxicity and enhance therapeutic efficacy.
A: While chemical synthesis has a higher initial cost than bulk IVT, the superior purity, defined modification sites, and significantly reduced immunogenicity ultimately translate to lower failure rates and accelerated time-to-clinic. For complex, personalized medicines, this precision is a non-negotiable factor that yields a better return on investment.
A: Custom-modified RNA is crucial for single-cell functional analysis (scMulti-Omics) where precise, non-immunogenic delivery is paramount. It is also used extensively in structural biology (e.g., using deazapurine bases) and in research focused on epitranscriptomics (m6A) to study gene regulation and stem cell differentiation.
Creative Biolabs Nucleotides Modification Services provides chemically precise, high-purity custom mRNA transcripts to solve key therapeutic RNA challenges: immunogenicity and instability. Using advanced solid-phase synthesis and enzymatic ligation, it delivers critical therapeutic material for cancer immunotherapy, gene therapy, and advanced biological research.
Contact Our Team for More Information and to Discuss Your Project| 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 |
| 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 |
Reference
