Custom Nucleic Acid Production
Custom Oligonucleotide Synthesis & Modification Services
Combining advanced synthesis technology with extensive modification capabilities to deliver precisely engineered oligonucleotides that meet your highest quality standards. Our comprehensive technical expertise and analytical excellence ensure superior product performance for your innovative research.
Oligonucleotide synthesis has emerged as a pivotal technology underpinning therapeutic oligonucleotides, antisense drugs, siRNA therapeutics, and advanced molecular diagnostic platforms. The complexity of these applications presents substantial technical challenges, from achieving ultra-high purity levels (>95%) and incorporating site-specific modifications to ensuring scalable manufacturing processes with exceptional batch consistency. Critical parameters such as coupling efficiency, deprotection conditions, and chromatographic resolution must be precisely controlled to meet stringent regulatory requirements and application-specific demands. The increasing complexity of oligonucleotide-based therapeutics, particularly those incorporating multiple modifications or requiring gram-scale synthesis, necessitates sophisticated technical capabilities and robust quality control systems.
To address these challenges, we provide comprehensive custom nucleic acid production services powered by advanced phosphoramidite chemistry and automated solid-phase synthesis platforms. Our capabilities encompass the entire spectrum of oligonucleotide synthesis requirements - from unmodified sequences to complex modified constructs, backbone modifications, and conjugated oligonucleotides, all available at scales ranging from milligrams to grams. Each synthesis undergoes rigorous quality control including HPLC analysis, mass spectrometry characterization, and sequence verification, ensuring product integrity and batch-to-batch consistency. Our optimization-driven approach, combined with state-of-the-art purification techniques and analytical methods, enables us to consistently deliver high-quality oligonucleotides that meet the most demanding specifications for both research applications and therapeutic development.
WHAT WE DO?
As a leading provider of custom nucleic acid synthesis services, we specialize in delivering high-quality oligonucleotides engineered to meet the exacting requirements of modern biomedical research and therapeutic development. Our advanced synthesis platforms, coupled with custom oligonucleotide modification strategies and rigorous quality control systems, enable us to produce oligonucleotides with exceptional purity, accuracy, and batch-to-batch consistency. Our synthesis capabilities extend from conventional RNA/DNA sequences to sophisticated modified constructs, including therapeutic-grade oligonucleotides, regulatory RNAs, and structurally complex nucleic acids. Below is a detailed overview of our synthesis portfolio, highlighting the unique characteristics and applications of each oligonucleotide type. Additionally, we provide large-scale oligonucleotide production services at gram to kilogram scale, maintaining superior quality and consistency to support your transition from research to commercial manufacturing.
Table 1 Custom Oligonucleotide Portfolio: Comprehensive Synthesis Capabilities and Applications
Natural oligonucleotides are inherently vulnerable to nuclease degradation and face challenges in cellular internalization and tissue distribution. Strategic chemical modifications have emerged as critical tools to overcome these limitations, enabling the optimization of ADME profiles and target interaction characteristics. Our comprehensive modification portfolio encompasses a wide range of nucleobase, sugar, and backbone modifications, along with specialized conjugation options - from 2'-modifications and LNA/BNA incorporation to phosphorothioate linkages and targeting ligands. Below is a detailed overview of our available chemical modifications, each engineered to address specific performance parameters in oligonucleotide development. View more about our Oligonucleotide Modification Services .
Table 2 Available Chemical Modifications: Properties, Benefits, and Applications
| Base Modifications | Sugar Modifications | Backbone Modifications | Terminal Modifications | Conjugations |
|---|---|---|---|---|
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HOW WE DO?
Creative Biolabs' oligonucleotide synthesis platforms vary in speed and flexibility, normally we use solid-phase synthesis to produce an oligonucleotide. This means that oligonucleotides will be tethered to a solid surface when they are being made. In other words, within the solid-phase synthesis, an oligonucleotide being assembled is covalently bound, via its 3'-terminal hydroxyl group, to solid support material and remains attached to it over the entire course of the chain assembly. This synthesis process begins with the 3'-most nucleotide and proceeds through a series of cycles composed of four steps that are repeated until the 5'-most nucleotide is attached. These four steps are deprotection (A), condensation (B), capping (C), and oxidation (D) shown in Figure 1.
Figure 1. The phosphoramidite approach for oligonucleotide synthesis.1
Our custom oligonucleotide synthesis service offers a flexible and comprehensive workflow designed to accommodate diverse project requirements. Whether you need complete end-to-end support from initial sequence design to final delivery, or specific services at any particular stage, our workflow can be tailored to seamlessly integrate with your existing processes. Each step is customizable to meet your specific technical requirements, quality standards, and timeline objectives. From initial consultation and sequence optimization to scale-up production and analytical characterization, you can engage our services at any point in the development process. Below is our standard workflow, which can be modified based on your specific project needs:
Initial Consultation & Sequence Submission
- Technical consultation with our experts
- Sequence submission and specifications review
- Feasibility assessment
- Scale and modification requirements evaluation
- Preliminary timeline estimation
Design & Optimization
- Sequence analysis and optimization recommendations
- Modification strategy development
- Synthesis route planning
- Quality control parameters definition
- Production scale optimization
Synthesis & Production
- Automated solid-phase synthesis
- Real-time quality monitoring
- Modification incorporation
- Controlled deprotection process
- Initial analytical testing
Purification & Analysis
- Multi-step purification process
- HPLC/UPLC analysis
- Mass spectrometry verification
- Purity assessment
- Structure confirmation
Quality Control & Documentation
- Full analytical characterization
- Batch record review
- Certificate of Analysis generation
- Stability assessment
- Quality documentation preparation
Final Release & Delivery
- Quality review and final release
- Custom packaging according to specifications
- Temperature-controlled shipping
- Tracking information provision
- Documentation package delivery
SYNTHESIS PLATFORMS
Our state-of-the-art oligonucleotide synthesis platform integrates advanced DNA/RNA synthesizers with high-throughput parallel synthesis technology, enabling us to deliver custom oligonucleotides with exceptional purity and accuracy. The platform features industry-leading Applied Biosystems and Mermade synthesizers, coupled with sophisticated HPLC and mass spectrometry systems for rigorous quality control. This comprehensive setup allows us to efficiently synthesize oligonucleotides of 2-200 bases in length and other challenging oligos, while accommodating various modifications including fluorescent labels, biotin, amino modifiers, modified bases, etc.
Our facility is equipped with cutting-edge purification and analysis instruments, including advanced UPLC systems and high-resolution mass spectrometers, ensuring that every oligonucleotide meets the most stringent quality standards. This integrated platform enables us to maintain consistent batch-to-batch reproducibility while offering rapid turnaround times and scalable synthesis capabilities from micromole to millimole scales.
WHY CHOOSE US?
Technical Excellence
Our cutting-edge synthesis platforms integrate advanced automation systems with sophisticated process controls, enabling us to handle the most challenging oligonucleotide syntheses. From standard sequences to complex modifications, our technical capabilities encompass the complete spectrum of oligonucleotide chemistry, supported by advanced purification technologies and comprehensive analytical methods that ensure product quality and structural integrity.
Quality Assurance
Quality is embedded in every step of our process through a rigorous management system that exceeds industry standards. Each synthesis undergoes extensive analytical characterization using validated methods, from HPLC and mass spectrometry to sequence verification. Our multi-step quality control process, coupled with comprehensive batch documentation, ensures exceptional batch-to-batch consistency and full traceability.
Development & Scale-up
Expertise We excel in translating your requirements from concept to commercial scale, leveraging our deep expertise in process optimization and scale-up strategies. Our proven track record in handling complex sequences and modifications, combined with gram to kilogram manufacturing capabilities, ensures a seamless transition through all development phases while maintaining product quality and consistency.
Comprehensive Support
Your project benefits from our dedicated project management team and experienced technical staff who provide expert consultation throughout the entire process. From customized synthesis strategy development to post-delivery support, we ensure clear communication, regular progress updates, and detailed documentation, making complex projects straightforward and manageable.
Delivery & Timeline
We understand the critical nature of research and development timelines. Our flexible production capacity accommodates various batch sizes and urgent requirements, supported by reliable delivery systems including temperature-controlled worldwide shipping. Whether it's standard synthesis or rush orders, we consistently meet delivery commitments while maintaining our quality standards.
FREQUENTLY ASKED QUESTIONS
What information do I need to provide when submitting a sequence for oligonucleotide synthesis?
For optimal synthesis results, we require comprehensive sequence specifications including the sequence in 5' to 3' direction, desired scale, required modifications (if any), and purity requirements. Additionally, providing your intended application, preferred QC methods (such as HPLC, MS, or PAGE), purification requirements, formulation preferences (salt form, solution or lyophilized), and any special handling requirements will enable us to optimize the synthesis strategy for your specific needs. Our online submission system guides you through all necessary specifications, and our technical team is available for consultation on complex sequences or special requirements.
What is your production scale range, and what information do I need to provide for large-scale synthesis?
Our synthesis capabilities span from milligram to kilogram scales, with a systematic approach to large-scale production (>10g) that typically begins with a pilot batch to optimize synthesis parameters and establish process reproducibility. For large-scale projects, we require detailed information including target scale, purity specifications, regulatory requirements (GMP/non-GMP), final formulation specifications, stability requirements, quality control specifications, and timeline requirements. Our scale-up team works closely with you to develop a customized production strategy, including process optimization, analytical method validation, and stability testing protocols, ensuring a smooth transition from development to large-scale manufacturing.
How do you ensure the quality and purity of the synthesized oligonucleotides?
Every synthesized oligonucleotide undergoes a rigorous quality control process incorporating multiple analytical methods, including HPLC/UPLC analysis for purity assessment and impurity profiling, mass spectrometry (ESI-MS, MALDI-TOF) for identity confirmation, UV spectrophotometry for accurate quantification, and additional specific analyses for modified oligonucleotides to verify modification incorporation and position. Each batch is accompanied by a comprehensive Certificate of Analysis containing detailed analytical data, including chromatograms, mass spectra, and other relevant quality metrics, ensuring full transparency and documentation of product quality.
How do you help customers select the optimal modifications and purification methods for their specific applications?
Our recommendation process begins with a thorough analysis of your application requirements, including target interaction, cellular uptake needs, stability requirements, and environmental conditions. For modifications, we consider factors such as sequence position effects, combination compatibility, and scale-up implications to suggest the most cost-effective solution. Regarding purification, we evaluate multiple methods (HPLC, PAGE, cartridge) based on sequence length, modifications, scale, and purity requirements to determine the optimal approach. Through technical consultation, we provide comparative data from similar projects, discuss potential challenges, and outline cost-benefit analyses for different strategies. This systematic approach ensures that you receive the most suitable technical solution while maintaining a balance between performance and cost-effectiveness.
Can you help with sequence optimization and modification selection for my specific application?
Our technical support team provides comprehensive consultation on sequence design optimization and modification selection, leveraging our extensive experience to enhance nuclease resistance, target affinity, cellular uptake, and pharmacokinetic properties for your specific application. We evaluate your requirements holistically, considering factors such as stability needs, purification methods, analytical testing strategies, and potential scale-up requirements, providing detailed recommendations based on similar successful projects. Early engagement with our technical team can significantly improve project outcomes and help anticipate and address potential challenges before they arise during synthesis and scale-up processes.
RESOURCES
Use the resources in our library to help you understand your options and make critical decisions for your study.
RELATED SECTIONS
Reference
- Roy, Subhadeep, and Marvin Caruthers. "Synthesis of DNA/RNA and their analogs via phosphoramidite and H-phosphonate chemistries." Molecules 18.11 (2013): 14268-14284. Distributed under Open Access license CC BY 4.0, without modification.
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