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.

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Custom Oligonucleotide Synthesis & Modification Services
WHAT WE DO? HOW WE DO? SYNTHESIS PLATFORMS WHY CHOOSE US? FREQUENTLY ASKED QUESTIONS RESOURCES RELATED SECTIONS

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

Oligonucleotide Type Characteristics Applications
miRNA
  • 21-23 nucleotides in length
  • Single-stranded non-coding RNA
  • Often contains stem-loop structure
  • High sequence conservation across species
  • Gene expression regulation
  • Cancer research
  • Drug development
  • Biomarker discovery
  • Disease mechanism studies
miRNA Inhibitor
  • Chemically modified antisense oligonucleotides
  • Complementary to target miRNA
  • Enhanced stability and binding affinity
  • Various modifications (2'-O-Me, LNA, etc.)
  • miRNA function studies
  • Therapeutic development
  • Pathway analysis
  • Disease treatment
  • Gene regulation research
siRNA
  • 20-25 base pairs double-stranded RNA
  • Perfect sequence complementarity
  • 3' dinucleotide overhangs
  • Specific target recognition
  • Gene silencing
  • Functional genomics
  • Drug target validation
  • Therapeutic applications
  • Disease treatment
ssRNA
  • Single-stranded RNA molecule
  • Variable length (20-1000+ nt)
  • Can form secondary structures
  • Customizable modifications
  • Molecular biology research
  • Gene expression studies
  • RNA structure analysis
  • Probe development
  • Diagnostic applications
mRNA
  • 5' cap structure
  • Coding sequence
  • 3' poly(A) tail
  • UTR regions
  • Codon-optimized sequences
  • Vaccine development
  • Protein expression
  • Cell therapy
  • Gene therapy
  • Drug development
Bridged Nucleic Acid
  • Locked nucleic acid structure
  • Enhanced thermal stability
  • Increased binding affinity
  • Nuclease resistance
  • PCR applications
  • Diagnostic probes
  • Therapeutic oligonucleotides
  • Gene detection
  • Drug development
RNA Longmer
  • Length >50 nucleotides
  • Complex secondary structures
  • High purity requirements
  • Special synthesis considerations
  • RNA structure studies
  • Long non-coding RNA research
  • Functional RNA studies
  • RNA-protein interaction studies
  • Regulatory RNA research
Plate Oligonucleotide
  • High-throughput format
  • Standardized quality control
  • Multiple sequences per plate
  • Various scale options
  • High-throughput screening
  • Primer libraries
  • SNP analysis
  • Genetic testing
  • Array applications
Degenerated Oligo
  • Mixed base positions
  • Multiple sequence variants
  • Controlled nucleotide ratios
  • Random sequence regions
  • Primer design
  • Library construction
  • Evolution studies
  • Protein binding studies
  • Sequence optimization
Circular Oligonucleotide
  • Covalently closed structure
  • Enhanced nuclease resistance
  • Specific topology
  • Specialized end modifications
  • Rolling circle amplification
  • Nanotechnology
  • Biosensor development
  • Structural studies
  • Enzyme substrate development
Antisense Oligonucleotide
  • Complementary to target RNA
  • Chemical modifications for stability
  • Optimized length (13-25 nt)
  • Enhanced cellular uptake
  • Target validation
  • Therapeutic applications
  • Target validation
  • Therapeutic 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
  • 5-Methylcytidine
  • 5-Methyl-Deoxycytidine (5-M-Dc)
  • MOE-5-Methyl-Cytidine
  • 2,6-Diaminopurine
  • 5-Bromouracil
  • 5-Iodouracil
  • N6-Methyl-dA
  • 2-Aminopurine
  • Pseudouridine
  • Abasic RNA
  • 2'-O-Methyl (2'-OMe)
  • 2'-O-Methoxyethyl (MOE)
  • 2'-Fluoro (2'-F)
  • 2'-Deoxy bases
  • 2'-F-arabinonucleic acid (2'-F-ANA)
  • Bridged Nucleic Acid (BNA)
  • 2'-O-TBDMS
  • ENA (2'-O,4'-C-ethylene-BNA)
  • UNA (Unlocked Nucleic Acid)
  • 2'-Azido modifications
  • Phosphorothioate (PS)
  • Peptide Nucleic Acid (PNA)
  • 5' Thiophosphate
  • Methylphosphonate
  • Morpholino
  • Phosphoramidate
  • 5'-Fluorescein (Fl)
  • 5'-Cholesterol (Chl)
  • 3'-Cholesterol (3'-Chl)
  • 3'TEG-Cholesterol (TEG-Chl-3')
  • Amino modifiers
  • Biotin
  • 5'/3' Phosphate
  • 5'/3' Amino
  • 3' Spacer C3
  • 3' Inverted dT
  • Thiol modifiers
  • N-acetyl-galactosamine (GalNAc)
  • DBCO (Dibenzocyclooctyne)
  • Fluorescent Dyes: FAM/Cy3/Cy5/HEX/TET/TAMRA
  • Quenchers
  • Folate
  • PEG linkers
  • Tocopherol
  • Antibody
  • Peptide
  • Aptamer

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.

Approach for oligonucleotide synthesis. 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
Consultation & Design
Sequence Optimization

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
Chemical Modifications
Synthesis & Purification

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
Quality Control & Validation
Delivery & Support

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.

"For our antisense oligonucleotide project targeting rare diseases, we required multi-site PS modifications and special GalNAc conjugation. The team not only provided comprehensive consultation on modification strategy but also successfully developed a scalable synthesis process. Most impressively, they optimized the purification method to achieve >95% purity at gram scale, which exceeded our expectations. Their experience with regulatory requirements and ability to provide thorough CMC documentation has been instrumental in advancing our IND preparation."

— Dr. James W.

"When we encountered challenges with our long RNA synthesis (95-mer) containing multiple 2'-F modifications, their technical team provided valuable insights for sequence optimization and purification strategy. The ability to receive comprehensive analytical data, including detailed MS and HPLC analysis for each batch, has been invaluable for our research program. Their rapid response to our technical queries and flexible synthesis scale options have made them our preferred partner."

— Dr. Michael S.

" As a diagnostic company, consistent quality across multiple batches of modified probe sequences is critical for our assay development. Their team has consistently delivered high-purity oligonucleotides with precise incorporation of our required fluorescent labels and quencher modifications. The detailed CoA and thorough QC documentation have greatly facilitated our regulatory submission process. "

— Dr. Laura M.

"For our antisense oligonucleotide project targeting rare diseases, we required multi-site PS modifications and special GalNAc conjugation. The team not only provided comprehensive consultation on modification strategy but also successfully developed a scalable synthesis process. Most impressively, they optimized the purification method to achieve >95% purity at gram scale, which exceeded our expectations. Their experience with regulatory requirements and ability to provide thorough CMC documentation has been instrumental in advancing our IND preparation."

— Dr. James W.

"When we encountered challenges with our long RNA synthesis (95-mer) containing multiple 2'-F modifications, their technical team provided valuable insights for sequence optimization and purification strategy. The ability to receive comprehensive analytical data, including detailed MS and HPLC analysis for each batch, has been invaluable for our research program. Their rapid response to our technical queries and flexible synthesis scale options have made them our preferred partner."

— Dr. Michael S.

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Oligonucleotide Specifications

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