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Large-scale Oligonucleotide — Milligrams to 100+ Grams

High-quality large-scale oligonucleotide synthesis with advanced modifications from milligrams to 100+ grams. Rigorous QC documentation to accelerating programs from discovery to clinic.

Overview

ISO 9001:2015 / ISO13485:2016 45+ Years of Expertise U.S.A. Facilities-Texas GLP/GMP-Aligned Process-driven scale-up Fit-for-purpose QC

Large-scale oligonucleotide synthesis is the production of DNA and RNA oligos at milligram to multi-gram quantities for research, diagnostic, industrial, and therapeutic applications. Compared with small-scale oligo synthesis, large-scale manufacturing requires optimized chemistry, scalable purification, and strict quality control to ensure consistency and reproducibility.

Bio-Synthesis provides large-scale DNA and RNA oligonucleotide manufacturing with flexible scale-up, advanced modification capabilities, conjugation options, purification, and full analytical QC support — enabling transition from discovery and feasibility through preclinical and therapeutic development programs.

What you can configure

How Large-Scale Oligonucleotide Synthesis Works

Large-scale oligonucleotide synthesis involves sequence design, feasibility assessment, process scale-up, controlled manufacturing, and analytical QC release. Scaling from milligram to gram quantities requires optimization of synthesis chemistry, purification strategy, and impurity control to ensure reproducibility and batch consistency.

When Is Large-Scale Oligonucleotide Synthesis Needed?

  • Therapeutic development such as ASO and siRNA
  • Preclinical and clinical supply
  • Diagnostic manufacturing and assay production
  • NGS workflows and sequencing applications
  • Bulk or OEM oligonucleotide supply

Large-scale oligo programs can be configured by oligo type, sequence length, chemistry, chemical modification pattern, conjugation strategy, purification grade, delivery format, scale, documentation, and QC requirements. Production ranges from milligram research batches to gram, multi-gram, and 100+ gram manufacturing for qualified programs.

Scale-up oligonucleotide synthesis workflow

This workflow outlines key stages of large-scale oligonucleotide synthesis, from sequence evaluation through scale-up, manufacturing, and QC release.

Scale

100 g+

Large-batch capability for qualified DNA/RNA projects

Oligo types

DNA / RNA

ASO, siRNA, primers, probes, modified oligos

Chemistry

Modified

PS, PN, 2′-OMe, 2′-F, LNA/BNA, Morpholino and conjugates

QC

QC & Documentation

Purity and impurity control, identity, CoA, traceability for reulatory pathway planning

Large-Scale vs Small-Scale Oligonucleotide Synthesis

Small-scale oligo synthesis is typically used for early research and screening. Large-scale production is designed for projects that require higher mass, controlled purification, batch reproducibility, and more extensive documentation.

Feature Small-scale synthesis Large-scale synthesis
Typical production scale nmol to mg mg to gram, multi-gram, and 100+ g batches
Common application Discovery, screening, assay setup Therapeutics, diagnostics, manufacturing, validation lots, long-term supply
Purification need Desalting or standard HPLC HPLC, dual HPLC, PAGE, diafiltration, ion-exchange, or project-specific purification
QC expectation Basic identity and purity Advanced analytical QC, CoA, traceability, optional endotoxin, bioburden, residuals, and stability support
Documentation Standard lot documentation Expanded documentation, batch records, regulatory-aligned support, and custom release packages

Manufacturing Capabilities

At Bio-Synthesis, our manufacturing platform is designed to support projects ranging from milligrams to 100+ grams of DNA and RNA oligonucleotides. We combine high-throughput instrumentation, diverse chemistry portfolios, and GMP-aligned workflows to ensure consistent quality at every scale.

Flexible Scale-Up

Research-grade to cGMP with consistent chemistry and documentation.

  • mg to 100+ g lots for DNA/RNA projects
  • Single-strand, duplex, and triplex DNA or RNA oligomers
  • Batch-to-batch reproducibility

*Sequence-dependent capability.

Advanced Modifications

Chemistries for stability, delivery, and function.

  • Backbone: PS, PN, methylphosphonate
  • Sugar: 2′-OMe, 2′-F, LNA/BNA, 2′-MOE, cEt, FANA
  • Conjugates: GalNAc, lipid, PEG, dyes, biotin
  • Formulation support: nanoparticle / LNP formulation

Rigorous QC & Documentation

Regulatory-ready data packages.

  • HPLC or PAGE purification
  • ESI-MS or LC-MS confirmation
  • CoA, traceability, and stability data
  • Custom regulatory reports on request
Category Options Typical Scale Purification QC Package
DNA Oligos Standard, long / Ultramer, primers / adapters, barcoded oligos 100 mg → 100+ g Desalt, HPLC, dual HPLC, diafiltration ESI-MS or LC-MS, duplex ratio, optional endotoxin, bioburden, sodium content, MEV-UV assay, residual chemical analysis, and additional custom testing
RNA Oligos 2′-OMe / 2′-F, capped ends, duplexes / siRNA 100 mg → 100+ g Desalt, HPLC, dual HPLC, diafiltration ESI-MS or LC-MS, duplex ratio, optional endotoxin, bioburden, sodium content, MEV-UV assay, residual chemical analysis, and additional custom testing
Therapeutic-Grade ASO / siRNA Gapmers, splice modulators, conjugated siRNA 100 mg → 100+ g HPLC (RP / ion-pair / AX) Full CoA, impurity profile, ID / assay, moisture
Conjugates & Specialty Oligos GalNAc, lipid, PEG, dyes, biotin; peptide / antibody coupling 100 mg → 100+ g Affinity / RP-HPLC, desalting Conjugation ratio, free linker / dye, residuals

Optional tests: endotoxin, bioburden, residual solvent, heavy metals, and custom analytical methods are available on request.

Oligonucleotide Modifications and Conjugation Options

Large-scale oligonucleotide projects often require chemical modifications to improve nuclease resistance, binding affinity, delivery, detection, or biological performance. Bio-Synthesis supports a broad range of modification and conjugation strategies for DNA and RNA oligos.

Modification category Examples Purpose
Backbone modifications Phosphorothioate (PS), phosphoramidate, methylphosphonate, specialty linkages Improve nuclease resistance, durability, and biological behavior.
Sugar modifications 2′-OMe, 2′-F, LNA/BNA, 2′-MOE, cEt, FANA Enhance stability, affinity, potency, and in vivo performance.
Terminal modifications 5′ phosphate, 3′ blockers, inverted dT, spacer C3, protected ends Protect ends, control activity, and support specialized applications.
Labels and tags FAM, Cy3, Cy5, TAMRA, biotin, digoxigenin, affinity tags Support imaging, detection, affinity capture, and assay workflows.
Reactive handles Amine, thiol, azide, alkyne, DBCO, BCN, maleimide-compatible designs Enable downstream conjugation to proteins, peptides, ligands, surfaces, or carriers.
Delivery conjugates GalNAc, cholesterol, lipids, PEG, peptides, small molecules, ligand systems Improve targeting, uptake, formulation compatibility, and delivery strategy.

Purification, Quality Control, and Documentation

Purification Options

Purification strategy is selected based on oligo length, chemistry, scale, conjugation, intended use, and required purity.

  • Desalting for early-stage and bulk research applications
  • Reverse-phase HPLC and ion-exchange HPLC
  • Dual HPLC for higher-purity requirements
  • PAGE purification for selected complex oligos
  • Diafiltration and buffer exchange on request

Analytical QC and Release Testing

QC packages can be configured to support RUO, GLP-aligned, or cGMP-oriented development workflows.

  • LC-MS / ESI-MS mass confirmation
  • Analytical HPLC purity assessment
  • UV / OD260 quantitation
  • CoA and lot traceability
  • Optional endotoxin, bioburden, residual solvent, heavy metals, water content, sodium content, or custom methods

Quality-focused scale-up

Large-scale oligo manufacturing requires more than simply increasing batch size. Each scale-up program should evaluate synthesis yield, impurity profile, purification method, analytical release criteria, storage conditions, and documentation expectations before moving into routine supply or development-stage production.

Applications of Large-Scale Oligonucleotides

RNA Therapeutics

Support for siRNA, ASO, gapmer, splice-switching oligo, modified RNA, and conjugated oligonucleotide programs.

Molecular Diagnostics

Large-scale primers, probes, molecular beacons, FRET probes, adapters, barcoded oligos, and assay components.

NGS and Sequencing

Indexed primers, adapters, capture probes, UDI libraries, and sequencing workflow oligos.

Gene Editing and CRISPR

Guide RNAs, donor oligos, capture probes, and specialty oligos for genome editing and synthetic biology workflows.

Industrial and OEM Supply

Bulk oligo supply, private-label support, OEM labeling, long-term supply agreements, and custom packaging.

Research to Development

Scale-up support from feasibility batches to larger development lots with expanded documentation and QC.

Process, Quality & Compliance

Large-scale oligonucleotide manufacturing requires controlled processes, validated workflows, and rigorous quality systems. Bio-Synthesis supports projects from research-grade synthesis through development-stage and cGMP-oriented production with full traceability and documentation.

oligonucleotide therapeutic development journey from R and D through analytical development preclinical clinical RUO and cGMP support

Scalable workflow from research to development and clinical support.

Process Control

  • Validated synthesis workflows
  • Controlled scale-up procedures
  • Batch reproducibility

Quality Systems

  • ISO 9001 & ISO 13485
  • GLP-aligned processes
  • Full CoA and traceability

Compliance Support

  • RUO to cGMP transition
  • Documentation packages
  • Audit-ready manufacturing

End-to-End Quality & Scale-Up Support

  • Scalable synthesis from milligrams to 100+ grams
  • ISO 9001:2015 and ISO 13485:2016 quality systems
  • GLP-aligned and cGMP-oriented manufacturing support
  • Comprehensive analytical QC documentation
  • Traceability from raw materials to finished product
  • Built for scale, precision, traceability, and regulatory confidence

Built for Reliable Scale-Up

Bio-Synthesis supports large-scale oligonucleotide programs with chemistry expertise, flexible project configuration, manufacturing experience, and documentation designed to support reproducibility and long-term supply.

From feasibility and pilot batches through development-scale production, our team helps align synthesis, purification, QC, and documentation with your application requirements.

FAQ

What purification methods are available?
Purification options may include desalting, reverse-phase HPLC, ion-exchange HPLC, dual HPLC, PAGE, diafiltration, buffer exchange, or custom purification workflows depending on product requirements.
What scale can Bio-Synthesis produce?
Production can range from milligram quantities to gram, multi-gram, and 100+ gram batches depending on sequence, length, chemistry, modification pattern, purification, and QC requirements.
Can you manufacture both DNA and RNA oligos?
Yes. Large-scale DNA and RNA oligonucleotide synthesis is available, including primers, probes, ASOs, siRNA, modified RNA, modified DNA, specialty oligos, and conjugated constructs.
What modifications are available for large-scale oligos?
Options can include phosphorothioate linkages, 2′-OMe, 2′-F, LNA/BNA, 2′-MOE, terminal modifications, fluorophores, biotin, GalNAc, lipid, PEG, peptide conjugates, and other specialty chemistries.
What is large-scale oligonucleotide synthesis?
Large-scale oligonucleotide synthesis is production of DNA or RNA oligos at milligram, gram, multi-gram, or 100+ gram scale for research, diagnostics, therapeutic development, and manufacturing applications.
What QC is included?
QC can include analytical HPLC, LC-MS or ESI-MS, OD260 quantitation, CoA, lot traceability, and optional endotoxin, bioburden, residual solvent, heavy metals, water content, sodium content, or project-specific methods.
Do you support GMP oligo programs?
Yes. RUO, GLP-aligned, and cGMP-oriented support may be available depending on project scope, documentation requirements, quality expectations, and regulatory needs.
What information is needed for a quote?
Useful information includes sequence, oligo type, length, scale, modifications, conjugation needs, purification method, QC requirements, buffer or salt form, delivery format, timeline, and intended application.

How to Order Large-Scale Oligonucleotides

To request a large-scale oligonucleotide quote, provide the sequence, oligo type, desired scale, modification requirements, purification method, QC expectations, and intended application. If the final configuration is not yet defined, our team can help review feasibility, scale-up strategy, and documentation needs.

Project Information to Provide

  1. Oligo type: DNA, RNA, ASO, siRNA, primer, probe, adapter, guide RNA, or specialty oligo.
  2. Sequence and length: final sequence, target length, strand format, duplex/triplex needs, or candidate design.
  3. Scale: mg, gram, multi-gram, or 100+ gram target batch size.
  4. Modifications: backbone, sugar, terminal, label, linker, reactive handle, or delivery conjugate requirements.
  5. Purification: desalt, HPLC, dual HPLC, PAGE, diafiltration, buffer exchange, or custom purification.
  6. QC and documentation: MS, HPLC, OD260, CoA, endotoxin, bioburden, residuals, stability, or regulatory-aligned documentation.

Scale-Up Support Available

If your program is moving from small-scale synthesis to development or manufacturing scale, Bio-Synthesis can help evaluate:

  • Sequence and chemistry feasibility
  • Impurity profile and purification strategy
  • Batch size and staged production plan
  • Analytical QC and release testing needs
  • Salt form, buffer exchange, and packaging
  • Documentation and traceability requirements
  • RUO, GLP-aligned, or cGMP-oriented support path

Why Choose Bio-Synthesis

Trusted by biotech leaders worldwide for over 45+ years of delivering high quality, fast and scalable synthetic biology solutions.