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Large-Scale RNA Synthesis

Scalable RNA oligonucleotide manufacturing with extensive base, 2′ sugar, and backbone modification capabilities, supported by purification, release QC, and process-development expertise.

Core capabilities: modified RNA oligos, siRNA, duplex RNA, guide RNA components, labeled RNA probes, RNA aptamers, purification, release QC, and scale-up support.

modified RNA oligossiRNA & duplex RNAguide RNARNA base modifications2′ sugar modificationsbackbone modificationspurification & release QCscale-up support

Large-Scale RNA Synthesis Overview

Large-scale RNA synthesis is one of Bio-Synthesis’ highest-demand oligonucleotide manufacturing capabilities, supporting increasingly complex RNA programs in therapeutics, diagnostics, gene regulation, gene editing, delivery, and advanced molecular assay development.

Our platform supports standard and highly modified RNA oligonucleotides, including single-stranded RNA, duplex RNA, siRNA, antisense RNA, RNA aptamers, guide RNA components, labeled RNA probes, and conjugation-ready RNA constructs.

Bio-Synthesis has refined RNA synthesis, deprotection, purification, analytical testing, and scale-up workflows to support high-purity RNA manufacturing with reproducible quality and documentation.

At a glance: Bio-Synthesis provides large-scale RNA oligonucleotide synthesis for modified RNA, siRNA, duplex RNA, guide RNA components, RNA aptamers, labeled RNA probes, and conjugation-ready RNA constructs, with purification, release QC, documentation, and scale-up support.
Large-scale RNA synthesis workflow from design and feasibility to scale-up and release

From RNA Design to Large-Scale Production

From RNA Design to Large-Scale Production

  • Design & Feasibility: sequence evaluation, modification strategy, duplex design, and scale planning
  • Synthesis: optimized RNA phosphoramidite chemistry and coupling strategy
  • Deprotection & Handling: RNA-sensitive cleavage, deprotection, and recovery workflows
  • Purification: HPLC, PAGE, IEX, and application-specific purification options
  • Quality Control: LC-MS, HPLC, impurity profiling, duplex assessment, and release testing
  • Documentation & Scale-Up: CoA, batch records, traceability, and transition to larger production
Platform advantage: Bio-Synthesis combines RNA chemistry expertise with scalable manufacturing, purification, release QC, and documentation to support high-value RNA oligonucleotide programs from early development through production.

Why Bio-Synthesis for Large-Scale RNA?

Extensive RNA Modifications

Base, 2′ sugar, backbone, terminal, internal, and conjugation-ready modification options.

Scale & Flexibility

Custom RNA manufacturing from development quantities to larger production lots.

Advanced QC & Documentation

Release QC, CoA, chromatograms, MS reports, and project-specific documentation.

Process Development Support

Feasibility, pilot synthesis, purification optimization, process transfer, and scale-up planning.

Large-Scale RNA Synthesis Platform

RNA oligonucleotides can be engineered at three structural levels: the nucleobase, the ribose sugar, and the internucleotide backbone linkage. Bio-Synthesis provides extensive RNA modification capabilities across all three dimensions to improve stability, activity, binding, nuclease resistance, delivery, and analytical performance.

Large-scale RNA synthesis platform showing RNA base, ribose sugar, and backbone modification sites

RNA can be engineered at the base, sugar, and backbone level to support stability, activity, recognition, and delivery requirements.

RNA Base Engineering

Modified RNA bases can tune immune recognition, pairing behavior, stability, binding, labeling, and biological performance.

RNA Sugar Engineering

2′ sugar modifications are central to RNA stability, nuclease resistance, duplex properties, and therapeutic design.

RNA Backbone Engineering

Backbone linkage modifications can improve nuclease resistance, pharmacology, and compatibility with therapeutic or diagnostic workflows.

Supported RNA Format

Bio-Synthesis supports multiple RNA formats at development and large-scale quantities. Projects can be manufactured as standard RNA, heavily modified RNA, duplex RNA, labeled RNA, or conjugation-ready RNA.

Format Key Features Typical Uses
Single-Stranded RNA Standard or modified RNA oligos with terminal/internal modifications Probes, aptamers, antisense RNA, controls, binding studies
Duplex RNA / siRNA Sense/antisense duplexes, optional overhangs, asymmetric modifications RNAi, gene silencing, screening, therapeutic development
Guide RNA Components crRNA, tracrRNA, sgRNA components, modified guide RNA designs CRISPR and gene-editing workflows
Modified RNA Base, sugar, backbone, terminal, internal, and conjugation-ready modifications Stability enhancement, delivery, diagnostics, therapeutic programs
Labeled RNA Probes Fluorophores, quenchers, affinity tags, spacers, and reactive handles Assays, imaging, detection, hybridization, molecular diagnostics

Large-Scale RNA Synthesis (50 mg to Multi-Gram)

Bio-Synthesis supports large-scale RNA synthesis from 50 mg to multi-gram quantities, including standard and highly modified RNA oligonucleotides. Our platform is optimized for duplex RNA, siRNA, guide RNA components, labeled RNA probes, and complex modified RNA constructs.

Manufacturing scale, yield, and purity are influenced by sequence length, modification type, duplex design, and purification requirements. Each RNA project is evaluated to support optimal synthesis efficiency, recovery, and reproducibility at scale.

The pricing below applies to standard RNA oligonucleotides under defined conditions. For modified RNA, duplex RNA, guide RNA, conjugation-ready RNA, or sequences requiring specialized purification and analytical testing, please contact us or request a custom quote.

Optional services such as advanced purification, analytical testing, release QC, CoA documentation, process development, and scale-up support can be incorporated based on project needs. Learn more in our Purification, Quality Control, and Documentation section.

Transparent pricing for standard RNA. Custom pricing available for advanced RNA designs.

Large-scale RNA projects are processed in an RNase-free environment with configurable purification, QC, formulation, packaging, and documentation options based on the intended application.

Example Pricing: HPLC-Purified Unmodified RNA, 10–30-mer, PO Backbone

Final Amount Price (USD)
50 mg $3,200
100 mg $4,800
250 mg $6,500
500 mg $8,000
1,000 mg $10,500
>1,000 mg Inquire
Representative large-scale RNA lots in bottles and labeled Bio-Synthesis boxes

Representative large-scale RNA lots. Packaging varies by order and project requirements.

Prices are examples for unmodified RNA 10–30 nt and include HPLC purification and diafiltration. Final cost varies with sequence composition, modification pattern, purification requirements, QC testing, formulation, and documentation needs.

Documentation & Supply Agreements
  • Process development under QSR-oriented manufacturing workflows available on request
  • Long-term pricing stability and recurring lot support available through supply agreements
  • Custom documentation packages can include CoA, analytical data, batch records, and release summaries
Need multi-gram RNA or modified RNA?
For modified RNA, duplex RNA, guide RNA components, in vivo processing, or multi-gram supply, please request a custom quote.

RNA Modifications Available at Scale

Extensive RNA modification capabilities across base, sugar, and backbone chemistry

Bio-Synthesis provides extensive RNA modification capabilities, including base modifications, 2′ sugar modifications, backbone modifications, terminal labels, internal labels, spacers, and conjugation-ready functional handles. These modifications are commonly used to improve RNA stability, nuclease resistance, potency, biodistribution, targeting, and assay performance.

Modified RNA Bases

RNA base modifications can influence pairing, immune recognition, translation-related behavior, stability, and molecular recognition.

  • Pseudouridine and related uridine analogs
  • 5-methylcytidine and cytidine analogs
  • N6-methyladenosine and adenine analogs
  • Inosine and hypoxanthine-type analogs
  • Fluorescent, affinity, and reactive base modifications

2′ Sugar Modifications

2′ ribose modifications are among the most important RNA engineering tools for stability and therapeutic performance.

  • 2′-O-methyl RNA
  • 2′-fluoro RNA
  • 2′-O-methoxyethyl-type designs where applicable
  • Locked or constrained nucleic acid analogs
  • Mixed 2′ modification patterns

Backbone Linkages

Backbone modifications help protect RNA from nuclease degradation and tune charge, stability, and biological performance.

  • Phosphorothioate linkages
  • Mixed phosphodiester/phosphorothioate designs
  • Terminal PS protection patterns
  • Custom linkage strategies on request

Terminal Modifications

5′ and 3′ modifications support labeling, stabilization, conjugation, blocking, and delivery-oriented designs.

  • 5′ phosphate, triphosphate, or cap-related designs where applicable
  • 3′ blocking groups and inverted bases
  • Amine, thiol, azide, alkyne, DBCO, and biotin
  • Fluorophores, quenchers, and affinity tags

Internal Labels & Spacers

Internal RNA modifications can support probe design, structure-function studies, and controlled presentation of functional groups.

  • Internal fluorophores and quenchers
  • Internal biotin or affinity tags
  • Spacer arms and abasic-like sites
  • Position-specific reactive handles

Conjugation-Ready RNA

RNA can be synthesized with functional groups for downstream conjugation to ligands, peptides, polymers, lipids, nanoparticles, surfaces, or biomolecules.

  • Amine, thiol, azide, alkyne, DBCO, and NHS-compatible designs
  • Biotin, digoxigenin, and affinity tags
  • Lipid, ligand, and delivery-oriented handles
  • Custom conjugation support available
Modification strategy: RNA performance often depends on the precise combination of base, sugar, and backbone chemistry.

Large-Scale RNA Manufacturing Capabilities & Scale Expertise

Engineered for complex RNA synthesis, scale-up performance, and reproducible manufacturing outcomes.

Large-scale RNA manufacturing requires tight control over synthesis, deprotection, purification, analytical testing, and storage conditions. Bio-Synthesis supports RNA projects from feasibility and pilot production through larger manufacturing requirements.

Flexible RNA Scale

Scalable RNA manufacturing from milligram development batches to multi-gram production with consistent yield and purity.

  • Milligram to gram-scale planning
  • Custom batch-size evaluation
  • Recurring RNA production support

Complex RNA Builds

Support for modified, duplex, labeled, guide, and conjugation-ready RNA constructs where standard workflows are not sufficient.

  • Single-stranded and duplex RNA
  • High-density modification patterns
  • RNA with labels, linkers, and conjugation handles

RNA-Specific Optimization

Projects can be optimized to address RNA sensitivity, impurity formation, duplex behavior, and recovery challenges.

  • Coupling and deprotection strategy review
  • Purification route selection
  • Duplex annealing and characterization planning
Manufacturing focus: RNA scale-up requires RNA-specific chemistry and handling expertise.

Purification, Quality Control, and Documentation

Large-scale RNA quality depends on synthesis efficiency, RNA-sensitive deprotection, nuclease-safe handling, purification, analytical testing, and release documentation.

Purification Options

Purification is selected based on RNA length, modification type, impurity profile, duplex status, scale, and target purity.

  • RP-HPLC or IP-RP-HPLC
  • IEX / charge-based purification
  • PAGE for size-critical RNA separation
  • Dual purification for demanding projects
  • Desalting, buffer exchange, and formulation support

Release QC Testing

QC panels can verify identity, purity, impurity profile, residuals, duplex integrity, and safety-related parameters.

  • Identity by LC-MS, ESI-MS, or MALDI-TOF
  • Purity by HPLC, CE, PAGE, or IEX
  • Impurity profiling for shortmers and variants
  • Duplex confirmation where applicable
  • Endotoxin, bioburden, and residual options

Documentation Package

Documentation can be matched to the customer’s program stage and downstream requirements.

  • Certificate of Analysis (CoA)
  • HPLC chromatograms and MS reports
  • Batch and purification summaries
  • Annealing or duplex documentation where applicable
  • Custom release documentation on request
QC Category Representative Methods Purpose
Identity LC-MS, MALDI-TOF, enzymatic digest mapping Confirm molecular mass and support modified RNA verification.
Purity / Impurities HPLC, CE, PAGE, IEX Quantify full-length RNA, shortmers, and variants.
Duplex / Structure Annealing analysis, native PAGE, thermal or chromatographic assessment Support siRNA, duplex RNA, and guide RNA component quality.
General / Safety UV/OD260, pH, appearance, endotoxin, bioburden, residuals Support release specifications for higher-control workflows.
QC positioning: analytical release testing and documentation help customers qualify RNA for sensitive downstream workflows.

Quality Systems & Compliance Support

RNA Process Development

Complex RNA projects can benefit from early feasibility review, pilot synthesis, purification optimization, duplex evaluation, and analytical-method planning.

  • Sequence and modification feasibility review
  • RNA protecting group, coupling, and deprotection evaluation
  • Pilot synthesis with analytical feedback
  • Purification route optimization
  • Scale-up and recovery risk assessment

Quality & Compliance Support

Quality support can be aligned with intended use, from RUO to diagnostic or therapeutic-development programs.

  • ISO 9001 / ISO 13485 quality-system alignment
  • GLP-oriented documentation where appropriate
  • GMP-supportive release panels and QA oversight
  • ICH Q2(R2)-style method validation support
  • USP/EP-aligned safety and release testing options
Compliance note: the appropriate RNA quality package depends on intended use, regulatory stage, final formulation, and release requirements.

Process Transfer & cGMP Scale-Up Support

Following successful RNA development and pilot-scale production, Bio-Synthesis supports the transition of RNA oligonucleotide projects into larger-scale and regulated manufacturing workflows.

RNA manufacturing pathway from R&D to pilot, GMP, and commercial scale

Our team works closely with customers to ensure that RNA synthesis, purification, duplex handling, and analytical methods are reproducible and transferable from research-scale to production-scale environments. Our goal is to be your long-term RNA manufacturing partner—delivering high-purity RNA oligonucleotides at every stage of your program, with the quality, reliability, and documentation your success depends on.

  • Process transfer: transition of synthesis, deprotection, purification, and annealing workflows to larger-scale production
  • Scale-up optimization: adjustment of reaction conditions, purification, recovery, and formulation
  • Analytical method transfer: consistency in QC testing, impurity tracking, and release criteria
  • Documentation support: batch records, method descriptions, traceability, and CoA documentation
  • cGMP readiness: support for RNA programs requiring higher levels of quality control and regulatory alignment
Scale-up pathway: RNA projects can progress from feasibility and pilot synthesis to larger-scale production, with process control and documentation supporting downstream regulatory or commercial requirements.

Typical RNA Projects We Support

Built for RNA programs that require chemistry depth, scale, quality, and documentation.

siRNA & Duplex RNA

Sense/antisense duplexes, modified strands, overhang designs, and RNAi-focused constructs.

Guide RNA Components

crRNA, tracrRNA, sgRNA components, and modified guide RNA designs for gene-editing workflows.

Modified RNA Therapeutics

RNA designs requiring base, sugar, and backbone modifications for stability, activity, and delivery.

Labeled RNA Probes

Fluorescent, quenched, affinity-tagged, and hybridization-ready RNA probes for diagnostics and assays.

RNA Aptamers

Standard and modified RNA aptamers for binding, targeting, selection, and detection applications.

Conjugation-Ready RNA

RNA containing amine, thiol, azide, alkyne, DBCO, biotin, lipid, ligand, or other reactive handles.

Applications of Large-Scale RNA Synthesis

RNA Therapeutic Development

Modified RNA oligonucleotides for RNAi, antisense, gene regulation, targeting, and delivery research.

siRNA & Duplex RNA

High-purity duplex RNA constructs for gene silencing, screening, and therapeutic-development workflows.

CRISPR Guide RNA

Synthetic guide RNA components and modified guide RNA designs for gene-editing workflows.

RNA Aptamers

Standard and modified RNA aptamers for binding studies, detection, and targeting applications.

Diagnostic RNA Probes

Labeled RNA probes with fluorophores, quenchers, spacers, affinity tags, and hybridization-optimized designs.

Conjugation & Delivery

RNA containing amine, thiol, azide, alkyne, DBCO, biotin, lipid, ligand, or other reactive handles.

FAQ

What types of RNA can Bio-Synthesis make at scale?
Bio-Synthesis can support standard and modified RNA oligonucleotides, including single-stranded RNA, duplex RNA, siRNA, guide RNA components, RNA aptamers, labeled RNA probes, and conjugation-ready RNA constructs.
Can heavily modified RNA be made at large scale?
Yes. Modified RNA can include modified bases, 2′ sugar modifications, backbone linkages, terminal modifications, internal labels, spacers, and conjugation handles.
What RNA modifications are commonly available?
Common RNA modifications include pseudouridine-type bases, 5-methylcytidine, 2′-O-methyl, 2′-fluoro, phosphorothioate linkages, terminal phosphates, fluorophores, quenchers, biotin, and reactive handles.
What purification is recommended for large-scale RNA?
Purification depends on length, format, and application. Options may include HPLC, IEX, PAGE, dual purification, desalting, and buffer exchange.
Can RNA process development support scale-up?
Yes. Projects can include feasibility review, pilot synthesis, deprotection optimization, purification development, analytical method planning, duplex evaluation, and scale-up support.
Is this page for mRNA manufacturing?
This page focuses on synthetic RNA oligonucleotides and modified RNA oligos. For long mRNA or IVT-based workflows, contact Bio-Synthesis to discuss project fit.

Contact & Quote Request

For the fastest response, share your RNA sequence, scale, and modification requirements with our scientific team.

Fast quote checklist

  • Format: ssRNA, duplex RNA, siRNA, guide RNA, aptamer, probe, or conjugation-ready RNA
  • Sequence length, strand design, and quantity required
  • Modification class: base, sugar, backbone, label, spacer, linker, or conjugate handle
  • Modification position: 5′, 3′, internal, strand-specific, or sequence-specific
  • Purification, QC, CoA, release testing, formulation, and delivery requirements

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Why Choose Bio-Synthesis

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