Login / Register Order My Items
mob-logo
Contact Us
800.227.0627
Contact Us Quote Order Login / Register

Oligonucleotide Process Development Services

Process development for custom DNA, RNA and modified oligonucleotides from feasibility review and pilot synthesis through purification optimization, scale-up, analytical methods, formulation readiness and tech-transfer documentation.

45+ Years of Expertise ISO 9001:2015 / ISO 13485:2016 Bench to Kilo Scale Confidential & IP-Protected U.S.A Facilities - Texas
Request a Development Plan View Development Areas
Talk to a chemist Request a quote
Overview At a Glance Development Areas Purification Analytics Deliverables FAQ Contact

Overview

Custom oligonucleotide process development helps transform a sequence or chemistry concept into a reproducible production workflow. The process must balance synthesis efficiency, purification strategy, analytical control, scalability, yield, purity and documentation level.

Bio-Synthesis supports DNA, RNA, LNA/BNA, PNA, Morpholino, ASO, siRNA, gapmer and mixed-backbone oligonucleotide programs, including difficult sequences, rare monomers, conjugates, labels and specialized modifications.

Development scope can be configured for RUO, diagnostic, ISO13485, GLP or cGMP-oriented workflows depending on intended use, target scale and documentation requirements.

Development Scope

Technical Coverage

A practical view of the major workstreams used to build a scalable oligo process.

Design & Feasibility

Sequence review, chemistry risk assessment, monomer availability and modification strategy.

Synthesis & Screening

Small-scale pilot runs, coupling optimization, sulfurization or oxidation tuning and early QC feedback.

Purification & Recovery

RP-HPLC, IP-RP-HPLC, IEX, PAGE and yield-versus-purity optimization.

Scale-Up & Transfer

Process parameters, in-process controls, analytical methods and tech-transfer documentation.

Process Development at a Glance

Quick View

A compact view of what Bio-Synthesis can coordinate across development and manufacturing readiness.

01

Complex Oligo Chemistry

DNA, RNA, LNA/BNA, PNA, Morpholino, PS, dyes, lipids, GalNAc, PEG and mixed formats.

02

Data-Driven Pilot Work

HPLC, CE, LC-MS, UV and crude-profile feedback guide process decisions.

03

Scale-Aware Optimization

Route decisions consider prep columns, cycle time, solvent use, recovery and reproducibility.

04

Documentation Ready

Support can include CoA data, method summaries, batch records and tech-transfer packages.

Core Development Areas

This section combines the key technical capabilities and project stages into four practical workstreams, so users can quickly understand how Bio-Synthesis supports oligo process development from feasibility through scale-up.

Feasibility

Sequence, Chemistry & Risk Review

  • Base, backbone and modification strategy review
  • Length, GC content, Tm and secondary-structure considerations
  • Rare monomer, custom linker or conjugation feasibility
  • Low-yield step, sensitive linker and scale-risk assessment
Pilot

Pilot Synthesis & Screening

  • Small-scale automated solid-phase synthesis screening
  • Coupling time, activator, capping and sulfurization optimization
  • Early integration of non-standard bases, dyes and linkers
  • Crude HPLC/CE, LC-MS identity and UV quantitation feedback
Purification

Purification Route Optimization

  • RP-HPLC, IP-RP-HPLC, IEX and PAGE route screening
  • Shortmer, n-1/n-2, deprotection by-product and salt removal
  • Yield-versus-purity trade-off evaluation
  • Gradient, buffer and solvent strategy scalable to prep workflows
Scale-Up

Scale-Up, Analytics & Documentation

  • Column loading, flow rate, reagent use and throughput planning
  • In-process controls and analytical method development
  • Formulation readiness, lyophilization and stability support
  • Batch records, specifications and tech-transfer documentation

Purification Strategy Selection

Purification is often the key decision point in oligonucleotide process development. The best route depends on length, backbone, charge, hydrophobicity, modification pattern and required purity.

Oligo Type / Challenge Common Development Route Why It Matters
Short DNA or RNA oligos RP-HPLC or IP-RP-HPLC Fast route screening and strong resolution of many truncated products.
PS-rich ASO or gapmer designs IEX or mixed HPLC/IEX strategy Charge-based resolution can help separate related species and backbone variants.
siRNA duplexes Strand purification followed by annealing and duplex QC Controls individual strand quality before duplex formation.
Highly modified or conjugated oligos Customized RP-HPLC, IEX or orthogonal purification Hydrophobic tags, dyes, lipids, PEG or GalNAc can shift retention behavior.
Ultra-high purity requirement PAGE, preparative HPLC or multi-step purification Used when impurity profile or application requires tighter purification control.

Analytical Method & Stability Support

Analytical methods are built into the development workflow so synthesis and purification changes can be measured rather than guessed.

Identity & Purity

Analytical Characterization

  • HPLC / UPLC purity profiles
  • CE and IEX for orthogonal impurity control
  • LC-MS or MALDI identity confirmation
  • UV quantitation and extinction-coefficient checks
Impurity Control

Process-Related Impurities

  • Shortmers, n-1/n-2 species and depurination products
  • Residual salts, solvents and deprotection by-products
  • Charge variants for PS-rich or long oligos
  • Method thresholds aligned to project needs
Stability

Stability-Indicating Methods

  • Accelerated and long-term stability studies
  • Temperature excursion and shipping studies
  • Heat, pH and enzymatic stress conditions
  • Method validation support when required
Formulation

Delivery Readiness

  • TE, PBS or custom buffer formats
  • Liquid vial, lyophilized cake, tube or plate formats
  • Sterile filtration, endotoxin or bioburden as needed
  • Conjugate stability for dyes, peptides, lipids, GalNAc or PEG

Development Deliverables

Deliverables can be scaled from a focused feasibility memo to a fuller process-development and tech-transfer package.

Process Summary

  • Recommended synthesis route
  • Critical process parameters
  • Yield and recovery observations
  • Scale-up risk notes

Analytical Package

  • HPLC/UPLC or CE profiles
  • LC-MS or MALDI identity data
  • Impurity observations
  • Method summary and acceptance criteria

Transfer Support

  • Batch record inputs
  • In-process controls
  • Raw material and reagent considerations
  • Tech-transfer recommendations

How to start: Share sequence or length, chemistry/modifications, target scale, purity goal, intended use, desired QC methods, formulation needs and documentation requirements.

Frequently Asked Questions

FAQ

What is oligonucleotide process development?
It is the optimization of synthesis, purification, analytical methods, scale-up parameters, formulation readiness and documentation so an oligo process can move from feasibility to reproducible production.
Do you provide ICH stability support?
Yes. Accelerated, long-term, shipping and temperature excursion studies can be planned with reports aligned to the intended development or filing context.
What determines whether RP-HPLC or IEX is used?
Hydrophobic modifications and shorter oligos often favor RP-HPLC. Longer or PS-rich designs that differ by charge may resolve better with IEX. Route screening confirms the best method.
Can Bio-Synthesis transfer the process to our site or CMO?
Yes. Bio-Synthesis can prepare process parameters, specifications, in-process controls, analytical methods and documentation for downstream manufacturing transfer.
What QC is standard during process development?
 Analytical HPLC and mass spectrometry identity are commonly used. CE, IEX, UV quantitation, hybridization assays, endotoxin or bioburden may be added based on project needs.
What information is needed to start?
 Send sequence or length, chemistry, modifications, target scale, purity goal, application, analytical methods, formulation or packaging needs and documentation requirements.
More FAQ'sAll FAQ's
PROCESS DEVELOPMENT SUPPORT

Need a Scalable Oligo Development Plan?

Discuss feasibility, pilot synthesis, purification optimization, analytical methods, scale-up, formulation readiness or tech-transfer documentation with our oligonucleotide development team.
Request Development Plan Speak with a Scientist
Need help before quoting?
Email: info@biosyn.com
Phone: 800-227-0627 (US/CAN)
INT: +001-972-420-8505

Related Services

Connect process development with release QC, analytical method development, stability studies and synthesis scale-up.

Release QC Method Development Stability Studies Oligo Synthesis Fill & Finish

Fast Quote Checklist

Include sequence or length, chemistry, modifications, target scale, purity goal, intended use, QC needs and timeline.

Send Project Details →

Why Choose Bio-Synthesis

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

Greetings Researchers,

Please be advised that any information, guidelines, writeups, and oral/video/graphic content on our website are intended solely as general guidelines.
It is the researcher's sole responsibility to conduct thorough research on the designs of the products intended for their experiments before submitting
their designs to Biosynthesis for review of production feasibility.
Thank you for your understanding.

Quick Links