Therapeutic Oligonucleotides
Supporting antisense, siRNA, aptamer and more from discovery through preclinical development
Scalable oligonucleotide synthesis from micromole to millimole scale
- Extensive backbone, sugar and conjugate modification capabilities
- Tailored purification and analytical support
- UK-based, ISO 9001 certified laboratory
Development Stages
Therapeutic Modalities
Supporting a range of therapeutic oligo modalities and delivery strategies
Therapeutic Development Support
Therapeutic oligonucleotide projects often require advanced modifications, demanding purity specifications and tailored analytical methods.
ATDBio combines scalable synthesis, tailored purification and analytical expertise to support even the most demanding projects.
For more than 20 years, we have supplied oligonucleotides to pharmaceutical, biotechnology and research organisations worldwide.
Extensive Modification Capabilities
Therapeutic oligos often require specialised chemistries to improve stability, potency, delivery and overall performance. ATDBio supports a wide range of established and emerging modification strategies, helping developers tailor oligos to the specific requirements of their project.
Sugar modifications
Common sugar modifications for therapeutic oligonucleotides include RNA, 2′–methoxy (2′–OMe) RNA, 2′–F RNA, 2′–methoxyethyl (2′–MOE) RNA, LNA and constrained ethyl (cEt), in addition to standard DNA.
Backbone modifications
Common backbone modifications include phosphorothioate (PS), phosphorodithioate (PDS), methylphosphonate (MeP), phosphoramidates (PA) and mesyl phosphoramidate (MsPA), in addition to the standard phosphodiester (PO) DNA backbone.
5′– and 3′–modifications
Common 5′– and 3′–modifications in therapeutic oligonucleotides include 5′–(E)–vinylphosphonate (5′–(E)–VP), a metabolically stable phosphate mimic that improves the in vivo stability and potency of siRNAs.
Lipophilic modifications (including 5′–cholesterol and 5′–palmitate) for improved cellular uptake.
GalNAc
A range of off-the-shelf and custom trivalent 5′– and 3′–GalNAc (N-acetylgalactosamine) modifications enable targeted delivery of ASOs and siRNAs to the liver.
Tailored purification and rigorous analysis
Starting from industry best practices, we develop tailored in-house purification and analysis processes to suit each molecule, to meet purity specifications and maximise yield.
Purification
- Reverse phase HPLC
- Ion exchange HPLC
- PAGE
Desalting
- Precipitation
- Gel filtration
- TFF
Analysis
- UPLC/MS
- Capillary electrophoresis
- Non-denaturing UPLC for siRNA duplex purity measurement
Example (right): UPLC trace of a purified 20-mer gapmer antisense oligonucleotide (ASO) containing multiple backbone modifications, and DNA and LNA sugars, showing 94% purity. UPLC analysis conducted using a shallow gradient optimized for the separation of impurities.
Quality and reliability as standard
Our laboratory is based in the UK and is ISO 9001 certified. We strive for the highest possible purity standards, using methods and processes optimized for particular chemistries. We've been making oligonucleotides for some of the world's most important pharma and biotech companies for 20 years, and take pleasure in surpassing our customers' expectations.
Your partner for therapeutic oligonucleotide synthesis.
Contact us