Therapeutic oligonucleotides

Antisense oligonucleotides, siRNA oligonucleotides, aptamers and more

We can support your therapeutic oligo project from discovery through to preclinical stage.

Oligonucleotide synthesis from (microgram) scale, for initial discovery and screening, through scale-up (micromole scale), all the way up to millimole scale for preclinical/toxicological studies.

discovery
Synthesis scale
0.2 – 1 µmol
Mass delivered
0.1 – 5 mg
Lead time (estimate)
1 – 4 weeks
optimization
Synthesis scale
10 – 50 µmol
Mass delivered
5 mg – 250 mg
Lead time (estimate)
2 – 6 weeks
preclinical
Synthesis scale
200 µmol – 1 mmol+
Mass delivered
100 mg – 2 g+
Lead time (estimate)
3 – 12 weeks

A wide range of sugar, backbone and 5′– and 3′– modifications — from established to experimental.

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.

Sugar modifications: DNA, RNA
Sugar modifications: DNA, RNA

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.

5′–vinylphosphonate oligonucleotide modification

Lipophilic modifications (including 5′–cholesterol and 5′–palmitate) for improved cellular uptake.

Palmitate oligonucleotide modification
Cholesterol oligonucleotide modification

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.

3′ Long trebler with 3 × GalNAc C3
3′-GalNAc oligonucleotide modification

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
Sugar modifications: DNA, RNA
Example: 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.X

Quality and reliability as standard

Our laboratories are based in the UK and are 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