Almac Sciences extends selectAZyme™ offering to include therapeutic oligonucleotide synthesis

Synthesis leverages new RNAL Ligase (RNAL) enzyme kit, a focussed library of 10 double stranded RNA Ligase enzymes selected from Almac Sciences’ extended RNAL enzyme panel

Almac Sciences, a member of the Almac Group, announces new capability to synthesize therapeutic oligonucleotides, made possible by the introduction of a new an easy-to-use RNA Ligase (RNAL) enzyme kit that extends the company’s selectAZyme^TM enzyme screening collection.

The kit contains a focussed library of 10 double stranded RNA Ligase enzymes, selected from an extended RNAL enzyme panel, and can be used to make single and double stranded RNA— as described in technical paper by Caswell et al. ACS Chem. Biol. 2023, 18(10), 2183-2187.

This marks the first time that Almac’s award-winning enzyme technology has been applied to therapeutic oligonucleotide synthesis, a class of drug that has rapidly grown in interest due to their synthesis and manufacture. Building upon the strong biocatalytic technology base already available at Almac, this newly available synthesis leverages the company’s selectAZyme™ ligase enzymes to produce both single stranded and double stranded oligo products.

The Ligase panel has the following attributes:

• Manufacture of high-quality RNA oligo product using the Almac ligase 3:2:3:2 approach via RNA blockmer assembly,
• Activity against both natural and unnatural nucleosides with modifications including 2’F, 2’MOE & 2’OMe modifications and many more,
• Enzymes can be immobilised and/or provided with low-endotoxin levels on request,
• The enzymes can be used to complement existing oligonucleotide synthesis by combining a biocatalytic approach with existing classical chemical synthesis,

Choosing a complementary biocatalysis route for oligonucleotide synthesis offers many benefits including higher isolated purity of the RNA product, purity enrichment via ligation of the blockmers due to complementarity of base pairing. This technology also allows for convergent synthesis opening up new supply chain opportunities.

Dr Jill Caswell, Biology Senior Team Leader commented “Almac has developed a range of biocatalytic products and services to facilitate the challenges posed in biocatalytic oligonucleotide synthesis and this new RNAL kit has the ability to diversify and strengthen supply chain blockmer manufacture which can often shorten timelines, benefitting our customers greatly. The expansion of our portfolio of product offerings further showcases our commitment to providing our customers with the most innovative and efficient processes.”

The selectAZyme^TM RNA Ligase kit is readily available now and extended panels of double stranded RNA Ligase enzymes are available on request as well as single stranded RNA Ligases.