KATIE MURRAY¹, ANDREW LIVINGSTON²
1. Medicines Manufacturing Innovation Centre, CPI, United Kingdom 
2. Exactmer, United Kingdom

Abstract

Oligonucleotides, which have already shown success in the treatment of rare diseases, are now being used to treat conditions with much larger patient populations. However, limitations associated with the current state-of-the-art solid-phase manufacturing technology – namely high costs and low capacity – inhibit their true potential. Despite this, oligonucleotide-based drugs are still moving through the R&D pipeline, but their progress will be hindered without an overhaul of the current manufacturing process. An exciting academic, government and industry collaboration is investigating the potential of a novel liquid-phase synthesis technique. This technique – referred to as Nanostar Sieving – circumvents many of the limitations associated with solid-phase oligonucleotide manufacturing, offering a more cost-effective and environmentally sustainable method of manufacturing oligonucleotides at a larger scale.

Oligonucleotide-based therapeutics represent a new class of medicines with the potential to treat a wide range of diseases. By interfering with how genes are expressed, these short nucleic acid polymers can enable more precision and a more personalised medicine approach, as they can theoretically target any gene with minimal, or predictable, off-target effects (1).

While this class of medicines is still relatively new, as of January 2020 ten oligonucleotide drugs had received regulatory approval from the FDA (1) and their potential is growing. Up until now the majority of these medicines have focused on the treatment of rare diseases with smaller patient groups, but developers are looking to expand their portfolio. Oligonucleotides are now being explored to treat chronic diseases that affect much larger patient populations. For instance inclisiran, a cholesterol lowering drug, was approved for use in the EU in December 2020 and represents an opportunity for a much wider population to benefit from these novel medicines (2).

With more and more oligonucleotide-based medicines moving through the R&D pipeline, including over 135 alrea ...