Large-scale oligonucleotide manufacturing

Abstract

In the past decades, synthetic oligonucleotides have been explored for therapeutic purposes and seven oligonucleotide drugs have been successfully approved by FDA with many oligonucleotides, approximately 100, are in clinical trials worldwide. The increase in demand for a large quantity of oligonucleotide material for therapeutic applications has led to more cost-effective manufacturing technologies. Synthetic oligonucleotide quality has been improved by using raw materials with the highest possible purity. At the same time, yields and throughput have been increased significantly by the introduction of high loaded polymer supports like NittoPhase™ and by continuous development and optimization of oligonucleotide manufacturing processes that allow oligonucleotide manufacturers to access to a wide variety of oligonucleotide modifications. However, large scale oligonucleotide manufacturing is still not straight forward. In this chapter, considerations on large scale manufacturing equipment and a small scale modeling approach for scaling up each of the manufacturing processes are described.