The Hitchhiker´s Guide To Creating Oligonucleotides From Start To Finish

Scaling up oligonucleotide production—whether for a CDMO or internal demand—requires a precise orchestration of chemical synthesis and downstream processing. This guide, the first in a nine-part series, maps out the complete mid-scale workflow to help labs transition from concept to creation. The process begins with solid-phase synthesis and deprotection, but the complexity increases when ensuring purity through chromatography methods like AEX, IP-RP, and HILIC.

Beyond initial synthesis, successful manufacturing depends on rigorous downstream steps, including tangential flow filtration for desalting and endotoxin removal, culminating in lyophilization. Understanding how these unit operations connect is essential for building an efficient, scalable lab environment. Read the full overview to visualize the complete lifecycle of an oligonucleotide.