Oligonucleotides (ON) synthesized using solid phase chemistry contain various impurities, among which the failure sequences consist of a major portion and are difficult to remove. Known methods for ON purification such as HPLC are expensive. Here we present a new technology to solve the problem. During ON synthesis, either the failure sequences or the full-length sequences are tagged with a polymerizable group. After synthesis, the crude ON is subjected to polymerization, and the failure and success sequences are simply separated by filtration. Other major impurities such as small molecules from protecting groups are removed by n-BuOH precipitation. HPLC analysis indicates that the new methods can give highly pure ON in good to excellent recovery yields. Because these methods do not require any chromatography, consume minimum buffers, and are convenient to use, we expect them to find applications in large scale ON drug purification and high-throughput ON purification.

Purification of synthetic oligodeoxynucleotides using a catching by polymerization approach

245th National Meeting (2013)

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