Economics of oligonucleotide purification

Raw material costs for production of antisense oligonucleotide drug substances have been reduced more than 97% since 1991 through process optimization, scale-up economies, and reduced raw material costs,1,60 while the manufacturing and control associated labor costs have fallen even more precipitously. Key changes have converted the process from use of costly 

Sanghvi, Y. S., Andrade, M., Deshmukh, R. R., Holmberg, L., Scozzari, A. N., and Cole, D. L. (1999). Chemical synthesis and purification of phosphorothioate antisense oligonucleotides. In Manual of Antisense Methodology (G. Hartman and S. Endres, eds.), pp. 3-23. Kluwer Academic Publishers, New York. 

Sanghvi, Y. S. (1999). DNA with altered backbone in antisense applications. In DNA and Aspects of Molecular Biology (E. T. Kool, ed.), Vol. 7, pp. 285-311. Pergamon, New York. 

Poddenin, B. (1997). The industrial challenge—Custom oligonucleotide synthesis. IBC Conf. Large Scale Oligonucleotide Synth., San Diego, CA, 1997. 

and Srivatsa, G. S. (1999). Analysis of internal (n — 1)-deletion sequences in synthetic oligonucleotides by hybridization to an immobilized probe array. Nucleic Acids Res. 27, 388-395. 

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