Oligonucleotide large scale

Synthetic organic polymers, which are used as polymeric supports for chromatography, as catalysts, as solid-phase supports for peptide and oligonucleotide synthesis, and for diagnosis, are based mainly on polystyrene, polystyrene-divinylbenzene, polyacrylamide, polymethacrylates, and polyvinyl alcohols. A conventional suspension of polymerization is usually used to produce these organic polymeric supports, especially in large-scale industrial production. 

Nucleotides and nucleic acids are critical tools in the areas of gene expression, therapeutics, and diagnostics. However, there are certain challenges associated with their large-scale purification and subsequent characterization. While solid-state oligonucleotide synthesis is relatively simple and can be totally automated, intra- and intermolecular associations may occur involving shorter sequences that may hybridize with the desired full length... 

Southern EM (1996) DNA chips analyzing sequence by hybridization to oligonucleotides on a large scale. Trends Genet 12 110-115... 

Lukavsky, P. J., and Puglisi, J. D. (2004). Large-scale preparation and purification of polyacrylamide-free RNA oligonucleotides. RNA 10, 889-893. 

State-of-the-art large-scale technologies for purification of therapeutic antisense oligonucleotides... 

Deshmukh, R. R., and Sanghvi, Y. S. (1997). Recent trends in large-scale purification of antisense oligonucleotides. IBC Con/. Large Scale oligonucleotide Synth., San Diego, CA, 1997. 

B. Large-Scale Production of Therapeutic Antisense Oligonucleotides... 

The next section discusses application of large-scale separation techniques to the purification of synthetic oligonucleotides. 

The final aqueous detritylation is a complicated step that requires careful process optimization, such as control of pH, oligo and salt concentrations etc. 49 After detritylation, the oligonucleotide is precipitated quantitatively from the acidic DMT cation containing solution under optimized conditions. This step can be labor intensive at the large scale, and may be inconvenient for the high-throughput small-scale synthesis. One way to circumvent the problem is to use on column detritylation, where the RP and detritylation steps are combined in one chromatographic operation. Since the acid can leach the silica based columns, this is more useful on polymeric supports. 

Johansson, H. J., and Svensson, M. A. (1995). A novel method for large-scale purification of oligonucleotides. Nucleic-acid Based Thera., San Diego, CA., 1995. 

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