Antisense oligonucleotides manufacture

Antisense oligonucleotides manufactured by direct chemical synthesis Yes No No... 

In contrast to the biopharmaceuticals discussed thus far (recombinant proteins and gene therapy products), antisense oligonucleotides are manufactured by direct chemical synthesis. Organic synthetic pathways have been developed, optimized and commercialized for some time, as oligonucleotides are widely used reagents in molecular biology. They are required as primers, probes and for the purposes of site-directed mutagenesis. 

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... 

Cole, D. L. (1999). Keynote address—GMP manufacturing of antisense oligonucleotides at Isis Pharmaceuticals for clinical trials and the marketplace Yesterday, today and tomorrow. IBC Conf. Oligonucleotide Pept. Manuf. Strategies, San Diego, CA, 1999. 

Many types of chemically modified antisense ONs have been manufactured with the changes in the overall electronic charge as well as the incorporation of nonphosphate oligonucleotide backbones. They are commonly grouped into three generations based on the type of modifications (Figure 7.5-4). 

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