ABSTRACT
The ability to inhibit gene expression by synthetic oligonucleotides has attracted intense interest to antisense DNA as a novel class of chemotherapeutic agents (Agrawal, 1996; Zamecnik, 1991). As the number of oligonucleotides entering clinical trials increases, so does the demand for increasing amounts of highly pure synthetic oligonucleotides. In the recent past, one apparent obstacle to the successful application of oligonucleotides for therapeutic use had been the inability to produce them at large scale (Seliger, 1993; Sinha, 1993). Another perceived hurdle to the commercialization of synthetic oligonucleotides was the inability to produce them at sufficient purity under current Good Manufacturing Practices (cGMPs). As recently as 1991, it was speculated that 100 grams of a 21-mer phosphorothioate (PS) would cost $1.2 million (Zon and Geiser, 1991).
