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“Zone in with Zon”—30 Years of Automated Amidite DNA Oligo Synthesis

Dr. Gerald Zon’s latest “Zone in with Zon” blog post, August 12, 2013, hails the introduction of automated synthesis of DNA oligonucleotides (oligos) in 1983 by Applied Biosystems (ABI) as “the most enabling biotechnology yet.” Dr. Zon briefly outlines the history of this technology, beginning with the development of the phosphoramidite (amidite) methodology for oligo synthesis by Professor Marvin H. Caruthers’s research group at the University of Colorado-Boulder. This group included Serge Beaucage, Mark Matteucci, Bill Efcavitch, Curt Becker, and Lincoln McBride. The latter three joined ABI to commercialize automated oligo synthesis. Beaucage joined Beckman, which introduced its amidite-based DNA oligo synthesizer shortly after ABI. Matteuci joined Genentech to work on oligo synthesis. Dr. Zon described his role, first as a test site for ABI’s first amidite-based oligo synthesizer while he was at FDA/NIH, and later, after joining ABI in 1986 to help commercialize new applications. At ABI, Dr. Zon focused on the development of modified oligos as potential antisense inhibitors of mRNA function. In 1992, Lynx Therapeutics was spun out of ABI in order to focus on antisense therapeutics. Today, Dr. Zon reports that this field is led by Isis Pharmaceuticals and that company has recently announced FDA approval of an antisense drug to treat familial hypercholesterolemia. The Isis CEO described the drug as “the first systemic antisense drug to reach the market.” Dr. Zon went on to describe the “stunning scalability” of automated oligo synthesis, noting that the production scale of the first automated oligo synthesizer was 1 micromolar and today is approximately 750 millimolar. In addition, there are now manufacturing methods for producing small batch sizes for many thousands of different oligos. Dr. Zon closed by listing many science and technology applications that have been enabled by the availability of synthetic oligos. These include nucleic acid array-based technologies, and myriad sequencing-based technologies. Dr. Zon is an eminent nucleic acid chemist and Director of Business Development at TriLink BioTechnologies in San Diego, California. [Zon blog post]