Abstract

For making short DNA strands, the phosphoramidite chemistry invented and commercialized in the 1980s is hard to beat. But the method peters out after about 100 nucleotides. Applications such as synthetic biology and data storage will require longer strands than that. “If all the world needed was 20-mers or 30-mers, phosphoramidite chemistry really excels at those,” says J. William Efcavitch, who was involved in the commercialization of phosphoramidite-based DNA synthesis. “But we’re looking for longer oligonucleotides or modified oligonucleotides that are difficult, if not impossible, for the phosphoramidite chemistry.” That “we” refers to Molecular Assemblies, a San Diego-based company that hopes to use enzymes to circumvent the problems of phosphoramidite-based DNA synthesis. Efcavitch cofounded the firm in 2013 and serves as its chief scientific officer. Molecular Assemblies is not alone in wanting to make long pieces of DNA. For example, the start-up Twist Bioscience stitches together pieces made by silicon-based

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