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Large-scale de novo DNA synthesis: technologies and applications

Abstract

For over 60 years, the synthetic production of new DNA sequences has helped researchers understand and engineer biology. Here we summarize methods and caveats for the de novo synthesis of DNA, with particular emphasis on recent technologies that allow for large-scale and low-cost production. In addition, we discuss emerging applications enabled by large-scale de novo DNA constructs, as well as the challenges and opportunities that lie ahead.

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Figure 1: Lengths and costs of different oligo and gene synthesis technologies.
Figure 2: Phosphoramidite chemistry.
Figure 3: Different strategies for dealing with microarray oligo complexities.
Figure 4: Comparison of reported error rates from error-correction techniques.

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Correspondence to Sriram Kosuri.

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S.K. and G.M.C. own stock in and are on the Scientific Advisory Board of Gen9, a company that sells synthetic genes. G.M.C. is on the Board of Directors of Sigma-Aldrich and the Scientific Advisory Board of Cambrian Genomics, both companies that sell synthetic genes or oligos.

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Kosuri, S., Church, G. Large-scale de novo DNA synthesis: technologies and applications. Nat Methods 11, 499–507 (2014). https://doi.org/10.1038/nmeth.2918

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