Large-scale de novo DNA synthesis: technologies and applications

By Sriram Kosuri, George M. Church. 2014

823 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

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Citations in the corpus

Accelerating Protein Design Using Autoregressive Generative Models (2019, background): “High-throughput techniques have opened up opportunities to phenotype thousands of variants in a single experiment (Kosuri & Church, 2014; Fowler & Fields, 2014), but the sampled diversity of sequences pales in comparison to that found in nature.”
A DNA-Based Archival Storage System (2016, background): “Moreover, modern array synthesis techniques [15] can synthesize complex pools of nearly 10 5 different oligonucleotides in parallel.”
Engineering Cellular Metabolism (2008, background): “Large DNA construction is one area that has greatly expanded over the past 605 several years (Kosuri and Church, 2014).”
Cognizance of Molecular Methods for the Generation of Mutagenic Phage Display Antibody Libraries for Affinity Maturation (2019, methodology): “The common advantage for all the technologies is array miniaturization; therefore, only a small amount of reagents is needed for an array [238].”
Random access in large-scale DNA data storage (2018, background): “Being able to selectively access only part of the written information (e.g., retrieving only one image from a collection) is therefore necessary to make DNA data storage viable, but so far accessing part of stored information has only been demonstrated on a small scale 8–10 .”
Genetic circuit design automation (2016, methodology): “DNA synthesis ( 91 ) and assembly were used to build each sequence; sequences contained up to 10 regulators and 55 parts.”
Protein engineering by highly parallel screening of computationally designed variants (2016, positive): “Custommicroarrays have previously been used for transcription factor specificity determination (14) and, more recently, in the screening of natural human peptide binders (15, 16).”
Recent advances in de novo protein design: Principles, methods, and applications (2021, background): “Recent developments in large-scale DNA synthesis (63) now enable high-throughput stability screening of de novo – designed small proteins (64).”