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Published June 2007 | Published
Journal Article Open

Synthetic Gene Circuits: Design with Directed Evolution

Abstract

Synthetic circuits offer great promise for generating insights into nature's underlying design principles or forward engineering novel biotechnology applications. However, construction of these circuits is not straightforward. Synthetic circuits generally consist of components optimized to function in their natural context, not in the context of the synthetic circuit. Combining mathematical modeling with directed evolution offers one promising means for addressing this problem. Modeling identifies mutational targets and limits the evolutionary search space for directed evolution, which alters circuit performance without the need for detailed biophysical information. This review examines strategies for integrating modeling and directed evolution and discusses the utility and limitations of available methods.

Additional Information

"Reprinted, with permission, from the Annual Review of Biophysics and Biomolecular Structure, Volume 36 copyright 2007 by Annual Reviews, www.annualreviews.org" First published online as a Review in Advance on December 13, 2006 ELH is supported by the Caltech Center for Biological Circuit Design. FHA acknowledges support from the NSF and NIH. We thank R. Weiss and L. You for comments on the manuscript.

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August 22, 2023
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October 16, 2023