ArticleJournal of the American Chemical Society2018
An Adaptable Platform for Directed Evolution in Human Cells.
Article in Journal of the American Chemical Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 77 citations in OpenAlex.
- Harnessing the central dogma: Enzyme-driven gene diversification strategies for in cellulo continuous directed evolution.Fundamental research · 2026Review
- Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Fast analysis and engineering of protein function by microbe-independent deep assembly and screening.Molecular systems biology · 2026Article
- Programmable nanobody circuits for cell selection.bioRxiv : the preprint server for biology · 2026Article
- Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.bioRxiv : the preprint server for biology · 2025Article
- Engineering glycosyltransferases into glycan binding proteins using a mammalian surface display platform.Nature communications · 2025Article
- A chimeric viral platform for directed evolution in mammalian cells.Nature communications · 2025Article
- Nickase fidelity drives EvolvR-mediated diversification in mammalian cells.Nature communications · 2025Article
- REPLACE-ing RNA through evolution.Nature chemical biology · 2025Article
- Orthogonal RNA replication enables directed evolution and Darwinian adaptation in mammalian cells.Nature chemical biology · 2025Article
- Seamless site-directed mutagenesis in complex cloned DNA sequences using the RedEx method.Nature protocols · 2024Review
- MutaT7ACS synthetic biology · 2024Article
- Combining CRISPR-Cas-mediated terminal resolution with a novel genetic workflow to achieve high-diversity adenoviral libraries.Molecular therapy. Methods & clinical development · 2024Article
- Expanding the Scope of Adenoviral Vectors by Utilizing Novel Tools for Recombination and Vector Rescue.Viruses · 2024Article
- Enhanced Directed Evolution in Mammalian Cells Yields a Hyperefficient Pyrrolysyl tRNA for Noncanonical Amino Acid Mutagenesis.Angewandte Chemie (International ed. in English) · 2024Article
- Evolution of chemistry and selection technology for DNA-encoded library.Acta pharmaceutica Sinica. B · 2024Review
- Virus-assisted directed evolution of biomolecules.Current opinion in chemical biology · 2023Review
- Viral Evolution Shaped by Host Proteostasis Networks.Annual review of virology · 2023Review
- A dual gene-specific mutator system installs all transition mutations at similar frequencies in vivo.Nucleic acids research · 2023Article
- Expanded MutaT7 toolkit efficiently and simultaneously accesses all possible transition mutations in bacteria.Nucleic acids research · 2023Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
The discovery and optimization of biomolecules that reliably function in metazoan cells is imperative for both the study of basic biology and the treatment of disease. We describe the development, characterization, and proof-of-concept application of a platform for directed evolution of diverse biomolecules of interest (BOIs) directly in human cells. The platform relies on a custom-designed adenovirus variant lacking multiple genes, including the essential DNA polymerase and protease genes, features that allow us to evolve BOIs encoded by genes as large as 7 kb while attaining the mutation rates and enforcing the selection pressure required for successful directed evolution. High mutagenesis rates are continuously attained by trans-complementation of a newly engineered, highly error-prone form of the adenoviral polymerase. Selection pressure that couples desired BOI functions to adenoviral propagation is achieved by linking the functionality of the encoded BOI to the production of adenoviral protease activity by the human cell. The dynamic range for directed evolution can be enhanced to several orders of magnitude via application of a small-molecule adenoviral protease inhibitor to modulate selection pressure during directed evolution experiments. This platform makes it possible, in principle, to evolve any biomolecule activity that can be coupled to adenoviral protease expression or activation by simply serially passaging adenoviral populations carrying the BOI. As proof-of-concept, we use the platform to evolve, directly in the human cell environment, several transcription factor variants that maintain high levels of function while gaining resistance to a small-molecule inhibitor. We anticipate that this platform will substantially expand the repertoire of biomolecules that can be reliably and robustly engineered for both research and therapeutic applications in metazoan systems.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.