ArticleNature methods2016
Directed evolution using dCas9-targeted somatic hypermutation in mammalian cells.
Article in Nature methods, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 294 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
294 citing papers in PubMed, 472 citations in OpenAlex.
- Translating base editors: a decade of progress from the bench to the clinic.Nature reviews. Drug discovery · 2026Review
- Base editing for precision therapeutics.Cell genomics · 2026Review
- Harnessing the central dogma: Enzyme-driven gene diversification strategies for in cellulo continuous directed evolution.Fundamental research · 2026Review
- A dual A-to-Y and G-to-Y base editor and a four-base concurrent hypermutator in mammalian cells.Nature communications · 2026Article
- Exploring the Evolutionary Landscape with Targeted In Vivo Hypermutations.Biomedicines · 2026Review
- High-diversity base mutagenesis via simultaneous adenine, cytosine and guanine editing.Nature communications · 2026Article
- Incorporating AI-optimized zinc finger proteins enhances the efficiencies and targeting ranges of miniature base editors.Nature communications · 2026Article
- Scaled Multidimensional Assays of Variant Effect Identify Sequence-Function Relationships in Hypertrophic Cardiomyopathy.Circulation · 2026Article
- A Comprehensive Review on CRISPR-Based Screening and Its Applications.Molecular biotechnology · 2026Review
- Comprehensive resistance profiling of chronic myeloid leukaemia associated ABL1 variants against five tyrosine kinase inhibitors using prime editing.Nature biomedical engineering · 2026Article
- Ultramutagenesis through combined Msh2 depletion and proofreading-deficient DNA polymerase ε expression enhances small molecule target identification in forward genetic screens.bioRxiv : the preprint server for biology · 2026Article
- 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
- Base Editors for Engineering Industrial Microorganisms: Types, Applications, and Future Perspectives.Biotechnology journal · 2026Review
- The evolution of display technologies for antibody drug discovery.Trends in biotechnology · 2026Review
- DUSP11 is an RNA triphosphatase that limits PspCas13b activity by destabilizing gRNA abundance in mammalian cells.Nucleic acids research · 2026Article
- Comprehensive CRISPR/Cas9-based mutagenesis identifies single-amino acid substitutions that abrogate SPEN function in X inactivation.Nature communications · 2026Article
- CRISPR/Cas Genome Editing and Its Applications in Cereal Crop Improvement.Plant-environment interactions (Hoboken, N.J.) · 2026Review
- Precision A3G base editors for disease modeling and correction.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Therapeutic base editing alleviates restrictive cardiomyopathy.Cell reports. Medicine · 2026Article
- Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine.Nature reviews. Cardiology · 2026Review
234 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Engineering and study of protein function by directed evolution has been limited by the technical requirement to use global mutagenesis or introduce DNA libraries. Here, we develop CRISPR-X, a strategy to repurpose the somatic hypermutation machinery for protein engineering in situ. Using catalytically inactive dCas9 to recruit variants of cytidine deaminase (AID) with MS2-modified sgRNAs, we can specifically mutagenize endogenous targets with limited off-target damage. This generates diverse libraries of localized point mutations and can target multiple genomic locations simultaneously. We mutagenize GFP and select for spectrum-shifted variants, including EGFP. Additionally, we mutate the target of the cancer therapeutic bortezomib, PSMB5, and identify known and novel mutations that confer bortezomib resistance. Finally, using a hyperactive AID variant, we mutagenize loci both upstream and downstream of transcriptional start sites. These experiments illustrate a powerful approach to create complex libraries of genetic variants in native context, which is broadly applicable to investigate and improve protein function.
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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.