ArticleNucleic acids research2020
A heterodimer of evolved designer-recombinases precisely excises a human genomic DNA locus.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Programmable enzymes for targeted gene insertion.Nature reviews. Genetics · 2026Review
- From Gene Knockouts to Genome Remodeling: Large DNA Fragment Deletion Technologies in Plants.Plants (Basel, Switzerland) · 2026Review
- Site-specific DNA insertion into the human genome with engineered recombinases.Nature biotechnology · 2025Article
- Activation of recombinases at specific DNA loci by zinc-finger domain insertions.Nature biotechnology · 2024Article
- Thermostable bacterial L-asparaginase for polyacrylamide inhibition and in silico mutational analysis.International microbiology : the official journal of the Spanish Society for Microbiology · 2024Article
- Engineering spacer specificity of the Cre/loxP system.Nucleic acids research · 2024Article
- Article
- Bridge RNAs direct modular and programmable recombination of target and donor DNA.bioRxiv : the preprint server for biology · 2024Article
- Recent Advances in Double-Strand Break-Free Kilobase-Scale Genome Editing Technologies.Biochemistry · 2023Review
- Quantification of evolved DNA-editing enzymes at scale with DEQSeq.Genome biology · 2023Article
- Precise excision of HTLV-1 provirus with a designer-recombinase.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Discovery and characterization of novel Cre-type tyrosine site-specific recombinases for advanced genome engineering.Nucleic acids research · 2023Article
- Thermostability enhancement and insight of L-asparaginase from Mycobacterium sp. via consensus-guided engineering.Applied microbiology and biotechnology · 2023Article
- Prediction of designer-recombinases for DNA editing with generative deep learning.Nature communications · 2022Article
- Gene editing and its applications in biomedicine.Science China. Life sciences · 2022Review
- Pairing of single mutations yields obligate Cre-type site-specific recombinases.Nucleic acids research · 2022Article
- Correction of a Factor VIII genomic inversion with designer-recombinases.Nature communications · 2022Article
- Conformational dynamics promotes disordered regions from function-dispensable to essential in evolved site-specific DNA recombinases.Computational and structural biotechnology journal · 2022Article
- Genome targeting by hybrid Flp-TAL recombinases.Scientific reports · 2020Article
- Gene drive and resilience through renewal with next generationProceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
7 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Site-specific recombinases (SSRs) such as the Cre/loxP system are useful genome engineering tools that can be repurposed by altering their DNA-binding specificity. However, SSRs that delete a natural sequence from the human genome have not been reported thus far. Here, we describe the generation of an SSR system that precisely excises a 1.4 kb fragment from the human genome. Through a streamlined process of substrate-linked directed evolution we generated two separate recombinases that, when expressed together, act as a heterodimer to delete a human genomic sequence from chromosome 7. Our data indicates that designer-recombinases can be generated in a manageable timeframe for precision genome editing. A large-scale bioinformatics analysis suggests that around 13% of all human protein-coding genes could be targetable by dual designer-recombinase induced genomic deletion (dDRiGD). We propose that heterospecific designer-recombinases, which work independently of the host DNA repair machinery, represent an efficient and safe alternative to nuclease-based genome editing technologies.
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