ArticleNucleic acids research2013
Engineering of a target site-specific recombinase by a combined evolution- and structure-guided approach.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Activation of recombinases at specific DNA loci by zinc-finger domain insertions.Nature biotechnology · 2024Article
- Engineering spacer specificity of the Cre/loxP system.Nucleic acids research · 2024Article
- Expanding the DNA editing toolbox: Novel lambda integrase variants targeting microalgal and human genome sequences.PloS one · 2024Article
- Precise excision of HTLV-1 provirus with a designer-recombinase.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- LncRNA Osilr9 coordinates promoter DNA demethylation and the intrachromosomal loop structure required for maintaining stem cell pluripotency.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
- Prediction of designer-recombinases for DNA editing with generative deep learning.Nature communications · 2022Article
- Mechanisms of Cre recombinase synaptic complex assembly and activation illuminated by Cryo-EM.Nucleic acids research · 2022Article
- 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
- Nearest-neighbor amino acids of specificity-determining residues influence the activity of engineered Cre-type recombinases.Scientific reports · 2020Article
- A heterodimer of evolved designer-recombinases precisely excises a human genomic DNA locus.Nucleic acids research · 2020Article
- Engineering altered protein-DNA recognition specificity.Nucleic acids research · 2018Review
- Crystal structure of an engineered, HIV-specific recombinase for removal of integrated proviral DNA.Nucleic acids research · 2017Article
- CRISPR Genome Engineering for Human Pluripotent Stem Cell Research.Theranostics · 2017Review
- Discovery of Nigri/nox and Panto/pox site-specific recombinase systems facilitates advanced genome engineering.Scientific reports · 2016Article
- Directed evolution of a recombinase that excises the provirus of most HIV-1 primary isolates with high specificity.Nature biotechnology · 2016Article
- Site promiscuity of coliphage HK022 integrase as a tool for gene therapy.Gene therapy · 2015Article
- Inhibition of HIV-1 Viral Infection by an Engineered CRISPR Csy4 RNA Endoribonuclease.PloS one · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Site-specific recombinases (SSRs) can perform DNA rearrangements, including deletions, inversions and translocations when their naive target sequences are placed strategically into the genome of an organism. Hence, in order to employ SSRs in heterologous hosts, their target sites have to be introduced into the genome of an organism before the enzyme can be practically employed. Engineered SSRs hold great promise for biotechnology and advanced biomedical applications, as they promise to extend the usefulness of SSRs to allow efficient and specific recombination of pre-existing, natural genomic sequences. However, the generation of enzymes with desired properties remains challenging. Here, we use substrate-linked directed evolution in combination with molecular modeling to rationally engineer an efficient and specific recombinase (sTre) that readily and specifically recombines a sequence present in the HIV-1 genome. We elucidate the role of key residues implicated in the molecular recognition mechanism and we present a rationale for sTre's enhanced specificity. Combining evolutionary and rational approaches should help in accelerating the generation of enzymes with desired properties for use in biotechnology and biomedicine.
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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.