ArticlePloS one2013
The design and in vivo evaluation of engineered I-OnuI-based enzymes for HEG gene drive.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Germline Cas9 promoters with improved performance for homing gene drive.Nature communications · 2024Article
- A CRISPR endonuclease gene drive reveals distinct mechanisms of inheritance bias.Nature communications · 2022Article
- The Challenges in Developing Efficient and Robust Synthetic Homing Endonuclease Gene Drives.Frontiers in bioengineering and biotechnology · 2022Review
- Driving down malaria transmission with engineered gene drives.Frontiers in genetics · 2022Review
- Adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post-market environmental monitoring of genetically modified insects containing engineered gene drives.EFSA journal. European Food Safety Authority · 2020Article
- Modifying a covarying protein-DNA interaction changes substrate preference of a site-specific endonuclease.Nucleic acids research · 2019Article
- Cleave and Rescue, a novel selfish genetic element and general strategy for gene drive.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Active site residue identity regulates cleavage preference of LAGLIDADG homing endonucleases.Nucleic acids research · 2018Article
- Controlling vector-borne diseases by releasing modified mosquitoes.Nature reviews. Microbiology · 2018Review
- Engineering altered protein-DNA recognition specificity.Nucleic acids research · 2018Review
- Gene Drive: Evolved and Synthetic.ACS chemical biology · 2018Review
- Crystallographic analyses illustrate significant plasticity and efficient recoding of meganuclease target specificity.Nucleic acids research · 2017Article
- Tuning DNA binding affinity and cleavage specificity of an engineered gene-targeting nuclease via surface display, flow cytometry and cellular analyses.Protein engineering, design & selection : PEDS · 2017Article
- Novel CRISPR/Cas9 gene drive constructs reveal insights into mechanisms of resistance allele formation and drive efficiency in genetically diverse populations.PLoS genetics · 2017Article
- Requirements for Driving Antipathogen Effector Genes into Populations of Disease Vectors by Homing.Genetics · 2017Article
- Programmable Genome Editing Tools and their Regulation for Efficient Genome Engineering.Computational and structural biotechnology journal · 2017Review
- Indirect DNA Sequence Recognition and Its Impact on Nuclease Cleavage Activity.Structure (London, England : 1993) · 2016Article
- Cheating evolution: engineering gene drives to manipulate the fate of wild populations.Nature reviews. Genetics · 2016Review
- The Structural Basis of Asymmetry in DNA Binding and Cleavage as Exhibited by the I-SmaMI LAGLIDADG Meganuclease.Journal of molecular biology · 2016Article
- Massively parallel determination and modeling of endonuclease substrate specificity.Nucleic acids research · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The homing endonuclease gene (HEG) drive system, a promising genetic approach for controlling arthropod populations, utilises engineered nucleases to spread deleterious mutations that inactivate individual genes throughout a target population. Previous work with a naturally occurring LAGLIDADG homing endonuclease (I-SceI) demonstrated its feasibility in both Drosophila and Anopheles. Here we report on the next stage of this strategy: the redesign of HEGs with customized specificity in order to drive HEG-induced 'homing' in vivo via break-induced homologous recombination. Variants targeting a sequence within the Anopheles AGAP004734 gene were created from the recently characterized I-OnuI endonuclease, and tested for cleavage activity and frequency of homing using a model Drosophila HEG drive system. We observed cleavage and homing at an integrated reporter for all endonuclease variants tested, demonstrating for the first time that engineered HEGs can cleave their target site in insect germline cells, promoting targeted mutagenesis and homing. However, in comparison to our previously reported work with I-SceI, the engineered I-OnuI variants mediated homing with a reduced frequency, suggesting that site-specific cleavage activity is insufficient by itself to ensure efficient homing. Taken together, our experiments take a further step towards the development of a viable HEG-based population control strategy for insects.
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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.