TAL Effectors: Customizable Proteins for DNA Targeting

Bogdanove, Adam J.; Voytas, Daniel F.

doi:10.1126/science.1204094

Cited by 888 publications

(639 citation statements)

References 36 publications

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“…This modified TALEN platform was used to efficiently induce mutations in Xenopus and zebrafish. Although previous studies have shown that TALEN has high specificity (Bogdanove and Voytas 2011;Huang et al 2011;Hwang et al 2013;Lei et al 2012;Liu et al 2013Liu et al , 2014Sander et al 2011), offtarget problems remained underestimated. On the one hand, while HD, NI, and NG RVDs of TALENs could specifically correspond with C, A, and T, only NN can identify both G and A, indicating that the more G in the target sequence, the more NN is required in the corresponding synthetic TALEN artificial nucleases, but this increases the opportunity for nonspecific knockouts.…”

Section: Discussionmentioning

confidence: 99%

“…TALENs are artificial nucleases that consist of DNA binding domains of transcription activator-like (TAL) effector and catalytic Fok I domains (Bogdanove and Voytas 2011). After assemblage, the TAL repeating unit combines with specific DNA sequences, and each TAL identifies a DNA base.…”

Section: Introductionmentioning

confidence: 99%

“…Targeted genome modification technology can be mediated by zinc finger nucleases (ZFNs) (Doyon et al 2008;Kim et al 1996;Osiak et al 2011), transcription activator-like effector nucleases (TALENs) (Bogdanove and Voytas 2011;Huang et al 2011;Sander et al 2011), and type II prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR) (Cong et al 2013;Hwang et al 2013). TALENs are artificial nucleases that consist of DNA binding domains of transcription activator-like (TAL) effector and catalytic Fok I domains (Bogdanove and Voytas 2011).…”

Section: Introductionmentioning

confidence: 99%

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Efficient Knockout of Transplanted Green Fluorescent Protein Gene in Medaka Using TALENs

et al. 2014

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Transcription activator-like effector nucleases (TALENs) are used for gene knockout and genome-editing studies in zebrafish, and these techniques have the potential to be applied to other fish species. Here, we show that TALENs can directly knock out a green fluorescent protein (GFP) transgene in medaka by affecting translation and synthesis of the GFP. We constructed a transgenic plasmid (pGFP-RFP) carrying the GFP and red fluorescent protein (RFP) genes, and used a modified TALEN method to assemble a pair of TALENs for the core chromophore Y66 region of GFP. Embryo toxicity of TALEN messenger RNA (mRNA) was far lower than the linearized plasmid; meanwhile, 76.3 % embryos, green fluorescence of embryos decreased significantly after co-injection of TALEN mRNA and the linearized plasmid, but red fluorescence showed no significant change. Real-time quantitative polymerase chain reaction and sequencing results showed that nearly 100 % mutated GFP position was disrupted at the Y66 region of GFP in the coinjected medaka embryos, caused by TALENs. This led to random insertion-deletion of nucleotides, which affected the translation of GFP and disrupted GFP synthesis. This provides new experimental evidence for designing TALEN sites in genes for which only key functional domains are known. Our results show that a modified TALEN method can efficiently and specifically mediate a transgene knockout in medaka. This report may promote the application of TALENs in gene-editing studies of fish species other than zebrafish.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficient Knockout of Transplanted Green Fluorescent Protein Gene in Medaka Using TALENs

et al. 2014

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“…In the first, the precise nature of the catalytic enzymes is disregarded and the goal is merely to deliver epigenetic marks that are either permissive or refractory for gene expression. Platforms such as zinc finger nucleases 44 and transcription activator‐like effector nucleases (TALENs) 45 were the first reagents to employ these technologies enabling delivery to precise genomic locations. Their use has been eclipsed by the clustered, regularly interspaced, short palindromic repeats (CRISPR)‐Cas9 system 46.…”

Section: Dna Methylation and Demethylationmentioning

confidence: 99%

CRISPR-based reagents to study the influence of the epigenome on gene expression

Lavender

Kelly

Hendy

et al. 2018

Clinical and Experimental Immunology

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SummaryThe use of epigenome editing is set to expand our knowledge of how epigenetic landscapes facilitate gene expression capacity within a given cell. As epigenetic landscape profiling in health and disease becomes more commonplace, so does the requirement to assess the functional impact that particular regulatory domains and DNA methylation profiles have upon gene expression capacity. That functional assessment is particularly pertinent when analysing epigenomes in disease states where the reversible nature of histone and DNA modification might yield plausible therapeutic targets. In this review we discuss first the nature of the epigenetic landscape, secondly the types of factors that deposit and erase the various modifications, consider how modifications transduce their signals, and lastly address current tools for experimental epigenome editing with particular emphasis on the immune system.

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“…Replacements can be achieved by providing donor DNA at the time at which the ZFN is induced; in the absence of a repair template, the break is joined in an error-prone manner to yield a gene knockout. Building on the success of ZFNs, a secondgeneration class of gene-targeting enzymes has emerged that uses DNA-binding modules based on transcription-activatorlike (TAL) effectors of plant bacterial pathogens (Bogdanove and Voytas 2011). Although the TAL-effector nucleases, or TALENs, have technical advantage over the original ZFNs, ZFNs provided the intellectual framework for their development.…”

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confidence: 99%

The 2012 Novitski Prize

Jinks-Robertson¹

2012

Genetics

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T HE Edward Novitski Prize is named in honor of Drosophila geneticist Edward Novitski (1928Novitski ( -2006 and is awarded to recognize the "creativity and intellectual ingenuity" that goes into solving a difficult genetic problem. This year's Novitski Prize recognizes Dana Carroll for his insight into the potential use of zinc-finger nucleases (ZFNs) for genome modification and for his work demonstrating the broad applicability of this technique. ZFNs can be used to create targeted mutations in a broad range of organisms, allowing efficient "reverse" genetics in those organisms whose genomes are otherwise very difficult to manipulate. The basic technology can be used to correct defective genes as well, opening the door for the potential use of ZFNs in gene therapy.Dana's career path has not been that of a typical Novitski Prize winner. He was formally trained as a chemist rather than as a geneticist. He majored in chemistry as an undergraduate at Swarthmore College and subsequently received a Ph.D. in biophysical chemistry at the University of California at Berkeley, where he worked with Ignacio Tinoco, Jr., on nucleic acid structure. Dana's first postdoctoral experience was with John Paul at the Beatson Institute for Cancer Research in Scotland, where he was introduced to the more the biological side of science. He then moved to the Carnegie Institution of Washington in Baltimore for further postdoctoral work in the lab of Don Brown, and it was there that Dana initiated studies on 5S ribosomal DNA in Xenopus laevis. Although these studies continued when Dana set up his own lab at the University of Utah in 1975, his focus shifted to the fate of DNA injected into Xenopus oocytes in the mid-1980s. He subsequently made important contributions to the recombination field, elucidating basic mechanisms of homogolous and nonhomologous/illegitimate recombination using the Xenopus system (Carroll 1998). Minus one sabbatical, Dana has remained at Utah his entire career, which has included a 24-year stint as chair of the Department of Biochemistry.With the development of recombinant DNA technologies and methods to introduce DNA into cells in the 1970s, it became feasible to modify the genetic material of model microorganisms. These developments were, in large part, responsible for the rapid emergence of Saccharomyces cerevisiae as the premier eukaryotic genetic system. What set yeast apart from other experimental systems was the robust nature of homologous relative to nonhomologous recombination, which allowed efficient targeting of plasmid DNA to the cognate genome location. This is in stark contrast to most other eukaryotes, where nonhomologous recombination events predominate over homology-based events, and exogenous DNA integrates randomly and unpredictably. It was subsequently discovered that linearizing the exogenous DNA dramatically increased the gene-targeting efficiency in yeast and hence that double-strand breaks (DSBs) were efficient initiators of recombination (Orr-Weaver et al. 1981). Finally, the use of mega-...

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TAL Effectors: Customizable Proteins for DNA Targeting

Cited by 888 publications

References 36 publications

Efficient Knockout of Transplanted Green Fluorescent Protein Gene in Medaka Using TALENs

Efficient Knockout of Transplanted Green Fluorescent Protein Gene in Medaka Using TALENs

CRISPR-based reagents to study the influence of the epigenome on gene expression

The 2012 Novitski Prize

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