Targeting DNA Double-Strand Breaks with TAL Effector Nucleases

Christian, Michelle; Čermák, Tomáš; Doyle, Erin L.; Schmidt, Claude H.; Zhang, Feng; Hummel, Aaron W.; Bogdanove, Adam J.; Voytas, Daniel F.

doi:10.1534/genetics.110.120717

Cited by 1,711 publications

(1,184 citation statements)

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“…S everal types of highly specific DNA recognition and cleavage enzymes, including homing endonucleases (HEs), zinc finger nucleases (ZFNs), and transcription activator-like (TAL) effector nucleases, are being developed for targeted gene modification, ranging from gene disruption to corrective gene therapy (1)(2)(3)(4)(5). Regardless of the identity of the protein scaffold, site-specific gene modification generally requires the creation of individually tailored site-specific endonucleases that generate double-strand breaks (DSBs) at unique chromosomal targets.…”

mentioning

confidence: 99%

Tapping natural reservoirs of homing endonucleases for targeted gene modification

Takeuchi

Lambert²,

Mak

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

110

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Homing endonucleases mobilize their own genes by generating double-strand breaks at individual target sites within potential host DNA. Because of their high specificity, these proteins are used for “genome editing” in higher eukaryotes. However, alteration of homing endonuclease specificity is quite challenging. Here we describe the identification and phylogenetic analysis of over 200 naturally occurring LAGLIDADG homing endonucleases (LHEs). Biochemical and structural characterization of endonucleases from one clade within the phylogenetic tree demonstrates strong conservation of protein structure contrasted against highly diverged DNA target sites and indicates that a significant fraction of these proteins are sufficiently stable and active to serve as engineering scaffolds. This information was exploited to create a targeting enzyme to disrupt the endogenous monoamine oxidase B gene in human cells. The ubiquitous presence and diversity of LHEs described in this study may facilitate the creation of many tailored nucleases for genome editing.

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mentioning

confidence: 99%

Tapping natural reservoirs of homing endonucleases for targeted gene modification

Takeuchi

Lambert²,

Mak

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

110

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“…However, translation of these findings to human cells was, for a long time, complicated by the fact that homologous recombination in human cells proved to be highly inefficient 35. With the recent advent of genome editing technologies such as ZFNs 36, transcription activator‐like effector nucleases 37, and CRISPR‐Cas/RNA‐guided nucleases 38, gene editing has become broadly applicable to human cells. Typically, these techniques are applied to human pluripotent stem cells, which are then used to derive defined somatic cell types required for the individual application.…”

Section: Discussionmentioning

confidence: 99%

Genome Editing in Neuroepithelial Stem Cells to Generate Human Neurons with High Adenosine-Releasing Capacity

Poppe

Doerr

Schneider

et al. 2018

Stem Cells Translational Medicine

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As a powerful regulator of cellular homeostasis and metabolism, adenosine is involved in diverse neurological processes including pain, cognition, and memory. Altered adenosine homeostasis has also been associated with several diseases such as depression, schizophrenia, or epilepsy. Based on its protective properties, adenosine has been considered as a potential therapeutic agent for various brain disorders. Since systemic application of adenosine is hampered by serious side effects such as vasodilatation and cardiac suppression, recent studies aim at improving local delivery by depots, pumps, or cell‐based applications. Here, we report on the characterization of adenosine‐releasing human embryonic stem cell‐derived neuroepithelial stem cells (long‐term self‐renewing neuroepithelial stem [lt‐NES] cells) generated by zinc finger nuclease (ZFN)‐mediated knockout of the adenosine kinase (ADK) gene. ADK‐deficient lt‐NES cells and their differentiated neuronal and astroglial progeny exhibit substantially elevated release of adenosine compared to control cells. Importantly, extensive adenosine release could be triggered by excitation of differentiated neuronal cultures, suggesting a potential activity‐dependent regulation of adenosine supply. Thus, ZFN‐modified neural stem cells might serve as a useful vehicle for the activity‐dependent local therapeutic delivery of adenosine into the central nervous system. stem cells translational medicine 2018;7:477–486

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“…DOSSIER TECHNIQUE REVUES niers sont souvent préférés aux di-résidus NK et NH en raison d'une plus forte affinité pour leur cible [12,13]. La région de liaison à l'ADN des TALE se termine par la dernière répétition (LR, last repeat) qui n'est composée que de 20 résidus, mais possède toutefois les di-résidus variables qui assurent la spécificité de liaison à un nucléotide particulier.…”

Section: Talen Et Ingénierie Génomiqueunclassified

“…Au sein des répétitions, ce sont les acides aminés 12 et 13 qui déterminent la spécificité de liaison aux nucléotides de chacun de ces domaines répétés [9][10][11] (Figure 1C Figure 3B). Ainsi, la technologie d'édition des génomes à l'aide des TALEN, en induisant un grand nombre de modifications génome par réparation de la cassure double-brin [13,18]. La dimé-risation du domaine nucléasique de FokI est nécessaire au clivage de l'ADN.…”

Section: Talen Et Ingénierie Génomiqueunclassified

“…Depuis leur première utilisation rapportée en 2010 [13], les TALEN ont été largement utilisés aussi bien in vitro dans des cellules en culture, génomiques différentes, ouvre de larges champs d'application et offre de nombreuses perspectives thérapeutiques. Les TALEN sont largement employés pour induire l'inactivation de gènes [19, 20, 22-25, 29-31, 34-39], mais aussi pour restaurer la fonction de gènes mutants [41], introduire des marqueurs de l'expression génique, tels que la GFP (green fluorescent protein) [34], ou générer des translocations chromosomiques [43].…”

Section: Champs D'application Des Talenunclassified

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L’ingénierie des génomes par les TALEN

Dupret

Angrand

2014

Med Sci (Paris)

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> La modification précise des génomes est un des enjeux majeurs des biotechnologies et de la recherche biomédicale. La découverte des TALE (transcription activator-like effector) et le développement récent des TALEN (transcription activator-like effector nuclease) artificiels offrent la possibilité d'éditer les génomes de nombreux organismes modèles de manière rapide, spécifique et efficace. Les TALEN sont des ciseaux moléculaires qui permettent d'induire différentes modifications génétiques en un site choisi du génome, et il est probable qu'ils deviennent, au cours des prochaines années, un des outils incontournables de la génétique inverse appliquée à la médecine. <

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Targeting DNA Double-Strand Breaks with TAL Effector Nucleases

Cited by 1,711 publications

References 20 publications

Tapping natural reservoirs of homing endonucleases for targeted gene modification

Tapping natural reservoirs of homing endonucleases for targeted gene modification

Genome Editing in Neuroepithelial Stem Cells to Generate Human Neurons with High Adenosine-Releasing Capacity

L’ingénierie des génomes par les TALEN

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