TALENs: a widely applicable technology for targeted genome editing
J. Keith Joung,Jeffry D. Sander +1 more
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TLDR
The newly-developed transcription activator-like effector nucleases (TALENs) comprise a nonspecific DNA-cleaving nuclease fused to a DNA-binding domain that can be easily engineered so that TALens can target essentially any sequence.Abstract:
Engineered nucleases enable the targeted alteration of nearly any gene in a wide range of cell types and organisms. The newly-developed transcription activator-like effector nucleases (TALENs) comprise a nonspecific DNA-cleaving nuclease fused to a DNA-binding domain that can be easily engineered so that TALENs can target essentially any sequence. The capability to quickly and efficiently alter genes using TALENs promises to have profound impacts on biological research and to yield potential therapeutic strategies for genetic diseases.read more
Citations
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Journal ArticleDOI
Heritable and Precise Zebrafish Genome Editing Using a CRISPR-Cas System
Woong Y. Hwang,Yanfang Fu,Deepak Reyon,Morgan L. Maeder,Prakriti Kaini,Jeffry D. Sander,J. Keith Joung,Randall T. Peterson,Randall T. Peterson,Jing-Ruey J. Yeh +9 more
TL;DR: It is demonstrated that RGN-induced mutations are heritable, with efficiencies of germline transmission reaching as high as 100% and the utility of the CRISPR-Cas system in the zebrafish expands beyond somatic indel formation to heritable and precise genome modifications.
Journal ArticleDOI
Delivery technologies for genome editing
TL;DR: The principles of biomacromolecule delivery and gene editing are discussed, recent advances and challenges in non-viral and viral delivery methods are examined, and the status of related clinical trials are highlighted.
Patent
Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications
TL;DR: In this article, the authors provide delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences, including delivery systems and tissues or organ which are targeted as sites for delivery.
Journal ArticleDOI
Plant-Pathogen Effectors: Cellular Probes Interfering with Plant Defenses in Spatial and Temporal Manners.
TL;DR: This review covers recent advances in the field of effector biology, focusing on conserved cellular processes targeted by effectors from diverse pathogens.
Journal ArticleDOI
Locus-specific editing of histone modifications at endogenous enhancers using programmable TALE-LSD1 fusions
Eric M. Mendenhall,Kaylyn E. Williamson,Deepak Reyon,James Zou,Oren Ram,J. Keith Joung,Bradley E. Bernstein +6 more
TL;DR: It is found that inactivation of enhancer chromatin by TAL effector repeat domains fused to the LSD1 histone demethylase frequently causes downregulation of proximal genes, revealing enhancer target genes.
References
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Journal ArticleDOI
Breaking the Code of DNA Binding Specificity of TAL-Type III Effectors
Jens Boch,Heidi Scholze,Sebastian Schornack,Angelika Landgraf,Simone Hahn,Sabine Kay,Thomas Lahaye,Anja Nickstadt,Ulla Bonas +8 more
TL;DR: The functionality of a distinct type of DNA binding domain is described and allows the design ofDNA binding domains for biotechnology.
Journal ArticleDOI
Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting
Tomas Cermak,Erin L. Doyle,Michelle Christian,Li-Li Wang,Yong Zhang,Clarice Schmidt,Joshua A. Baller,Nikunj V. Somia,Adam J. Bogdanove,Daniel F. Voytas +9 more
TL;DR: A method and reagents for efficiently assembling TALEN constructs with custom repeat arrays are presented and design guidelines based on naturally occurring TAL effectors and their binding sites are described.
Journal ArticleDOI
A TALE nuclease architecture for efficient genome editing
Jeffrey C. Miller,Siyuan Tan,Guijuan Qiao,Kyle A. Barlow,Jianbin Wang,Danny F Xia,Xiangdong Meng,David Paschon,Elo Leung,Sarah J. Hinkley,Gladys P Dulay,Kevin Hua,Irina Ankoudinova,Gregory J. Cost,Fyodor D. Urnov,H. Steve Zhang,Michael C. Holmes,Lei Zhang,Philip D. Gregory,Edward J. Rebar +19 more
TL;DR: This study identifies TALE truncation variants that efficiently cleave DNA when linked to the catalytic domain of FokI and uses them to generate discrete edits or small deletions within endogenous human NTF3 and CCR5 genes at efficiencies of up to 25%.
Journal ArticleDOI
Genome editing with engineered zinc finger nucleases
TL;DR: A broad range of outcomes has resulted from the application of the same core technology: targeted genome cleavage by engineered, sequence-specific zinc finger nucleases followed by gene modification during subsequent repair.
Journal ArticleDOI
A Simple Cipher Governs DNA Recognition by TAL Effectors
TL;DR: It is shown that a repeat-variable pair of residues specifies the nucleotides in the target site, one pair to one nucleotide, with no apparent context dependence, which represents a previously unknown mechanism for protein-DNA recognition that explains TAL effector specificity, enables target site prediction, and opens prospects for use of TAL effects in research and biotechnology.
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