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Open AccessJournal ArticleDOI

TALENs: a widely applicable technology for targeted genome editing

J. Keith Joung, +1 more
- 01 Jan 2013 - 
- Vol. 14, Iss: 1, pp 49-55
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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.

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Citations
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MLL leukemia induction by genome editing of human CD34+ hematopoietic cells

TL;DR: Genome editing to create endogenous MLL oncogenes in primary human HSPCs faithfully models acute MLL-rearranged leukemia and provides an experimental platform for prospective studies of leukemia initiation and stem cell biology in a genetic subtype of poor prognosis leukemia.
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The epigenome: the next substrate for engineering

TL;DR: The design and state of epigenome editing tools are reviewed, highlighting the unique regulatory properties afforded by these systems.
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CRISPR‐Cas targeted plasmid integration into mammalian cells via non‐homologous end joining

TL;DR: It is shown that a site specific double strand break (DSB) generated both in the genome and the donor plasmid using the CRISPR‐Cas9 system can be efficiently used to target ∼5 kb plasmids into mammalian genomes via nonhomologous end joining (NHEJ).
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CRISPR-Cas9 gene editing: Delivery aspects and therapeutic potential

TL;DR: The transformation of the CRISPR-Cas gene editing systems into a therapeutic modality will be discussed and the currently most realistic in vivo applications will be highlighted.
References
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Journal ArticleDOI

Breaking the Code of DNA Binding Specificity of TAL-Type III Effectors

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

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

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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