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TALENs: a widely applicable technology for targeted genome editing
Open accessAbstract
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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“Each repeat binds to a single nucleotide, and the amino acids residues in the positions 12 and 13 of that repeat determine which nucleotide is bound [91].”
From CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool (2019) · cites this paper as [91]
In the citing paper
“The discovery that TALEs use a simple modular code for DNA recognition has provided an alternative platform for genome editing and gene disruption.”
From Newer Gene Editing Technologies toward HIV Gene Therapy (2013) · cites this paper as [66]
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Citations
Cites
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Influential
Cited by
Sorted by citations
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Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting
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“Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) are custom-designed endonucleases that enable site-specific genome editing, but their widespread application has been limited by reagent complexity and cost (1, 2).”
Targeted genome editing in human repopulating haematopoietic stem cells
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“Transcription activator–like effector (TALE) nucleases (TALENs) employ DNA-binding modules from bacterial TALEs linked to the same FokI cleavage domain (20).”
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“…genome editing methodologies such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) (Urnov et al., 2010);(Joung and Sander, 2013; Scharenberg et al., 2013) have enabled site-specific gene repair or ablation and raised the possibility of treating a broad…”
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“TALENs are easy to design but require laborious cloning steps (Joung and Sander, 2013).”
BackgroundBase editing: advances and therapeutic opportunities
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Applications of the CRISPR-Cas9 system in cancer biology
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Heritable and Precise Zebrafish Genome Editing Using a CRISPR-Cas System
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“Compared to the CRISPR/Cas system, TALENs are more costly to generate, but they have a better theoretical targeting range (at least three TALENs can be made for every single bp in random DNA sequence) [12].”
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“…including Zinc-finger Nucleases (ZFN) (Bibikova et al., 2002; Gupta et al., 2012), Transcription activator-like effector nucleases (TALEN) (Joung and Sander, 2013; Miller et al., 2011; Zu et al., 2013) and clustered regularly interspaced short palindromic repeats (CRISPR) (Hwang et al.,…”
BackgroundBestrophin 1 and retinal disease
Johnson, A. A., Guziewicz, K. E., Lee, C. J., Kalathur, R., Pulido, J. S., Marmorstein, L. Y., & Marmorstein, A. D. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.01.006 · Cited by 241
Integrated approaches in microbial degradation of plastics
Jaiswal, S., Sharma, B., & Shukla, P. (2019) · Environmental Technology & Innovation · doi:10.1016/j.eti.2019.100567 · Cited by 243
Enhancer redundancy in development and disease
Kvon, E. Z., Waymack, R., Gad, M., & Wunderlich, Z. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-020-00311-x · Cited by 247
Digital logic circuits in yeast with CRISPR-dCas9 NOR gates
Gander, M. W., Vrana, J. D., Voje, W. E., Carothers, J. M., & Klavins, E. (2017) · Nature Communications · doi:10.1038/ncomms15459 · Cited by 247
Efficient CRISPR/Cas9 Genome Editing of Phytoene desaturase in Cassava
Odipio, J., Alicai, T., Ingelbrecht, I., Nusinow, D. A., Bart, R. S., & Taylor, N. J. (2017) · Frontiers in Plant Science · doi:10.3389/fpls.2017.01780 · Cited by 247
“Subsequent repair at the target site introduces variation via error prone non-homologous end joining (NHEJ) (Sonoda et al., 2006; Curtin et al., 2012; Joung and Sander, 2013) to generate insertions and deletions (INDELs), with occasional substitution of nucleotides occurring at the repair regions.”
BackgroundTowards social acceptance of plant breeding by genome editing
Araki, M., & Ishii, T. (2015) · Trends in Plant Science · doi:10.1016/j.tplants.2015.01.010 · Cited by 247
“For example, enhanced modification specificity can be achieved via the use of more sophisticated nucleases and meticulously designed homing molecules [1-3].”
BackgroundZhen, S., Hua, L., Liu, Y.-H., Gao, L.-C., Fu, J., Wan, D.-Y., Dong, L.-H., Song, H.-F., & Gao, X. (2015) · Gene Therapy · doi:10.1038/gt.2015.2 · Cited by 215
Oceguera-Yañez, F., Kim, S., Matsumoto, T., Tan, G. W., Xiang, L., Hatani, T., Kondo, T., Ikeya, M., Yoshida, Y., Inoue, H., et al. (2015) · Methods · doi:10.1016/j.ymeth.2015.12.012 · Cited by 232
“As conventional gene targeting events are rare, recombinant proteins such as zinc finger nucleases (ZFNs) [6], TALE nucleases (TALENs) [7], and CRISPR/Cas9 [8] can be used to induce double-strand breaks (DSBs) at target sites in the genome, stimulating endogenous cellular DNA damage response and repair pathways [9].”
BackgroundA CRISPR view of developmentPreprint
Harrison, M. M., Jenkins, B., O’Connor-Giles, K. M., & Wildonger, J. (2014) · Genes & Development · doi:10.1101/gad.248252.114 · Cited by 234
Targeted mutagenesis using CRISPR/Cas system in medaka
Ansai, S., & Kinoshita, M. (2014) · Biology Open · doi:10.1242/bio.20148177 · Cited by 227
“Genome editing with artificial nucleases such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) has become a powerful tool for approaches involving reverse genetics in a wide range of organisms (Carroll, 2011; Joung and Sander, 2013).”
BackgroundSchneider, N., Sundaresan, Y., Gopalakrishnan, P., Beryozkin, A., Hanany, M., Levanon, E. Y., Banin, E., Ben‐Aroya, S., & Sharon, D. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.101029 · Cited by 231
Genetic engineering of microalgae for enhanced biorefinery capabilities
Fayyaz, M., Chew, K. W., Show, P. L., Ling, T. C., Ng, I.-S., & Chang, J.-S. (2020) · Biotechnology Advances · doi:10.1016/j.biotechadv.2020.107554 · Cited by 225
Common marmoset as a new model animal for neuroscience research and genome editing technology
Kishi, N., Sato, K., Sasaki, E., & Okano, H. (2014) · Development Growth & Differentiation · doi:10.1111/dgd.12109 · Cited by 224
“To overcome this bottleneck for generation of knock-out/knock-in marmosets, researchers are examining the potential of genome editing tools, namely engineered nucleases (Carroll 2011; Gaj et al. 2013; Joung & Sander 2013).”
BackgroundCAR T-cell therapy for B-cell lymphomas: clinical trial results of available products
Chávez, J. C., Bachmeier, C. A., & Kharfan‐Dabaja, M. A. (2019) · Therapeutic Advances in Hematology · doi:10.1177/2040620719841581 · Cited by 225
Mao, Y., Zhang, Z., Feng, Z., Wei, P., Zhang, H., Botella, J. R., & Zhu, J. (2015) · Plant Biotechnology Journal · doi:10.1111/pbi.12468 · Cited by 222
Bloom, K., Ely, A., Mussolino, C., Cathomen, T., & Arbuthnot, P. (2013) · Molecular Therapy · doi:10.1038/mt.2013.170 · Cited by 217
Plant Genome Engineering for Targeted Improvement of Crop Traits
Sedeek, K. E. M., Mahas, A., & Mahfouz, M. M. (2019) · Frontiers in Plant Science · doi:10.3389/fpls.2019.00114 · Cited by 237
Application of CRISPR/Cas9 in Crop Quality Improvement
Liu, Q., Yang, F., Zhang, J., Liu, H., Rahman, S., Islam, S., Ma, W., & She, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084206 · Cited by 239
Evolution of transcription factor binding in metazoans — mechanisms and functional implications
Villar, D., Flicek, P., & Odom, D. T. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3481 · Cited by 217
CRISPR-Cas: New Tools for Genetic Manipulations from Bacterial Immunity Systems
Jiang, W., & Marraffini, L. A. (2015) · Annual Review of Microbiology · doi:10.1146/annurev-micro-091014-104441 · Cited by 219
Arazoe, T., Miyoshi, K., Yamato, T., Ogawa, T., Ohsato, S., Arie, T., & Kuwata, S. (2015) · Biotechnology and Bioengineering · doi:10.1002/bit.25662 · Cited by 211
Chronic Granulomatous Disease: a Comprehensive Review
Yu, H.-H., Yang, Y.-H., & Chiang, B.-L. (2021) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-020-08800-x · Cited by 197
Zebrafish models in translational research: tipping the scales toward advancements in human health
Phillips, J. B., & Westerfield, M. (2014) · Disease Models & Mechanisms · doi:10.1242/dmm.015545 · Cited by 206
“Most recently, the development of genome-editing techniques, including transcription activator-like effector nucleases (TALENs) (Joung and Sander, 2013) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 (Chang et al., 2013; Hruscha et al., 2013; Hwang et al., 2013), has…”
Wahane, A. V., Waghmode, A., Kapphahn, A., Dhuri, K., Gupta, A., & Bahal, R. (2020) · Molecules · doi:10.3390/molecules25122866 · Cited by 202
Debbarma, J., Sarki, Y. N., Saikia, B., Boruah, H. P. D., Singha, D. L., & Chikkaputtaiah, C. (2019) · Molecular Biotechnology · doi:10.1007/s12033-018-0144-x · Cited by 199
Gene editing and CRISPR in the clinic: current and future perspectives
Hirakawa, M. P., Krishnakumar, R., Timlin, J. A., Carney, J. P., & Butler, K. S. (2020) · Bioscience Reports · doi:10.1042/bsr20200127 · Cited by 207
Curtin, S. J., Xiong, Y., Michno, J., Campbell, B. W., Stec, A. O., Čermák, T., Starker, C. G., Voytas, D. F., Eamens, A. L., & Stupar, R. M. (2017) · Plant Biotechnology Journal · doi:10.1111/pbi.12857 · Cited by 192
“The TALEN platform has a limitless targeting range that might be advantageous for targeting a highly specific locus (Joung and Sander, 2013).”
BackgroundDNA methylation in social insects: how epigenetics can control behavior and longevity
Yan, H., Bonasio, R., Simola, D. F., Liebig, J., Berger, S. L., & Reinberg, D. (2015) · Annual Review of Entomology · doi:10.1146/annurev-ento-010814-020803 · Cited by 183
TALENs facilitate targeted genome editing in human cells with high specificity and low cytotoxicity
Mussolino, C., Alzubi, J., Fine, E. J., Morbitzer, R., Cradick, T. J., Lahaye, T., Bao, G., & Cathomen, T. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku305 · Cited by 194
“TALENs, on the other hand, are easier to engineer and seem to combine high cleavage activity with low cytotoxicity, features that have promoted TALENs as a powerful genome engineering tool in the last two years (3).”
BackgroundMethodChromothriptic Cure of WHIM Syndrome
McDermott, D. H., Gao, J., Liu, Q., Siwicki, M. R., Martens, C., Jacobs, P., Velez, D. S., Yim, E., Bryke, C. R., Hsu, N. Y.-H., et al. (2015) · Cell · doi:10.1016/j.cell.2015.01.014 · Cited by 190
The importance of genomic variation for biodiversity, ecosystems and people
Stange, M., Barrett, R. D. H., & Hendry, A. P. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-00288-7 · Cited by 198
Thomazella, D. P. D. T., Brail, Q., Dahlbeck, D., & Staskawicz, B. J. (2016) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/064824 · Cited by 199
“NHEJ repair can cause insertions or deletions (indels) around the DNA breaks, whereas HR can repair double-strand breaks using a homologous repair template (Joung and Sander, 2013; Liu and Fan, 2014; Urnov et al. , 2010).”
BackgroundMethodInfluentialGene-based therapies for neurodegenerative diseases
Sun, J., & Roy, S. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00778-1 · Cited by 194
Targeted genome modification technologies and their applications in crop improvements
Chen, K., & Gao, C. (2013) · Plant Cell Reports · doi:10.1007/s00299-013-1539-6 · Cited by 190
“…since the technique was developed, TALEN technology has been adopted in many organisms including plants such as tobacco (Zhang et al. 2013), rice (Li et al. 2012; Shan et al. 2013a), Brachypodium (Shan et al. 2013a), barley (Wendt et al. 2013), and Arabidopsis (Cermak et al. 2011; Christian et…”
BackgroundMethodRecent advances in the heterologous expression of microbial natural product biosynthetic pathways
Ongley, S. E., Bian, X., Neilan, B. A., & Müller, R. (2013) · Natural Product Reports · doi:10.1039/c3np70034h · Cited by 189
Marker-free coselection for CRISPR-driven genome editing in human cells
Agudelo, D., Duringer, A., Bozoyan, L., Huard, C., Carter, S., Loehr, J., Synodinou, D., Drouin, M., Salsman, J., Dellaire, G., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4265 · Cited by 183
Metadata
- Authors
- Joung, J. K., & Sander, J. D.
- Affiliations
- Harvard University (US)
- Corresponding author
- Joung, J. Keith
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2012-11-21
- Volume
- 14
- Issue
- 1
- Pages
- 49-55
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- PMC
- PMC3547402
- OpenAlex
- W2061184966
- Cited by
- 1,650
- References
- 103
- Citations by year
- 2026: 65 · 2025: 106 · 2024: 128 · 2023: 119 · 2022: 123 · 2021: 102 · 2020: 112 · 2019: 122 · 2018: 114 · 2017: 103 · 2016: 114 · 2015: 159 · 2014: 175 · 2013: 107
- FWCI
- 12.87
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Human Genome Research Institute (P50HG005550)
- National Cancer Institute (T32CA009216)
- National Institute of General Medical Sciences (DP1GM105378, R01GM088040)
- National Center for Chronic Disease Prevention and Health Promotion (DP1 GM105378)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- TALEN, targeted genome editing, engineered nucleases, genetic modification, genetic disease treatment
- MeSH terms
- Animals, Deoxyribonucleases, DNA, DNA-Binding Proteins, Humans, Protein Engineering, Transcriptional Activation, Genome, Protein Structure, Tertiary
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