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Transcription activator-like effectors

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https://www.readbyqxmd.com/read/28337020/delivery-technologies-for-genome-editing
#1
REVIEW
Hao Yin, Kevin J Kauffman, Daniel G Anderson
With the recent development of CRISPR technology, it is becoming increasingly easy to engineer the genome. Genome-editing systems based on CRISPR, as well as transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases (ZFNs), are becoming valuable tools for biomedical research, drug discovery and development, and even gene therapy. However, for each of these systems to effectively enter cells of interest and perform their function, efficient and safe delivery technologies are needed. This Review discusses the principles of biomacromolecule delivery and gene editing, examines recent advances and challenges in non-viral and viral delivery methods, and highlights the status of related clinical trials...
March 24, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28336611/self-assembly-of-genetically-encoded-dna-protein-hybrid-nanoscale-shapes
#2
Florian Praetorius, Hendrik Dietz
We describe an approach to bottom-up fabrication that allows integration of the functional diversity of proteins into designed three-dimensional structural frameworks. A set of custom staple proteins based on transcription activator-like effector proteins folds a double-stranded DNA template into a user-defined shape. Each staple protein is designed to recognize and closely link two distinct double-helical DNA sequences at separate positions on the template. We present design rules for constructing megadalton-scale DNA-protein hybrid shapes; introduce various structural motifs, such as custom curvature, corners, and vertices; and describe principles for creating multilayer DNA-protein objects with enhanced rigidity...
March 24, 2017: Science
https://www.readbyqxmd.com/read/28334759/highly-efficient-biallelic-genome-editing-of-human-es-ips-cells-using-a-crispr-cas9-or-talen-system
#3
Kazuo Takayama, Keisuke Igai, Yasuko Hagihara, Rina Hashimoto, Morifumi Hanawa, Tetsushi Sakuma, Masashi Tachibana, Fuminori Sakurai, Takashi Yamamoto, Hiroyuki Mizuguchi
Genome editing research of human ES/iPS cells has been accelerated by clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9) and transcription activator-like effector nucleases (TALEN) technologies. However, the efficiency of biallelic genetic engineering in transcriptionally inactive genes is still low, unlike that in transcriptionally active genes. To enhance the biallelic homologous recombination efficiency in human ES/iPS cells, we performed screenings of accessorial genes and compounds...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28333384/transcriptional-regulation-of-adipogenesis
#4
Paula Mota de Sá, Allison J Richard, Hardy Hang, Jacqueline M Stephens
Adipocytes are the defining cell type of adipose tissue. Once considered a passive participant in energy storage, adipose tissue is now recognized as a dynamic organ that contributes to several important physiological processes, such as lipid metabolism, systemic energy homeostasis, and whole-body insulin sensitivity. Therefore, understanding the mechanisms involved in its development and function is of great importance. Adipocyte differentiation is a highly orchestrated process which can vary between different fat depots as well as between the sexes...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28331099/interferon-inducible-oligoadenylate-synthetase-like-protein-acts-as-an-antiviral-effector-against-classical-swine-fever-virus-via-the-mda5-mediated-type-i-interferon-signaling-pathway
#5
Lian-Feng Li, Jiahui Yu, Yuexiu Zhang, Qian Yang, Yongfeng Li, Lingkai Zhang, Jinghan Wang, Su Li, Yuzi Luo, Yuan Sun, Hua-Ji Qiu
Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), which poses a serious threat to the global pig industry. Interferons (IFNs) and IFN-stimulated genes (ISGs) play a key role in host antiviral defense. We have previously screened the porcine 2' -5' -oligoadenylate synthase-like protein (pOASL) as a potential anti-CSFV ISG using a reporter CSFV. This study aimed to clarify the underlying antiviral mechanism of pOASL against CSFV. We confirmed that CSFV replication was significantly suppressed in lentivirus-delivered, pOASL-overexpressing PK-15 cells, whereas silencing the expression of endogenous pOASL by small interfering RNAs markedly enhanced CSFV growth...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28320954/cerberus-nodal-lefty-pitx-signaling-cascade-controls-left-right-asymmetry-in-amphioxus
#6
Guang Li, Xian Liu, Chaofan Xing, Huayang Zhang, Sebastian M Shimeld, Yiquan Wang
Many bilaterally symmetrical animals develop genetically programmed left-right asymmetries. In vertebrates, this process is under the control of Nodal signaling, which is restricted to the left side by Nodal antagonists Cerberus and Lefty. Amphioxus, the earliest diverging chordate lineage, has profound left-right asymmetry as a larva. We show that Cerberus, Nodal, Lefty, and their target transcription factor Pitx are sequentially activated in amphioxus embryos. We then address their function by transcription activator-like effector nucleases (TALEN)-based knockout and heat-shock promoter (HSP)-driven overexpression...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28318979/a-phytophthora-effector-manipulates-host-histone-acetylation-and-reprograms-defense-gene-expression-to-promote-infection
#7
Liang Kong, Xufang Qiu, Jiangang Kang, Yang Wang, Han Chen, Jie Huang, Min Qiu, Yao Zhao, Guanghui Kong, Zhenchuan Ma, Yan Wang, Wenwu Ye, Suomeng Dong, Wenbo Ma, Yuanchao Wang
Immune response during pathogen infection requires extensive transcription reprogramming. A fundamental mechanism of transcriptional regulation is histone acetylation. However, how pathogens interfere with this process to promote disease remains largely unknown. Here we demonstrate that the cytoplasmic effector PsAvh23 produced by the soybean pathogen Phytophthora sojae acts as a modulator of histone acetyltransferase (HAT) in plants. PsAvh23 binds to the ADA2 subunit of the HAT complex SAGA and disrupts its assembly by interfering with the association of ADA2 with the catalytic subunit GCN5...
March 11, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28304228/induction-of-xa10-like-genes-in-rice-cultivar-nipponbare-confers-disease-resistance-to-rice-bacterial-blight
#8
Jun Wang, Dongsheng Tian, Keyu Gu, Xiaobei Yang, Lanlan Wang, Xuan Zeng, Zhongchao Yin
Bacterial blight of rice, caused by Xanthomonas oryzae pv. oryzae, is one of the most destructive bacterial diseases throughout the major rice growing regions in the world. The rice disease resistance (R) genes Xa10 confers race-specific disease resistance to X. oryzae pv. oryzae strains that deliver the corresponding transcription activator-like (TAL) effectors AvrXa10. Upon bacterial infection, AvrXa10 binds specifically to the effector binding element (EBE) in the promoter of the R gene and activates its expression...
March 17, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28301511/dissection-of-tale-dependent-gene-activation-reveals-that-they-induce-transcription-cooperatively-and-in-both-orientations
#9
Jana Streubel, Heidi Baum, Jan Grau, Johannes Stuttman, Jens Boch
Plant-pathogenic Xanthomonas bacteria inject transcription activator-like effector proteins (TALEs) into host cells to specifically induce transcription of plant genes and enhance susceptibility. Although the DNA-binding mode is well-understood it is still ambiguous how TALEs initiate transcription and whether additional promoter elements are needed to support this. To systematically dissect prerequisites for transcriptional initiation the activity of one TALE was compared on different synthetic Bs4 promoter fragments...
2017: PloS One
https://www.readbyqxmd.com/read/28288698/crispr-system-for-genome-engineering-the-application-for-autophagy-study
#10
Jianzhou Cui, Shirley Jia Li Chew, Yin Shi, Zhiyuan Gong, Han-Ming Shen
CRISPR/Cas9 is the latest tool introduced in the field of genome engineering and is so far the best genome-editing tool as compared to its precedents such as, meganucleases, zinc finger nucleases (ZFNs) and transcription activator-like effectors (TALENs). The simple design and assembly of the CRISPR/Cas9 system makes genome editing easy to perform as it uses small guide RNAs that correspond to their DNA targets for high efficiency editing. This has helped open the doors for multiplexible genome targeting in many species that were intractable using old genetic perturbation techniques...
March 14, 2017: BMB Reports
https://www.readbyqxmd.com/read/28288138/muc1-c-integrates-pd-l1-induction-with-repression-of-immune-effectors-in-non-small-cell-lung-cancer
#11
A Bouillez, H Rajabi, C Jin, M Samur, A Tagde, M Alam, M Hiraki, T Maeda, X Hu, D Adeegbe, S Kharbanda, K-K Wong, D Kufe
Immunotherapeutic approaches, particularly programmed death 1/programmed death ligand 1 (PD-1/PD-L1) blockade, have improved the treatment of non-small-cell lung cancer (NSCLC), supporting the premise that evasion of immune destruction is of importance for NSCLC progression. However, the signals responsible for upregulation of PD-L1 in NSCLC cells and whether they are integrated with the regulation of other immune-related genes are not known. Mucin 1 (MUC1) is aberrantly overexpressed in NSCLC, activates the nuclear factor-κB (NF-κB) p65ZEB1 pathway and confers a poor prognosis...
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28284693/the-effects-of-cell-death-inducing-dna-fragmentation-factor-%C3%AE-like-effector-c-on-milk-lipid-synthesis-in-mammary-glands-of-dairy-cows
#12
Yang Yang, Ye Lin, Xiaoyu Duan, He Lv, Weinan Xing, Qingzhang Li, Xuejun Gao, Xiaoming Hou
Adequate lipid synthesis by the mammary gland during lactation is essential for the survival of mammalian offspring. Cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC) is a lipid droplet-associated protein and functions to promote lipid accumulation and inhibit lipolysis in mice and human adipocytes. However, the function of CIDEC in regulation of milk lipid synthesis in dairy cow mammary gland remains largely unknown. In this study, 6 multiparous Holstein cows (parity = 3) in early lactation were allocated to high-fat milk (milk yield 33...
March 8, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28281540/t-ell-tale-signs-of-aging
#13
Reshma Taneja, Brian K Kennedy
Transcriptional activator-like effectors (TALEs) have emerged as powerful tools for genome editing. A recent study published by Cell Research reports that fusion of thioredoxin to TALEs unlocks their full potential in live-cell imaging to accurately analyze genome instability, telomere attrition and epigenetic alterations that are hallmarks of aging.
March 10, 2017: Cell Research
https://www.readbyqxmd.com/read/28279806/fish-skeletal-muscle-tissue-is-an-important-focus-of-immune-reactions-during-pathogen-infection
#14
Cristián A Valenzuela, Rodrigo Zuloaga, Matías Poblete-Morales, Tamara Vera-Tobar, Luis Mercado, Ruben Avendaño-Herrera, Juan Antonio Valdés, Alfredo Molina
Skeletal muscle in mammals can express and secrete immune-related molecules during pathogen infection. Despite in fish is known that classical immune tissues participate in innate immunity, the role of skeletal muscle in this function is poorly understood. To determine the immunocompetence of fish skeletal muscle, juvenile fine flounder (Paralichthys adpersus) were challenged with Vibrio ordalii. Different Toll-like receptors, pro-inflammatory cytokines (TNFα, Il-1β, and IL-8), and immune-effector molecules (NKEF and the antimicrobial peptides hepcidin and LEAP-2) were analyzed...
March 7, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28275380/genetic-transformation-and-genomic-resources-for-next-generation-precise-genome-engineering-in-vegetable-crops
#15
REVIEW
Teodoro Cardi, Nunzio D'Agostino, Pasquale Tripodi
In the frame of modern agriculture facing the predicted increase of population and general environmental changes, the securement of high quality food remains a major challenge to deal with. Vegetable crops include a large number of species, characterized by multiple geographical origins, large genetic variability and diverse reproductive features. Due to their nutritional value, they have an important place in human diet. In recent years, many crop genomes have been sequenced permitting the identification of genes and superior alleles associated with desirable traits...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28272984/exogenous-gene-integration-mediated-by-genome-editing-technologies-in-zebrafish
#16
Hitoshi Morita, Kiyohito Taimatsu, Kanoko Yanagi, Atsuo Kawahara
Genome editing technologies, such as transcription activator-like effector nuclease (TALEN) and the clustered regularly interspaced short palindromic repeat (CRISPR)/ CRISPR-associated protein (Cas) systems, can induce DNA double-strand breaks (DSBs) at the targeted genomic locus, leading to frameshift-mediated gene disruption in the process of DSB repair. Recently, the technology-induced DSBs followed by DSB repairs are applied to integrate exogenous genes into the targeted genomic locus in various model organisms...
March 8, 2017: Bioengineered
https://www.readbyqxmd.com/read/28270008/gene-delivery-to-the-lungs-pulmonary-gene-therapy-for-cystic-fibrosis
#17
Ilia Villate-Beitia, Jon Zarate, Gustavo Puras, José Luis Pedraz
Cystic fibrosis (CF) is a monogenic autosomal recessive disorder where the defective gene, the cystic fibrosis transmembrane conductance regulator (CFTR), is well identified. Moreover, the respiratory tract can be targeted through noninvasive aerosolized formulations for inhalation. Therefore, gene therapy is considered a plausible strategy to address this disease. Conventional gene therapy strategies rely on the addition of a correct copy of the CFTR gene into affected cells in order to restore the channel activity...
March 7, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28261237/progress-in-genome-editing-technology-and-its-application-in-plants
#18
REVIEW
Kai Zhang, Nadia Raboanatahiry, Bin Zhu, Maoteng Li
Genome editing technology (GET) is a versatile approach that has progressed rapidly as a mechanism to alter the genotype and phenotype of organisms. However, conventional genome modification using GET cannot satisfy current demand for high-efficiency and site-directed mutagenesis, retrofitting of artificial nucleases has developed into a new avenue within this field. Based on mechanisms to recognize target genes, newly-developed GETs can generally be subdivided into three cleavage systems, protein-dependent DNA cleavage systems (i...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28258666/the-role-of-gene-editing-in-neurodegenerative-diseases
#19
Hueng-Chuen Fan, Ching-Shiang Chi, Yih-Jing Lee, Jeng-Dau Tsai, Shinn-Zong Lin, Horng-Jyh Harn
Neurodegenerative diseases (NDs), at least including Alzheimer's, Huntington's, and Parkinson's diseases, have become the most dreaded maladies because of no precise diagnostic tools or definite treatments for these debilitating diseases. The increased prevalence and a substantial impact on the social-economic and medical care of NDs propel governments to develop policies to counteract the impact. Although the etiologies of NDs are still unknown, growing evidence suggests that genetic, cellular and circuit alternations may cause the generation of abnormal misfolded proteins, which uncontrolledly accumulate to damage eventually overwhelms the protein-disposal mechanisms of these neurons, leading to a common pathological feature of NDs...
March 3, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28257996/linking-of-mpges-1-and-inos-activates-stem-like-phenotype-in-egfr-driven-epithelial-tumor-cells
#20
Erika Terzuoli, Federica Finetti, Filomena Costanza, Antonio Giachetti, Marina Ziche, Sandra Donnini
Inflammatory prostaglandin E-2 (PGE-2) favors cancer progression in epithelial tumors characterized by persistent oncogene input. However, its effects on tumor cell stemness are poorly understood at molecular level. Here we describe two epithelial tumor cells A431 and A459, originating from human lung and skin tumors, in which epithelial growth factor (EGF) induces sequential up-regulation of mPGES-1 and iNOS enzymes, producing an inflammatory intracellular milieu. We demonstrated that concerted action of EGF, mPGES-1 and iNOS causes sharp changes in cell phenotype demonstrated by acquisition of stem-cell features and activation of the epithelial-mesenchymal transition (EMT)...
March 1, 2017: Nitric Oxide: Biology and Chemistry
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