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clustered regularly interspaced short palindromic repeats

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https://www.readbyqxmd.com/read/27932568/targeting-hif2-in-clear-cell-renal-cell-carcinoma
#1
Hyejin Cho, William G Kaelin
Inactivation of the von Hippel-Lindau tumor-suppressor protein (pVHL) is the signature "truncal" event in clear cell renal cell carcinoma, which is the most common form of kidney cancer. pVHL is part of a ubiquitin ligase the targets the α subunit of the hypoxia-inducible factor (HIF) transcription factor for destruction when oxygen is available. Preclinical studies strongly suggest that deregulation of HIF, and particularly HIF2, drives pVHL-defective renal carcinogenesis. Although HIF2α was classically considered undruggable, structural and chemical work by Rick Bruick and Kevin Gardner at University of Texas Southwestern laid the foundation for the development of small molecule direct HIF2α antagonists (PT2385 and the related tool compound PT2399) by Peloton Therapeutics that block the dimerization of HIF2α with its partner protein ARNT1...
December 8, 2016: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/27924580/using-crispr-cas9-to-study-erk-signaling-in-drosophila
#2
Marta Forés, Aikaterini Papagianni, Laura Rodríguez-Muñoz, Gerardo Jiménez
Genome engineering using the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated nuclease 9 (Cas9) technology is revolutionizing biomedical research. CRISPR-Cas9 enables precise editing of genes in a wide variety of cells and organisms, thereby accelerating molecular studies via targeted mutagenesis, epitope tagging, and other custom genetic modifications. Here, we illustrate the CRISPR-Cas9 methodology by focusing on Capicua (Cic), a nuclear transcriptional repressor directly phosphorylated and inactivated by ERK/MAPK...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27923926/reduced-activity-of-mutant-calcium-dependent-protein-kinase-1-is-compensated-in-plasmodium-falciparum-through-the-action-of-protein-kinase-g
#3
Abhisheka Bansal, Kayode K Ojo, Jianbing Mu, Dustin J Maly, Wesley C Van Voorhis, Louis H Miller
: We used a sensitization approach that involves replacement of the gatekeeper residue in a protein kinase with one with a different side chain. The activity of the enzyme with a bulky gatekeeper residue, such as methionine, cannot be inhibited using bumped kinase inhibitors (BKIs). Here, we have used this approach to study Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1). The methionine gatekeeper substitution, T145M, although it led to a 47% reduction in transphosphorylation, was successfully introduced into the CDPK1 locus using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9...
December 6, 2016: MBio
https://www.readbyqxmd.com/read/27921404/genome-wide-profiling-of-genetic-variation-in-agrobacterium-transformed-rice-plants
#4
Wen-Xu Li, San-Ling Wu, Yan-Hua Liu, Gu-Lei Jin, Hai-Jun Zhao, Long-Jiang Fan, Qing-Yao Shu
Agrobacterium-mediated transformation has been widely used in producing transgenic plants, and was recently used to generate "transgene-clean" targeted genomic modifications coupled with the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas9) system. Although tremendous variation in morphological and agronomic traits, such as plant height, seed fertility, and grain size, was observed in transgenic plants, the underlying mechanisms are not yet well understood, and the types and frequency of genetic variation in transformed plants have not been fully disclosed...
2016: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/27921343/complete-genome-sequence-of-streptococcus-troglodytae-tku31-isolated-from-an-oral-cavity-of-chimpanzee-pan-troglodytes
#5
Masaaki Okamoto, Mariko Naito, Mayu Miyanohara, Susumu Imai, Yoshiaki Nomura, Wataru Saito, Yasuko Momoi, Kazuko Takada, Takako Miyabe-Nishiwaki, Masaki Tomonaga, Nobuhiro Hanada
Streptococcus troglodytae TKU31 was isolated from an oral cavity of chimpanzee (Pan troglodytes), and it is the most closely related species to Streptococcus mutans among the mutans group streptococci. The complete sequence of TKU31 genome consisted of a single circular chromosome that was 2,097,874 base pairs in length, with a G + C content of 37.18%. It possessed a total of 2,082 coding sequences (CDSs), 65 tRNAs and five rRNA operons (15 rRNAs). Two clustered regularly interspaced short palindromic repeats (CRISPRs), six insertion sequences (IS) and two predicted prophage elements were identified...
December 6, 2016: Microbiology and Immunology
https://www.readbyqxmd.com/read/27918485/somatic-cell-nuclear-transfer-followed-by-cripsr-cas9-microinjection-results-in-highly-efficient-genome-editing-in-cloned-pigs
#6
Timothy P Sheets, Chi-Hun Park, Ki-Eun Park, Anne Powell, David M Donovan, Bhanu P Telugu
The domestic pig is an ideal "dual purpose" animal model for agricultural and biomedical research. With the availability of genome editing tools such as clustered regularly interspaced short palindromic repeat (CRISPR) and associated nuclease Cas9 (CRISPR/Cas9), it is now possible to perform site-specific alterations with relative ease, and will likely help realize the potential of this valuable model. In this article, we investigated for the first time a combination of somatic cell nuclear transfer (SCNT) and direct injection of CRISPR/Cas ribonucleoprotein complex targeting GRB10 into the reconstituted oocytes to generate GRB10 ablated Ossabaw fetuses...
December 3, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27917188/crispr-cas9-tool-for-qualitative-and-quantitative-plant-genome-editing
#7
REVIEW
Ali Noman, Muhammad Aqeel, Shuilin He
Recent developments in genome editing techniques have aroused substantial excitement among agricultural scientists. These techniques offer new opportunities for developing improved plant lines with addition of important traits or removal of undesirable traits. Increased adoption of genome editing has been geared by swiftly developing Clustered regularly interspaced short palindromic repeats (CRISPR). This is appearing as driving force for innovative utilization in diverse branches of plant biology. CRISPR-Cas9 mediated genome editing is being used for rapid, easy and efficient alteration of genes among diverse plant species...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27916599/deciphering-communicating-and-engineering-the-crispr-pam
#8
REVIEW
Ryan T Leenay, Chase L Beisel
Clustered regularly interspaced short palindromic repeat (CRISPR) loci and their flanking CRISPR-associated (cas) genes make up RNA-guided, adaptive immune systems in prokaryotes whose effector proteins have become powerful tools for basic research and biotechnology. While the Cas effector proteins are remarkably diverse, they commonly rely on protospacer-adjacent motifs (PAMs) as the first step in target recognition. PAM sequences are known to vary considerably between systems and have proven to be difficult to predict, spurring the need for new tools to rapidly identify and communicate these sequences...
December 1, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27911718/attacking-hiv-1-rna-versus-dna-by-sequence-specific-approaches-rnai-versus-crispr-cas
#9
REVIEW
Elena Herrera-Carrillo, Ben Berkhout
Human immunodeficiency virus type 1 (HIV-1) infection can be effectively controlled by potent antiviral drugs, but this never results in a cure. The patient should therefore take these drugs for the rest of his/her life, which can cause drug-resistance and adverse effects. Therefore, more durable therapeutic strategies should be considered, such as a stable gene therapy to protect the target T cells against HIV-1 infection. The development of potent therapeutic regimens based on the RNA interference (RNAi) and clustered regularly interspaced short palindromic repeats (CRISPR-Cas) mechanisms will be described, which can be delivered by lentiviral vectors...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27908936/genome-editing-technologies-principles-and-applications
#10
REVIEW
Thomas Gaj, Shannon J Sirk, Sai-Lan Shui, Jia Liu
Targeted nucleases have provided researchers with the ability to manipulate virtually any genomic sequence, enabling the facile creation of isogenic cell lines and animal models for the study of human disease, and promoting exciting new possibilities for human gene therapy. Here we review three foundational technologies-clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), and zinc-finger nucleases (ZFNs)...
December 1, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27902801/achieving-plant-crispr-targeting-that-limits-off-target-effects
#11
Jeffrey D Wolt, Kan Wang, Dipali Sashital, Carolyn J Lawrence-Dill
The CRISPR-Cas9 system (clustered regularly interspaced short palindromic repeats with associated Cas9 protein) has been used to generate targeted changes for direct modification of endogenous genes in an increasing number of plant species; but development of plant genome editing has not yet fully considered potential off-target mismatches that may lead to unintended changes within the genome. Assessing the specificity of CRISPR-Cas9 for increasing editing efficiency as well as the potential for unanticipated downstream effects from off-target mutations is an important regulatory consideration for agricultural applications...
November 2016: Plant Genome
https://www.readbyqxmd.com/read/27877187/engineering-plant-immunity-using-crispr-cas9-to-generate-virus-resistance
#12
REVIEW
Syed Shan-E-Ali Zaidi, Manal Tashkandi, Shahid Mansoor, Magdy M Mahfouz
Plant viruses infect many economically important crops, including wheat, cotton, maize, cassava, and other vegetables. These viruses pose a serious threat to agriculture worldwide, as decreases in cropland area per capita may cause production to fall short of that required to feed the increasing world population. Under these circumstances, conventional strategies can fail to control rapidly evolving and emerging plant viruses. Genome-engineering strategies have recently emerged as promising tools to introduce desirable traits in many eukaryotic species, including plants...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27877161/an-enrichment-of-crispr-and-other-defense-related-features-in-marine-sponge-associated-microbial-metagenomes
#13
Hannes Horn, Beate M Slaby, Martin T Jahn, Kristina Bayer, Lucas Moitinho-Silva, Frank Förster, Usama R Abdelmohsen, Ute Hentschel
Many marine sponges are populated by dense and taxonomically diverse microbial consortia. We employed a metagenomics approach to unravel the differences in the functional gene repertoire among three Mediterranean sponge species, Petrosia ficiformis, Sarcotragus foetidus, Aplysina aerophoba and seawater. Different signatures were observed between sponge and seawater metagenomes with regard to microbial community composition, GC content, and estimated bacterial genome size. Our analysis showed further a pronounced repertoire for defense systems in sponge metagenomes...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27857054/type-i-crispr-cas-targets-endogenous-genes-and-regulates-virulence-to-evade-mammalian-host-immunity
#14
Rongpeng Li, Lizhu Fang, Shirui Tan, Min Yu, Xuefeng Li, Sisi He, Yuquan Wei, Guoping Li, Jianxin Jiang, Min Wu
Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems in bacteria and archaea provide adaptive immunity against invading foreign nucleic acids. Previous studies suggest that certain bacteria employ their Type II CRISPR-Cas systems to target their own genes, thus evading host immunity. However, whether other CRISPR-Cas systems have similar functions during bacterial invasion of host cells remains unknown. Here we identify a novel role for Type I CRISPR-Cas systems in evading host defenses in Pseudomonas aeruginosa strain UCBPP-PA14...
December 2016: Cell Research
https://www.readbyqxmd.com/read/27854339/two-novel-myoviruses-from-the-north-of-iraq-reveal-insights-into-clostridium-difficile-phage-diversity-and-biology
#15
Srwa J Rashid, Jakub Barylski, Katherine R Hargreaves, Andrew A Millard, Gurinder K Vinner, Martha R J Clokie
Bacteriophages (phages) are increasingly being explored as therapeutic agents to combat bacterial diseases, including Clostridium difficile infections. Therapeutic phages need to be able to efficiently target and kill a wide range of clinically relevant strains. While many phage groups have yet to be investigated in detail, those with new and useful properties can potentially be identified when phages from newly studied geographies are characterised. Here, we report the isolation of C. difficile phages from soil samples from the north of Iraq...
November 16, 2016: Viruses
https://www.readbyqxmd.com/read/27851729/in-vivo-genome-editing-via-crispr-cas9-mediated-homology-independent-targeted-integration
#16
Keiichiro Suzuki, Yuji Tsunekawa, Reyna Hernandez-Benitez, Jun Wu, Jie Zhu, Euiseok J Kim, Fumiyuki Hatanaka, Mako Yamamoto, Toshikazu Araoka, Zhe Li, Masakazu Kurita, Tomoaki Hishida, Mo Li, Emi Aizawa, Shicheng Guo, Song Chen, April Goebl, Rupa Devi Soligalla, Jing Qu, Tingshuai Jiang, Xin Fu, Maryam Jafari, Concepcion Rodriguez Esteban, W Travis Berggren, Jeronimo Lajara, Estrella Nuñez-Delicado, Pedro Guillen, Josep M Campistol, Fumio Matsuzaki, Guang-Hui Liu, Pierre Magistretti, Kun Zhang, Edward M Callaway, Kang Zhang, Juan Carlos Izpisua Belmonte
Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals)...
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27845770/crispr-cas9-system-as-a-versatile-tool-for-genome-engineering-in-human-cells
#17
REVIEW
Xuelian Wang, Xiumin Huang, Xiuli Fang, Youzhong Zhang, Wanpeng Wang
Targeted nucleases are influential instruments for intervening in genome revision with great accuracy. RNA-guided Cas9 nucleases produced from clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have noticeably altered the means to modify the genomes of distinct organisms. They can be notably used to facilitate effective genome manipulation in eukaryotic cells by clearly detailing a 20-nt targeting sequence inside its directed RNA. We discuss the most recent advancements in the molecular basis of the type II CRISPR/Cas system and encapsulate applications and elements affecting its use in human cells...
November 15, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27845735/deletion-of-pr130-interrupts-cardiac-development-in-zebrafish
#18
Jie Yang, Zuhua Li, Xuedong Gan, Gang Zhai, Jiajia Gao, Chenling Xiong, Xueping Qiu, Xuebin Wang, Zhan Yin, Fang Zheng
Protein phosphatase 2 regulatory subunit B, alpha (PPP2R3A), a regulatory subunit of protein phosphatase 2A (PP2A), is a major serine/threonine phosphatase that regulates crucial function in development and growth. Previous research has implied that PPP2R3A was involved in heart failure, and PR130, the largest transcription of PPP2R3A, functioning in the calcium release of sarcoplasmic reticulum (SR), plays an important role in the excitation-contraction (EC) coupling. To obtain a better understanding of PR130 functions in myocardium and cardiac development, two pr130-deletion zebrafish lines were generated using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system...
November 11, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27842593/easy-regulation-of-metabolic-flux-in-escherichia-coli-using-an-endogenous-type-i-e-crispr-cas-system
#19
Yizhao Chang, Tianyuan Su, Qingsheng Qi, Quanfeng Liang
BACKGROUND: Clustered regularly interspaced short palindromic repeats interference (CRISPRi) is a recently developed powerful tool for gene regulation. In Escherichia coli, the type I CRISPR system expressed endogenously shall be easy for internal regulation without causing metabolic burden in compared with the widely used type II system, which expressed dCas9 as an additional plasmid. RESULTS: By knocking out cas3 and activating the expression of CRISPR-associated complex for antiviral defense (Cascade), we constructed a native CRISPRi system in E...
November 15, 2016: Microbial Cell Factories
https://www.readbyqxmd.com/read/27836208/zebrafish-genome-engineering-using-the-crispr-cas9-system
#20
REVIEW
Mingyu Li, Liyuan Zhao, Patrick S Page-McCaw, Wenbiao Chen
Geneticists have long sought the ability to manipulate vertebrate genomes by directly altering the information encoded in specific genes. The recently discovered clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 endonuclease has the ability to bind single loci within vertebrate genomes and generate double-strand breaks (DSBs) at those sites. These DSBs induce an endogenous DSB repair response that results in small insertions or deletions at the targeted site. Alternatively, a template can be supplied, in which case homology-directed repair results in the generation of engineered alleles at the break site...
December 2016: Trends in Genetics: TIG
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