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https://www.readbyqxmd.com/read/29352444/activation-of-the-anti-aging-and-cognition-enhancing-gene-klotho-by-crispr-dcas9-transcriptional-effector-complex
#1
Ci-Di Chen, Ella Zeldich, Yuexuan Li, Andrea Yuste, Carmela R Abraham
Multiple lines of evidence show that the anti-aging and cognition-enhancing protein Klotho fosters neuronal survival, increases the anti-oxidative stress defense, and promotes remyelination of demyelinated axons. Thus, upregulation of the Klotho gene can potentially alleviate the symptoms and/or prevent the progression of age-associated neurodegenerative diseases such as Alzheimer's disease and demyelinating diseases such as multiple sclerosis. Here we used a CRISPR-dCas9 complex to investigate single-guide RNA (sgRNA) targeting the Klotho promoter region for efficient transcriptional activation of the Klotho gene...
January 19, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29352202/publisher-correction-correction-of-a-disease-mutation-using-crispr-cas9-assisted-genome-editing-in-japanese-black-cattle
#2
Mitsumi Ikeda, Shuichi Matsuyama, Satoshi Akagi, Katsuhiro Ohkoshi, Sho Nakamura, Shiori Minabe, Koji Kimura, Misa Hosoe
A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348648/specific-cyclic-adp-ribose-phosphohydrolase-obtained-by-mutagenic-engineering-of-mn2-dependent-adp-ribose-cdp-alcohol-diphosphatase
#3
João Meireles Ribeiro, José Canales, Alicia Cabezas, Joaquim Rui Rodrigues, Rosa María Pinto, Iralis López-Villamizar, María Jesús Costas, José Carlos Cameselle
Cyclic ADP-ribose (cADPR) is a messenger for Ca2+ mobilization. Its turnover is believed to occur by glycohydrolysis to ADP-ribose. However, ADP-ribose/CDP-alcohol diphosphatase (ADPRibase-Mn) acts as cADPR phosphohydrolase with much lower efficiency than on its major substrates. Recently, we showed that mutagenesis of human ADPRibase-Mn at Phe37, Leu196 and Cys253 alters its specificity: the best substrate of the mutant F37A + L196F + C253A is cADPR by a short difference, Cys253 mutation being essential for cADPR preference...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348585/a-surrogate-reporter-system-for-multiplexable-evaluation-of-crispr-cas9-in-targeted-mutagenesis
#4
Hongmin Zhang, Yuexin Zhou, Yinan Wang, Yige Zhao, Yeting Qiu, Xinyi Zhang, Di Yue, Zhuo Zhou, Wensheng Wei
Engineered nucleases in genome editing manifest diverse efficiencies at different targeted loci. There is therefore a constant need to evaluate the mutation rates at given loci. T7 endonuclease 1 (T7E1) and Surveyor mismatch cleavage assays are the most widely used methods, but they are labour and time consuming, especially when one must address multiple samples in parallel. Here, we report a surrogate system, called UDAR (Universal Donor As Reporter), to evaluate the efficiency of CRISPR/Cas9 in targeted mutagenesis...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29347847/combining-cell-and-gene-therapy-to-advance-cardiac-regeneration
#5
Pina Marotta, Eleonora Cianflone, Iolanda Aquila, Carla Vicinanza, Mariangela Scalise, Fabiola Marino, Teresa Mancuso, Michele Torella, Ciro Indolfi, Daniele Torella
The characterization of multipotent endogenous cardiac stem cells (eCSCs) and the breakthroughs of somatic cell reprogramming to boost cardiomyocyte replacement have fostered the prospect of achieving functional heart repair/regeneration. Areas covered: Allogeneic CSC therapy through its paracrine stimulation of the endogenous resident reparative/regenerative process produces functional meaningful myocardial regeneration in pre-clinical porcine myocardial infarction models and is currently tested in the first-in-man human trial...
January 19, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29347817/biochemical-basis-of-apobec3-deoxycytidine-deaminase-activity-on-diverse-dna-substrates
#6
Madison B Adolph, Robin P Love, Linda Chelico
The Apolipoprotein B mRNA editing complex (APOBEC) family of enzymes are single-stranded polynucleotide cytidine deaminases. These enzymes catalyze the deamination of cytidine in RNA or single-stranded DNA, which forms uracil. From this eleven member enzyme family in humans, the deamination of single-stranded DNA by the seven APOBEC3 family members are considered here. The APOBEC3 family has many roles such as, restricting endogenous and exogenous retrovirus replication and retrotransposon insertion events and reducing DNA-induced inflammation...
January 18, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29346757/p53-suppresses-metabolic-stress-induced-ferroptosis-in-cancer-cells
#7
Amy Tarangelo, Leslie Magtanong, Kathryn T Bieging-Rolett, Yang Li, Jiangbin Ye, Laura D Attardi, Scott J Dixon
How cancer cells respond to nutrient deprivation remains poorly understood. In certain cancer cells, deprivation of cystine induces a non-apoptotic, iron-dependent form of cell death termed ferroptosis. Recent evidence suggests that ferroptosis sensitivity may be modulated by the stress-responsive transcription factor and canonical tumor suppressor protein p53. Using CRISPR/Cas9 genome editing, small-molecule probes, and high-resolution, time-lapse imaging, we find that stabilization of wild-type p53 delays the onset of ferroptosis in response to cystine deprivation...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29345746/history-of-genome-editing-in-yeast
#8
Marcin G Fraczek, Samina Naseeb, Daniela Delneri
For thousands of years humans have used the budding yeast Saccharomyces cerevisiae for production of bread and alcohol, however only for the last 30-40 years our understanding of the yeast biology has dramatically increased enabling us to modify its genome. Although S. cerevisiae has been the main focus of many research groups, other non-conventional yeasts have also been studied and exploited for biotechnological purposes. Our experiments and knowledge have evolved from recombination, to high-throughput PCR based transformations, to highly accurate CRISPR methods, in order to alter yeast traits for either research of industrial purposes...
January 18, 2018: Yeast
https://www.readbyqxmd.com/read/29345375/understanding-the-regulation-of-apobec3-expression-current-evidence-and-much-to-learn
#9
REVIEW
Daniela Angela Covino, Maria Cristina Gauzzi, Laura Fantuzzi
The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of cytosine deaminases plays crucial roles in innate immunity through the ability of restricting viral replication by deamination and mutation of viral genomes. The antiviral function of these proteins was first discovered when research in the field of HIV infection revealed that one member of the family, namely APOBEC3G, restricts HIV infection in T lymphocytes and that the viral infectivity factor protein drives the proteosomal degradation of this enzyme, thus overriding its antiviral function...
December 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345014/human-induced-pluripotent-stem-cell-models-of-retinitis-pigmentosa
#10
REVIEW
Ana Artero Castro, Dunja Lukovic, Pavla Jendelova, Slaven Erceg
Hereditary retinal dystrophies, specifically retinitis pigmentosa (RP) are clinically and genetically heterogeneous diseases affecting primarily retinal cells and retinal pigment epithelial (RPE) cells with blindness as a final outcome. Understanding the pathogenicity behind these diseases has been largely precluded by the unavailability of affected tissue from patients, large genetic heterogeneity and animal models that do not faithfully represent some human diseases. A landmark discovery of human induced pluripotent stem cells (hiPSC) permitted the derivation of patient-specific cells...
January 18, 2018: Stem Cells
https://www.readbyqxmd.com/read/29344851/the-evolution-of-crispr-cas9-and-their-cousins-hope-or-hype
#11
REVIEW
Kulbhushan Chaudhary, Anirudha Chattopadhyay, Dharmendra Pratap
Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system allows biologists to edit genomic DNA of any cell in precise and specific way, entailing great potential for crop improvement, drug development and gene therapy. The system involves a nuclease (Cas9) and a designed guide RNA that are involved in wide range of applications such as genome modification, transcriptional modulation, genomic loci marking and RNA tracking. The limitation of the technique, in view of resistance of thymidine-rich genome to Cas9 cleavage, has now been overcome by the use of Cpf1 nuclease...
January 17, 2018: Biotechnology Letters
https://www.readbyqxmd.com/read/29344676/application-of-genome-editing-techniques-in-immunology
#12
REVIEW
Agata O Zych, Malgorzata Bajor, Radoslaw Zagozdzon
The idea of using the effector immune cells to specifically fight cancer has recently evolved into an exciting concept of adoptive cell therapies. Indeed, genetically engineered T cells expressing on their surface recombinant, cancer-targeted receptors have been shown to induce promising response in oncological patients. However, in addition to exogenous expression of such receptors, there is also a need for disruption of certain genes in the immune cells to achieve more potent disease-targeted actions, to produce universal chimeric antigen receptor-based therapies or to study the signaling pathways in detail...
January 17, 2018: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/29344267/break-breast-cancer-addiction-by-crispr-cas9-genome-editing
#13
REVIEW
Haitao Yang, MariaLynn Jaeger, Averi Walker, Daniel Wei, Katie Leiker, Tao Weitao
Breast cancer is the leading diagnosed cancer for women globally. Evolution of breast cancer in tumorigenesis, metastasis and treatment resistance appears to be driven by the aberrant gene expression and protein degradation encoded by the cancer genomes. The uncontrolled cancer growth relies on these cellular events, thus constituting the cancerous programs and rendering the addiction towards them. These programs are likely the potential anticancer biomarkers for Personalized Medicine of breast cancer. This review intends to delineate the impact of the CRSPR/Cas-mediated genome editing in identification and validation of these anticancer biomarkers...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29344087/determination-of-the-native-features-of-the-exoglucanase-cel48s-from-clostridium-thermocellum
#14
Ya-Jun Liu, Shiyue Liu, Sheng Dong, Renmin Li, Yingang Feng, Qiu Cui
Background: Clostridium thermocellum is considered one of the most efficient natural cellulose degraders because of its cellulosomal system. As the major exoglucanase of cellulosome in C. thermocellum, Cel48S plays key roles and influences the activity and features of cellulosome to a great extent. Thus, it is of great importance to reveal the enzymatic features of Cel48S. However, Cel48S has not been well performed due to difficulties in purifying either recombinant or native Cel48S proteins...
2018: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29343412/implementing-genome-driven-personalized-cardiology-in-clinical-practice
#15
REVIEW
Ares Pasipoularides
Genomics designates the coordinated investigation of a large number of genes in the context of a biological process or disease. It may be long before we attain comprehensive understanding of the genomics of common complex cardiovascular diseases (CVDs) such as inherited cardiomyopathies, valvular diseases, primary arrhythmogenic conditions, congenital heart syndromes, hypercholesterolemia and atherosclerotic heart disease, hypertensive syndromes, and heart failure with preserved/reduced ejection fraction. Nonetheless, as genomics is evolving rapidly, it is constructive to survey now pertinent concepts and breakthroughs...
January 14, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29343191/thermophilic-xylanases-from-bench-to-bottle
#16
Abdul Basit, Junquan Liu, Kashif Rahim, Wei Jiang, Huiqiang Lou
Lignocellulosic biomass is a valuable raw material. As technology has evolved, industrial interest in new ways to take advantage of this raw material has grown. Biomass is treated with different microbial cells or enzymes under ideal industrial conditions to produce the desired products. Xylanases are the key enzymes that degrade the xylosidic linkages in the xylan backbone of the biomass, and commercial enzymes are categorized into different glycoside hydrolase families. Thermophilic microorganisms are excellent sources of industrially relevant thermostable enzymes that can withstand the harsh conditions of industrial processing...
January 17, 2018: Critical Reviews in Biotechnology
https://www.readbyqxmd.com/read/29340115/hypermutation-and-microsatellite-instability-in-gastrointestinal-cancers
#17
REVIEW
Kizuki Yuza, Masayuki Nagahashi, Satoshi Watanabe, Kazuaki Takabe, Toshifumi Wakai
Recent progress in cancer genome analysis using next-generation sequencing has revealed a high mutation burden in some tumors. The particularly high rate of somatic mutation in these tumors correlates with the generation of neo-antigens capable of eliciting an immune response. Identification of hypermutated tumors is therefore clinically valuable for selecting patients suitable for immunotherapy treatment. There are several known causes of hypermutation in tumors, such as ultraviolet light in melanoma, tobacco smoke in lung cancer, and excessive APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) activity in breast and gastric cancer...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339069/multiple-homologous-genes-knockout-ko-by-crispr-cas9-system-in-rabbit
#18
Huan Liu, Tingting Sui, Di Liu, Tingjun Liu, Mao Chen, Jichao Deng, Yuanyuan Xu, Zhanjun Li
The CRISPR/Cas9 system is a highly efficient and convenient genome editing tool, which has been widely used for single or multiple gene mutation in a variety of organisms. Disruption of multiple homologous genes, which have similar DNA sequences and gene function, is required for the study of the desired phenotype. In this study, to test whether the CRISPR/Cas9 system works on the mutation of multiple homologous genes, a single guide RNA (sgRNA) targeting three fucosyltransferases encoding genes (FUT1, FUT2 and SEC1) was designed...
January 12, 2018: Gene
https://www.readbyqxmd.com/read/29338433/in-vivo-ovarian-cancer-gene-therapy-using-crispr-cas9-system
#19
Zhi-Yao He, Ya-Guang Zhang, Yu-Han Yang, Cui-Cui Ma, Ping Wang, Wei Du, Ling Li, Rong Xiang, Xiang-Rong Song, Xia Zhao, Shaohua Yao, Yu-Quan Wei
CRISPR-Cas9 genome editing technology holds great promise for the field of human gene therapy. However, deficiency of safe and effective delivery systems restricts the biomedical application of CRISPR-Cas9 technique. Here, we use a folate receptor-targeted liposome (F-LP) to deliver a CRISPR plasmid DNA co-expressing Cas9 and single guide RNA targeting the DNA methyltransferase 1 (DNMT1) gene of ovarian cancer. F-LP binds CRISPR plasmid (gDNMT1) efficiently and the formed lipoplex (F-LP/gDNMT1) is stable and safe for injection...
January 16, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29337866/crispr-cas-targeting-of-host-genes-as-an-antiviral-strategy
#20
REVIEW
Shuliang Chen, Xiao Yu, Deyin Guo
Currently, a new gene editing tool-the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated (Cas) system-is becoming a promising approach for genetic manipulation at the genomic level. This simple method, originating from the adaptive immune defense system in prokaryotes, has been developed and applied to antiviral research in humans. Based on the characteristics of virus-host interactions and the basic rules of nucleic acid cleavage or gene activation of the CRISPR-Cas system, it can be used to target both the virus genome and host factors to clear viral reservoirs and prohibit virus infection or replication...
January 16, 2018: Viruses
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