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https://www.readbyqxmd.com/read/28527665/therapeutic-editing-of-hepatocyte-genome-in-vivo
#1
REVIEW
Marina Ruiz de Galarreta, Amaia Lujambio
The recent development of gene editing platforms enables making precise changes in the genome of eukaryotic cells. Programmable nucleases, such as meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)-associated nucleases, have revolutionized the way research is conducted as they facilitate the rapid production of mutant or knock-out cellular and animal models. These same genetic tools can potentially be applied to cure or alleviate a variety of diseases, including genetic diseases that lack an efficient therapy...
May 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28527116/genome-editing-in-drosophila-melanogaster-from-basic-genome-engineering-to-the-multipurpose-crispr-cas9-system
#2
REVIEW
Xingjie Ren, Kristof Holsteens, Haiyi Li, Jin Sun, Yifan Zhang, Lu-Ping Liu, Qingfei Liu, Jian-Quan Ni
Nowadays, genome editing tools are indispensable for studying gene function in order to increase our knowledge of biochemical processes and disease mechanisms. The extensive availability of mutagenesis and transgenesis tools make Drosophila melanogaster an excellent model organism for geneticists. Early mutagenesis tools relied on chemical or physical methods, ethyl methane sulfonate (EMS) and X-rays respectively, to randomly alter DNA at a nucleotide or chromosomal level. Since the discovery of transposable elements and the availability of the complete fly genome, specific genome editing tools, such as P-elements, zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), have undergone rapid development...
May 1, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28525759/modeling-rett-syndrome-using-talen-edited-mecp2-mutant-cynomolgus-monkeys
#3
Yongchang Chen, Juehua Yu, Yuyu Niu, Dongdong Qin, Hailiang Liu, Gang Li, Yingzhou Hu, Jiaojian Wang, Yi Lu, Yu Kang, Yong Jiang, Kunhua Wu, Siguang Li, Jingkuan Wei, Jing He, Junbang Wang, Xiaojing Liu, Yuping Luo, Chenyang Si, Raoxian Bai, Kunshan Zhang, Jie Liu, Shaoyong Huang, Zhenzhen Chen, Shuang Wang, Xiaoying Chen, Xinhua Bao, Qingping Zhang, Fuxing Li, Rui Geng, Aibin Liang, Dinggang Shen, Tianzi Jiang, Xintian Hu, Yuanye Ma, Weizhi Ji, Yi Eve Sun
Gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. Here, we report detailed genotypes and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys serving as a model for a neurodevelopmental disorder, Rett syndrome (RTT), which is caused by loss-of-function mutations in the human MECP2 gene. Male mutant monkeys were embryonic lethal, reiterating that RTT is a disease of females. Through a battery of behavioral analyses, including primate-unique eye-tracking tests, in combination with brain imaging via MRI, we found a series of physiological, behavioral, and structural abnormalities resembling clinical manifestations of RTT...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28522548/a-multi-purpose-toolkit-to-enable-advanced-genome-engineering-in-plants
#4
Tomas Cermak, Shaun J Curtin, Javier Gil-Humanes, Radim Čegan, Thomas J Y Kono, Eva Konečná, Joseph J Belanto, Colby G Starker, Jade W Mathre, Rebecca L Greenstein, Daniel F Voytas
We report a comprehensive toolkit that enables targeted, specific modification of monocot and dicot genomes using a variety of genome engineering approaches. Our reagents, based on TALENs and the CRISPR/Cas9 system, are systematized for fast, modular cloning and accommodate diverse regulatory sequences to drive reagent expression. Vectors are optimized to create either single or multiple gene knockouts and large chromosomal deletions. Moreover, integration of geminivirus-based vectors enables precise gene editing through homologous recombination...
May 18, 2017: Plant Cell
https://www.readbyqxmd.com/read/28521708/implementation-and-evaluation-of-a-technology-system-to-improve-safety-in-the-pharmacotherapeutic-process-in-oncohematology
#5
Maria Teresa Aznar Saliente, Mauricio Martínez Ramírez, Maria Amparo Talens Bolós, Paola Herraiz Robles, Nuria Bujadón Querejeta, Maria Dolores Camacho Romera, Laia Pons M Artínez, Manuel Bonete Sánchez, Borja Marcos Ribes, Maria Teresa Martínez Lazcano, Francisco Martínez Granados
OBJECTIVE The objective of the study was to describe the process of implementing a technology system to improve safety and quality in all processes involved in the treatment with parenteral antineoplastic agents within an interdisciplinary team and to analyze the errors detected and avoided thanks to this system at the different stages of the process. MATERIALS AND METHODS Observational and retrospective study where the implementation of an expert technology system in all phases of the therapeutic process is described: prescription, validation, preparation and administration of drugs, in which errors found in the different phases are analysed...
May 18, 2017: Current Drug Safety
https://www.readbyqxmd.com/read/28514765/bmx-etk-promotes-cell-proliferation-and-tumorigenicity-of-cervical-cancer-cells-through-pi3k-akt-mtor-and-stat3-pathways
#6
Yuanyuan Li, Nan Cui, Peng-Sheng Zheng, Wen-Ting Yang
Bone marrow X-linked kinase (BMX, also known as Etk) has been reported to be involved in cell proliferation, differentiation, apoptosis, migration and invasion in several types of tumors, but its role in cervical carcinoma remains poorly understood. In this study, we showed that BMX expression exhibits a gradually increasing trend from normal cervical tissue to cervical cancer in situ and then to invasive cervical cancer tissue. Through BMX-IN-1, a potent and irreversible BMX kinase inhibitor, inhibited the expression of BMX, the cell proliferation was significantly decreased...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28501230/integrative-medicine-and-mood-emotions-and-mental-health
#7
REVIEW
Anuj K Shah, Roman Becicka, Mary R Talen, Deborah Edberg, Sreela Namboodiri
An integrative approach to individuals with mood, emotional or mental health concerns involves a comprehensive model of care that is person-centered. Integrative medicine builds on a patient's personal meaning and goals (spiritual aspects) and includes herbal therapies, nutritional support, movement and physical manipulative therapies, mindfulness, relaxation strategies, and psychotherapies.
June 2017: Primary Care
https://www.readbyqxmd.com/read/28499832/versatile-and-precise-gene-targeting-strategies-for-functional-studies-in-mammalian-cell-lines
#8
REVIEW
M Wassef, A Luscan, A Battistella, S Le Corre, H Li, M R Wallace, M Vidaud, R Margueron
The advent of programmable nucleases such as ZFNs, TALENs and CRISPR/Cas9 has brought the power of genetic manipulation to widely used model systems. In mammalian cells, nuclease-mediated DNA double strand break is mainly repaired through the error-prone non-homologous end-joining (NHEJ) repair pathway, eventually leading to accumulation of small deletions or insertions (indels) that can inactivate gene function. However, due to the variable size of the indels and the polyploid status of many cell lines (e...
May 10, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28499369/characterization-of-a-splice-site-mutation-in-the-tumor-suppressor-gene-flcn-associated-with-renal-cancer
#9
Malte P Bartram, Tripti Mishra, Nadine Reintjes, Francesca Fabretti, Hakam Gharbi, Alexander C Adam, Heike Göbel, Mareike Franke, Bernhard Schermer, Stefan Haneder, Thomas Benzing, Bodo B Beck, Roman-Ulrich Müller
BACKGROUND: Renal cell carcinoma is among the most prevalent malignancies. It is generally sporadic. However, genetic studies of rare familial forms have led to the identification of mutations in causative genes such as VHL and FLCN. Mutations in the FLCN gene are the cause of Birt-Hogg-Dubé syndrome, a rare tumor syndrome which is characterized by the combination of renal cell carcinoma, pneumothorax and skin tumors. METHODS: Using Sanger sequencing we identify a heterozygous splice-site mutation in FLCN in lymphocyte DNA of a patient suffering from renal cell carcinoma...
May 12, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28489428/a-single-molecule-view-of-genome-editing-proteins-biophysical-mechanisms-for-tales-and-crispr-cas9
#10
Luke Cuculis, Charles M Schroeder
Exciting new advances in genome engineering have unlocked the potential to radically alter the treatment of human disease. In this review, we discuss the application of single-molecule techniques to uncover the mechanisms behind two premier classes of genome editing proteins: transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system (Cas). These technologies have facilitated a striking number of gene editing applications in a variety of organisms; however, we are only beginning to understand the molecular mechanisms governing the DNA editing properties of these systems...
May 10, 2017: Annual Review of Chemical and Biomolecular Engineering
https://www.readbyqxmd.com/read/28484818/rives-technique-for-the-primary-larger-inguinal-hernia-repair-a-prospective-study-of-1000-repairs
#11
Enrique J Grau-Talens, Carlos D Ibáñez, Jacob Motos-Micó, Francisco García-Olives, Martina Arribas-Jurado, Carlos Jordán-Chaves, José M Aparicio-Gallego, José F Salgado
OBJECTIVE: We report a prospective study of repairs using the Rives technique of the more difficult primary inguinal hernias, focusing on the immediate post-operative period, clinical recurrence, testicular atrophy, and chronic pain. A mesh placed in the preperitoneal space can reduce recurrences and chronic pain. METHODS: For the larger primary inguinal hernias (Types 3, 4, 6, and some 7), we favour preperitoneal placement of a mesh, covering the myopectineal orifice by means of a transinguinal (Rives technique) approach...
May 8, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/28480303/a-one-step-pcr-based-assay-to-evaluate-the-efficiency-and-precision-of-genomic-dna-editing-tools
#12
Diego Germini, Yara Bou Saada, Tatiana Tsfasman, Kristina Osina, Chloé Robin, Nikolay Lomov, Mikhail Rubtsov, Nikolajs Sjakste, Mar Lipinski, Yegor Vassetzky
Despite rapid progress, many problems and limitations persist and limit the applicability of gene-editing techniques. Making use of meganucleases, TALENs, or CRISPR/Cas9-based tools requires an initial step of pre-screening to determine the efficiency and specificity of the designed tools. This step remains time consuming and material consuming. Here we propose a simple, cheap, reliable, time-saving, and highly sensitive method to evaluate a given gene-editing tool based on its capacity to induce chromosomal translocations when combined with a reference engineered nuclease...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28479163/cell-penetrating-peptides-cpps-from-delivery-of-nucleic-acids-and-antigens-to-transduction-of-engineered-nucleases-for-application-in-transgenesis
#13
REVIEW
Gandhi Rádis-Baptista, Iana S Campelo, Jean-Étienne R L Morlighem, Luciana M Melo, Vicente J F Freitas
Cell-penetrating peptides (CPPs) have been studied for their capacity to translocate across the lipid membrane of several cell types. In membrane translocation, these peptides can remarkably transport biologically active hydrophilic molecules, such as pharmaceuticals, nucleic acids (DNA and RNA) and even high-molecular-weight proteins, Fig. 3 into the cell cytoplasm and organelles. The development of CPPs as transduction agents includes the modification of gene and protein expression, the reprogramming and differentiation of induced pluripotent stem cells and the preparation of cellular vaccines...
May 4, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28478735/gene-therapy-of-adult-neuronal-ceroid-lipofuscinoses-with-crispr-cas9-in-zebrafish
#14
Xiaomin Yao, Xiaowei Liu, Yaguang Zhang, Yuhao Li, Chengjian Zhao, Shaohua Yao, Yu-Quan Wei
Adult-Onset Neuronal Ceroid Lipofuscinosis (ANCL), one of the neuronal ceroid lipofuscinosis (NCLs), is an inherited neurodegenerative disorder with progressive neuronal dysfunction. Recently, mutations in DNAJC5 gene that encodes Cysteine-String protein Alpha (CSPα) have been reported to be associated with familial Autosomal-Dominant ANCL (AD-ANCL). Here, we constructed an ANCL transgenic zebrafish model expressing human mutant DNAJC5 (mDNAJC5) gene under the control of a zebrafish neuron-specific promoter...
May 6, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28471514/developmental-competence-of-porcine-genome-edited-zygotes
#15
REVIEW
M A Gil, C A Martinez, A Nohalez, I Parrilla, J Roca, J Wu, P J Ross, C Cuello, J C Izpisua, E A Martinez
Genome editing in pigs has tremendous practical applications for biomedicine. The advent of genome editing technology, with its use of site-specific nucleases - including ZFNs, TALENs, and the CRISPR/Cas9 system - has popularized targeted zygote genome editing via one-step microinjection in several mammalian species. Here, we review methods to optimize the developmental competence of genome-edited porcine embryos and strategies to improve the zygote genome-editing efficiency in pigs.This article is protected by copyright...
May 4, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28465431/vimentin-fibers-orient-traction-stress
#16
Nancy Costigliola, Liya Ding, Christoph J Burckhardt, Sangyoon J Han, Edgar Gutierrez, Andressa Mota, Alex Groisman, Timothy J Mitchison, Gaudenz Danuser
The intermediate filament vimentin is required for cells to transition from the epithelial state to the mesenchymal state and migrate as single cells; however, little is known about the specific role of vimentin in the regulation of mesenchymal migration. Vimentin is known to have a significantly greater ability to resist stress without breaking in vitro compared with actin or microtubules, and also to increase cell elasticity in vivo. Therefore, we hypothesized that the presence of vimentin could support the anisotropic mechanical strain of single-cell migration...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28451378/plant-genome-editing-with-talen-and-crispr
#17
REVIEW
Aimee Malzahn, Levi Lowder, Yiping Qi
Genome editing promises giant leaps forward in advancing biotechnology, agriculture, and basic research. The process relies on the use of sequence specific nucleases (SSNs) to make DNA double stranded breaks at user defined genomic loci, which are subsequently repaired by two main DNA repair pathways: non-homologous end joining (NHEJ) and homology directed repair (HDR). NHEJ can result in frameshift mutations that often create genetic knockouts. These knockout lines are useful for functional and reverse genetic studies but also have applications in agriculture...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28448636/successful-vitrification-of-pronuclear-stage-pig-embryos-with-a-novel-cryoprotective-agent-carboxylated-%C3%AE%C2%B5-poly-l-lysine
#18
Maki Kamoshita, Tsubasa Kato, Katsuyoshi Fujiwara, Takafumi Namiki, Kazuaki Matsumura, Suong-Hyu Hyon, Junya Ito, Naomi Kashiwazaki
Vitrification is a powerful tool for the efficient production of offspring derived from cryopreserved oocytes or embryos in mammalian species including domestic animals. Genome editing technologies such as transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated (Cas)9 are now available even for domestic species, suggesting that the vitrification of embryos at the pronuclear stage (PN) will be more important because they could provide genomic host cells to be targeted by TALENs or CRISPR/Cas9...
2017: PloS One
https://www.readbyqxmd.com/read/28430356/crispr-cas9-an-rna-guided-highly-precise-synthetic-tool-for-plant-genome-editing
#19
REVIEW
Yeliz Demirci, Baohong Zhang, Turgay Unver
CRISPR/Cas 9 is a newly developed and naturally occurred genome editing tool, which is originally used by bacteria for immune defence. In the past years, it has been quickly employed and modified to precisely edit genome sequences in both plants and animals. Compared with the well-developed zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), CRISPR/Cas 9 has lots of advantages, including easier to design and implement, higher targeting efficiency, and less expensive. Thus, it is becoming one of the most powerful tools for knockout of an individual gene as well as insertion of one gene and/or control of gene transcription...
April 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28427156/the-effects-of-dleu1-gene-expression-in-burkitt-lymphoma-bl-potential-mechanism-of-chemoimmunotherapy-resistance-in-bl
#20
Sanghoon Lee, Wen Luo, Tishi Shah, Changhong Yin, Timmy O'Connell, Tae-Hoon Chung, Sherrie L Perkins, Rodney R Miles, Janet Ayello, Erin Morris, Lauren Harrison, Carmella van de Ven, Mitchell S Cairo
Following a multivariant analysis we demonstrated that children and adolescents with Burkitt lymphoma (BL) and a 13q14.3 deletion have a significant decrease in event free survival (EFS) despite identical short intensive multi-agent chemotherapy. However, how this deletion in the 13q14.3 region is associated with a significant decrease in EFS in children and adolescents with BL is largely unknown. The gene Deleted in Lymphocytic Leukemia 1 (DLEU1) is located in the region of 13q14.3. Here, we report that DLEU1 expression is implicated in the regulation of BL programmed cell death, cell proliferation, and expression of apoptotic genes in transcription activator-like effector nuclease (TALEN)s-induced DLEU1 knockdown and DLEU1 overexpressing BL cell lines...
April 25, 2017: Oncotarget
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