keyword
MENU ▼
Read by QxMD icon Read
search

CRISPR CAS9 human

keyword
https://www.readbyqxmd.com/read/29238045/ripk3-promotes-adenovirus-type-5-activity
#1
Melanie Weigert, Alex Binks, Suzanne Dowson, Elaine Y L Leung, Dmitris Athineos, Xinzi Yu, Margaret Mullin, Josephine B Walton, Clare Orange, Darren Ennis, Karen Blyth, Stephen W G Tait, Iain A McNeish
Oncolytic adenoviral mutants infect human malignant cells and replicate selectively within them. This induces direct cytotoxicity that can also trigger profound innate and adaptive immune responses. However, the mechanism by which adenoviruses produce cell death remains uncertain. We previously suggested that type 5 adenoviruses, including the E1A CR2 deletion mutant dl922-947, might induce a novel form of programmed death resembling necroptosis. Here we have investigated the roles of core necrosis proteins RIPK1, RIPK3 and MLKL in the cytotoxicity of dl922-947 and other adenovirus serotypes...
December 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29237052/multimode-drug-inducible-crispr-cas9-devices-for-transcriptional-activation-and-genome-editing
#2
Jia Lu, Chen Zhao, Yingze Zhao, Jingfang Zhang, Yue Zhang, Li Chen, Qiyuan Han, Yue Ying, Shuai Peng, Runna Ai, Yu Wang
Precise investigation and manipulation of dynamic biological processes often requires molecular modulation in a controlled inducible manner. The clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) has emerged as a versatile tool for targeted gene editing and transcriptional programming. Here, we designed and vigorously optimized a series of Hybrid drug Inducible CRISPR/Cas9 Technologies (HIT) for transcriptional activation by grafting a mutated human estrogen receptor (ERT2) to multiple CRISPR/Cas9 systems, which renders them 4-hydroxytamoxifen (4-OHT) inducible for the access of genome...
December 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29234093/crispr-cas9-microinjection-in-oocytes-disables-pancreas-development-in-sheep
#3
Marcela Vilarino, Sheikh Tamir Rashid, Fabian Patrik Suchy, Bret Roberts McNabb, Talitha van der Meulen, Eli J Fine, Syed Ahsan, Nurlybek Mursaliyev, Vittorio Sebastiano, Santiago Sain Diab, Mark O Huising, Hiromitsu Nakauchi, Pablo J Ross
One of the ultimate goals of regenerative medicine is the generation of patient-specific organs from pluripotent stem cells (PSCs). Sheep are potential hosts for growing human organs through the technique of blastocyst complementation. We report here the creation of pancreatogenesis-disabled sheep by oocyte microinjection of CRISPR/Cas9 targeting PDX1, a critical gene for pancreas development. We compared the efficiency of target mutations after microinjecting the CRISPR/Cas9 system in metaphase II (MII) oocytes and zygote stage embryos...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233979/extracellular-vesicles-from-human-induced-pluripotent-stem-cell-derived-mesenchymal-stromal-cells-hipsc-mscs-protect-against-renal-ischemia-reperfusion-injury-via-delivering-specificity-protein-sp1-and-transcriptional-activating-of-sphingosine-kinase-1-and
#4
Xiaodong Yuan, Dawei Li, Xiaosong Chen, Conghui Han, Longmei Xu, Tao Huang, Zhen Dong, Ming Zhang
Renal ischemia-reperfusion is a main cause of acute kidney injury (AKI), which is associated with high mortality. Here we show that extracellular vesicles (EVs) secreted from hiPSC-MSCs play a critical role in protection against renal I/R injury. hiPSC-MSCs-EVs can fuse with renal cells and deliver SP1 into target cells, subsequently active SK1 expression and increase S1P formation. Chromatin immunoprecipitation (ChIP) analyses and luciferase assay were used to confirm SP1 binds directly to the SK1 promoter region and promote promoter activity...
December 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29229993/therapeutic-relevance-of-the-pp2a-b55-inhibitory-kinase-mastl-greatwall-in-breast-cancer
#5
Mónica Álvarez-Fernández, María Sanz-Flores, Belén Sanz-Castillo, María Salazar-Roa, David Partida, Elisabet Zapatero-Solana, H Raza Ali, Eusebio Manchado, Scott Lowe, Todd VanArsdale, David Shields, Carlos Caldas, Miguel Quintela-Fandino, Marcos Malumbres
PP2A is a major tumor suppressor whose inactivation is frequently found in a wide spectrum of human tumors. In particular, deletion or epigenetic silencing of genes encoding the B55 family of PP2A regulatory subunits is a common feature of breast cancer cells. A key player in the regulation of PP2A/B55 phosphatase complexes is the cell cycle kinase MASTL (also known as Greatwall). During cell division, inhibition of PP2A-B55 by MASTL is required to maintain the mitotic state, whereas inactivation of MASTL and PP2A reactivation is required for mitotic exit...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29229813/human-genetic-variation-alters-crispr-cas9-on-and-off-targeting-specificity-at-therapeutically-implicated-loci
#6
Samuel Lessard, Laurent Francioli, Jessica Alfoldi, Jean-Claude Tardif, Patrick T Ellinor, Daniel G MacArthur, Guillaume Lettre, Stuart H Orkin, Matthew C Canver
The CRISPR-Cas9 nuclease system holds enormous potential for therapeutic genome editing of a wide spectrum of diseases. Large efforts have been made to further understanding of on- and off-target activity to assist the design of CRISPR-based therapies with optimized efficacy and safety. However, current efforts have largely focused on the reference genome or the genome of cell lines to evaluate guide RNA (gRNA) efficiency, safety, and toxicity. Here, we examine the effect of human genetic variation on both on- and off-target specificity...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29228209/cd38-knockout-suppresses-tumorigenesis-in-mice-and-clonogenic-growth-of-human-lung-cancer-cells
#7
Xiangning Bu, Jiro Kato, Julie A Hong, Maria J Merino, David S Schrump, Frances E Lund, Joel Moss
The ectodomain of the plasma membrane ecto-enzyme CD38 functions as both an NAD glycohydrolase and an ADP-ribosyl cyclase by catalyzing, respectively, the conversion of NAD to nicotinamide and ADP-ribose or cyclic ADP-ribose. CD38 is attracting particular attention in cancer therapy. An anti-CD38 monoclonal antibody (daratumumab) was approved for treatment of patients with multiple myeloma. However, the role of CD38 in non-hematological malignancies has not been explored. Previously, we reported that ADP-ribose-acceptor hydrolase (ARH)-1 deficiency in mice was associated with tumor development...
December 8, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29225130/on-the-g-protein-coupling-selectivity-of-the-native-a2b-adenosine-receptor
#8
Zhan-Guo Gao, Asuka Inoue, Kenneth A Jacobson
A2B adenosine receptor (A2BAR) activation induces Gs-dependent cyclic AMP accumulation. However, A2BAR G protein-coupling to other signaling events, e.g. ERK1/2 and calcium, is not well documented. We explored Gi, Gq/11 and Gs coupling in 1321N1 astrocytoma, HEK293, and T24 bladder cancer cells endogenously expressing human A2BAR, using NECA or nonnucleoside BAY60-6583 as agonist, selective Gi, Gs and Gq/11 blockers, and CRISPR/Cas9-based Gq- and Gs-null HEK293 cells. In HEK293 cells, A2BAR-mediated ERK1/2 activity occurred via both Gi and Gs, but not Gq/11...
December 7, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29224783/in%C3%A2-vivo-target-gene-activation-via-crispr-cas9-mediated-trans-epigenetic-modulation
#9
Hsin-Kai Liao, Fumiyuki Hatanaka, Toshikazu Araoka, Pradeep Reddy, Min-Zu Wu, Yinghui Sui, Takayoshi Yamauchi, Masahiro Sakurai, David D O'Keefe, Estrella Núñez-Delicado, Pedro Guillen, Josep M Campistol, Cheng-Jang Wu, Li-Fan Lu, Concepcion Rodriguez Esteban, Juan Carlos Izpisua Belmonte
Current genome-editing systems generally rely on inducing DNA double-strand breaks (DSBs). This may limit their utility in clinical therapies, as unwanted mutations caused by DSBs can have deleterious effects. CRISPR/Cas9 system has recently been repurposed to enable target gene activation, allowing regulation of endogenous gene expression without creating DSBs. However, in vivo implementation of this gain-of-function system has proven difficult. Here, we report a robust system for in vivo activation of endogenous target genes through trans-epigenetic remodeling...
November 30, 2017: Cell
https://www.readbyqxmd.com/read/29223949/-will-the-crispr-cas9-system-change-the-genome-of-humanity
#10
EDITORIAL
Damasia Becú-Villalobos
No abstract text is available yet for this article.
2017: Medicina
https://www.readbyqxmd.com/read/29221193/steroidogenic-factor-1-hypermethylation-in-maternal-rat-blood-could-serve-as-a-biomarker-for-intrauterine-growth-retardation
#11
Dong-Mei Wu, Liang-Peng Ma, Gui-Li Song, Yong Long, Han-Xiao Liu, Yang Liu, Jie Ping
Intrauterine growth retardation (IUGR) is a common obstetric complication lacking an optimal method for prenatal screening. DNA methylation profile in maternal blood holds significant promise for prenatal screening. Here, we aimed to screen out potential IUGR biomarkers in maternal blood from the perspective of DNA methylation. The IUGR rat model was established by prenatal maternal undernutrition. High-throughput bisulfite sequencing of genomic DNA methylation followed by functional clustering analysis for differentially methylated region (DMR)-associated genes demonstrated that genes regulating transcription had the most significantly changed DNA methylation status in maternal blood with IUGR...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221169/targeting-pp2a-activates-ampk-signaling-to-inhibit-colorectal-cancer-cells
#12
Cuiping Dai, Xuning Zhang, Da Xie, Peipei Tang, Chunmei Li, Yi Zuo, Baofei Jiang, Caiping Xue
LB-100 is a novel PP2A inhibitor. Its activity in human colorectal cancer (CRC) cells was tested. The in vitro studies demonstrated that LB-100 inhibited survival and proliferation of both established CRC cells (HCT-116 and HT-29 lines) and primary human colon cancer cells. Further, LB-100 activated apoptosis and induced G1-S cell cycle arrest in CRC cells. LB-100 inhibited PP2A activity and activated AMPK signaling in CRC cells. AMPKα1 dominant negative mutation, shRNA-mediated knockdown or complete knockout (by CRISPR/Cas9 method) largely attenuated LB-100-induced AMPK activation and HCT-116 cytotoxicity...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29219081/whole-genome-analysis-of-crispr-cas9-sgrna-off-target-homologies-via-an-efficient-computational-algorithm
#13
Hong Zhou, Michael Zhou, Daisy Li, Joseph Manthey, Ekaterina Lioutikova, Hong Wang, Xiao Zeng
BACKGROUND: The beauty and power of the genome editing mechanism, CRISPR Cas9 endonuclease system, lies in the fact that it is RNA-programmable such that Cas9 can be guided to any genomic loci complementary to a 20-nt RNA, single guide RNA (sgRNA), to cleave double stranded DNA, allowing the introduction of wanted mutations. Unfortunately, it has been reported repeatedly that the sgRNA can also guide Cas9 to off-target sites where the DNA sequence is homologous to sgRNA. RESULTS: Using human genome and Streptococcus pyogenes Cas9 (SpCas9) as an example, this article mathematically analyzed the probabilities of off-target homologies of sgRNAs and discovered that for large genome size such as human genome, potential off-target homologies are inevitable for sgRNA selection...
November 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29218308/opportunities-for-crispr-cas9-gene-editing-in-retinal-regeneration-research
#14
REVIEW
Leah J Campbell, David R Hyde
While retinal degeneration and disease results in permanent damage and vision loss in humans, the severely damaged zebrafish retina has a high capacity to regenerate lost neurons and restore visual behaviors. Advancements in understanding the molecular and cellular basis of this regeneration response give hope that strategies and therapeutics may be developed to restore sight to blind and visually-impaired individuals. Our current understanding has been facilitated by the amenability of zebrafish to molecular tools, imaging techniques, and forward and reverse genetic approaches...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29217433/hypertrophic-cardiomyopathy-linked-mutation-in-troponin-t-causes-myofibrillar-disarray-and-pro-arrhythmic-action-potential-changes-in-human-ipsc-cardiomyocytes
#15
Lili Wang, Kyungsoo Kim, Shan Parikh, Adrian Gabriel Cadar, Kevin R Bersell, Huan He, Jose R Pinto, Dmytro O Kryshtal, Bjorn C Knollmann
BACKGROUND: Mutations in cardiac troponin T (TnT) are linked to increased risk of ventricular arrhythmia and sudden death despite causing little to no cardiac hypertrophy. Studies in mice suggest that the hypertrophic cardiomyopathy (HCM)-associated TnT-I79N mutation increases myofilament Ca sensitivity and is arrhythmogenic, but whether findings from mice translate to human cardiomyocyte electrophysiology is not known. OBJECTIVES: To study the effects of the TnT-I79N mutation in human cardiomyocytes...
December 4, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29215041/crispr-cas9-delivery-with-one-single-adenoviral-vector-devoid-of-all-viral-genes
#16
Eric Ehrke-Schulz, Maren Schiwon, Theo Leitner, Stephan Dávid, Thorsten Bergmann, Jing Liu, Anja Ehrhardt
The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system revolutionized the field of gene editing but viral delivery of the CRISPR/Cas9 system has not been fully explored. Here we adapted clinically relevant high-capacity adenoviral vectors (HCAdV) devoid of all viral genes for the delivery of the CRISPR/Cas9 machinery using a single viral vector. We present a platform enabling fast transfer of the Cas9 gene and gRNA expression units into the HCAdV genome including the option to choose between constitutive or inducible Cas9 expression and gRNA multiplexing...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29213273/targeting-trim5%C3%AE-in-hiv-cure-strategies-for-the-crispr-cas9-era
#17
Daryl Anne Victoria Weatherley, Michael Terence Boswell, Sarah L Rowland-Jones
In the past decade, studies of innate immune activity against HIV-1 and other retroviruses have revealed a powerful array of host factors that can attack the virus at various stages of its life cycle in human and primate cells, raising the prospect that these antiviral factors could be manipulated in immunotherapeutic strategies for HIV infection. This has not proved straightforward: while HIV accessory genes encode proteins that subvert or destroy many of these restriction factors, others, such as human TRIM5α show limited potency against HIV-1...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29211708/selective-silencing-of-euchromatic-l1s-revealed-by-genome-wide-screens-for-l1-regulators
#18
Nian Liu, Cameron H Lee, Tomek Swigut, Edward Grow, Bo Gu, Michael Bassik, Joanna Wysocka
Transposable elements (TEs) are now recognized not only as parasitic DNA, whose spread in the genome must be controlled by the host, but also as major players in genome evolution and regulation1-6. Long INterspersed Element-1 (LINE-1 or L1), the only currently autonomous mobile transposon in humans, occupies 17% of the genome and continues to generate inter- and intra-individual genetic variation, in some cases resulting in disease1-7. Nonetheless, how L1 activity is controlled and what function L1s play in host gene regulation remain incompletely understood...
December 6, 2017: Nature
https://www.readbyqxmd.com/read/29210109/xenotransplantation-back-to-the-future
#19
REVIEW
Raphael P H Meier, Yannick D Muller, Alexandre Balaphas, Philippe Morel, Manuel Pascual, Jörg D Seebach, Leo H Buhler
The field of xenotransplantation has fluctuated between great optimism and doubts over the last 50 years. The initial clinical attempts were extremely ambitious but faced technical and ethical issues that prompted the research community to go back to preclinical studies. Important players left the field due to perceived xenozoonotic risks and the lack of progress in pig-to-non-human-primate transplant models. Initial apparently unsurmountable issues appear now to be possible to overcome due to progress of genetic engineering, allowing the generation of multiple-xenoantigen knockout pigs that express human transgenes and the genome-wide inactivation of porcine endogenous retroviruses...
December 5, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/29209043/crispr-cas9-edited-nsg-mice-as-pdx-models-of-human-leukemia-to-address-the-role-of-niche-derived-sparc
#20
I Tirado-Gonzalez, E Czlonka, A Nevmerzhitskaya, D Soetopo, E Bergonzani, A Mahmoud, A Contreras, I Jeremias, U Platzbecker, J P Bourquin, U Kloz, F Van der Hoeven, H Medyouf
Leukemia accepted article preview online, 06 December 2017. doi:10.1038/leu.2017.346.
December 6, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
keyword
keyword
71946
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"