keyword
MENU ▼
Read by QxMD icon Read
search

crispr therapeutics

keyword
https://www.readbyqxmd.com/read/28220462/genome-editing-for-the-study-of-cardiovascular-diseases
#1
REVIEW
Alexandra C Chadwick, Kiran Musunuru
PURPOSE OF REVIEW: The opportunities afforded through the recent advent of genome-editing technologies have allowed investigators to more easily study a number of diseases. The advantages and limitations of the most prominent genome-editing technologies are described in this review, along with potential applications specifically focused on cardiovascular diseases. RECENT FINDINGS: The recent genome-editing tools using programmable nucleases, such as zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9), have rapidly been adapted to manipulate genes in a variety of cellular and animal models...
March 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28215705/kras-allelic-imbalance-enhances-fitness-and-modulates-map-kinase-dependence-in-cancer
#2
Michael R Burgess, Eugene Hwang, Rana Mroue, Craig M Bielski, Anica M Wandler, Benjamin J Huang, Ari J Firestone, Amy Young, Jennifer A Lacap, Lisa Crocker, Saurabh Asthana, Elizabeth M Davis, Jin Xu, Keiko Akagi, Michelle M Le Beau, Qing Li, Benjamin Haley, David Stokoe, Deepak Sampath, Barry S Taylor, Marie Evangelista, Kevin Shannon
Investigating therapeutic "outliers" that show exceptional responses to anti-cancer treatment can uncover biomarkers of drug sensitivity. We performed preclinical trials investigating primary murine acute myeloid leukemias (AMLs) generated by retroviral insertional mutagenesis in Kras(G12D) "knockin" mice with the MEK inhibitor PD0325901 (PD901). One outlier AML responded and exhibited intrinsic drug resistance at relapse. Loss of wild-type (WT) Kras enhanced the fitness of the dominant clone and rendered it sensitive to MEK inhibition...
February 16, 2017: Cell
https://www.readbyqxmd.com/read/28215090/nonviral-genome-editing-based-on-a-polymer-derivatized-crispr-nanocomplex-for-targeting-bacterial-pathogens-and-antibiotic-resistance
#3
Yoo Kyung Kang, Kyu Kwon, Jea Sung Ryu, Ha Neul Lee, Chankyu Park, Hyun Jung Chung
The overuse of antibiotics plays a major role in the emergence and spread of multidrug-resistant bacteria. A molecularly targeted, specific treatment method for bacterial pathogens can prevent this problem by reducing the selective pressure during microbial growth. Herein, we introduce a nonviral treatment strategy delivering genome editing material for targeting antibacterial resistance. We apply the CRISPR-Cas9 system, which has been recognized as an innovative tool for highly specific and efficient genome engineering in different organisms, as the delivery cargo...
February 19, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28212528/the-crispr-cas9%C3%A2-system-efficiently-reverts-the-tumorigenic-ability-of-bcr-abl-in-vitro-and-in-a-xenograft-model-of-chronic-myeloid-leukemia
#4
Ignacio García-Tuñón, María Hernández-Sánchez, José Luis Ordoñez, Veronica Alonso-Pérez, Miguel Álamo-Quijada, Rocio Benito, Carmen Guerrero, Jesús María Hernández-Rivas, Manuel Sánchez-Martín
CRISPR/Cas9 technology was used to abrogate p210 oncoprotein expression in the Boff-p210 cell line, a pro-B line derived from interlukin-3-dependent Baf/3, that shows IL-3-independence arising from the constitutive expression of BCR-ABL p210. Using this approach, pools of Boff-p210-edited cells and single edited cell-derived clones were obtained and functionally studied in vitro. The loss of p210 expression in Boff-p210 cells resulted in the loss of ability to grow in the absence of IL-3, as the Baf/3 parental line, showing significantly increased apoptosis levels...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212417/splitax-a-novel-method-to-assess-the-function-of-engineered-nucleases
#5
Richard A Axton, Sharmin S Haideri, Martha Lopez-Yrigoyen, Helen A Taylor, Lesley M Forrester
Engineered nucleases have been used to generate knockout or reporter cell lines and a range of animal models for human disease. These new technologies also hold great promise for therapeutic genome editing. Current methods to evaluate the activity of these nucleases are time consuming, require extensive optimization and are hampered by readouts with low signals and high background. We have developed a simple and easy to perform method (SplitAx) that largely addresses these issues and provides a readout of nuclease activity...
2017: PloS One
https://www.readbyqxmd.com/read/28209587/genome-surgery-using-cas9-ribonucleoproteins-for-the-treatment-of-age-related-macular-degeneration
#6
Kyoungmi Kim, Sung Wook Park, Jin Hyoung Kim, Seung Hwan Lee, Daesik Kim, Taeyoung Koo, Kwang-Eun Kim, Jeong Hun Kim, Jin-Soo Kim
RNA-guided genome surgery using CRISPR-Cas9 nucleases has shown promise for the treatment of diverse genetic diseases. Yet, the potential of such nucleases for therapeutic applications in nongenetic diseases is largely unexplored. Here, we focus on age-related macular degeneration (AMD), a leading cause of blindness in adults, which is associated with retinal overexpression of, rather than mutations in, the VEGFA gene. Subretinal injection of preassembled, Vegfa gene-specific Cas9 ribonucleoproteins (RNPs) into the adult mouse eye gave rise to mutagenesis at the target site in the retinal pigment epithelium...
February 16, 2017: Genome Research
https://www.readbyqxmd.com/read/28202911/what-rheumatologists-need-to-know-about-crispr-cas9
#7
REVIEW
Gary J Gibson, Maozhou Yang
CRISPR/Cas9 genome editing technology has taken the research world by storm since its use in eukaryotes was first proposed in 2012. Publications describing advances in technology and new applications have continued at an unrelenting pace since that time. In this Review, we discuss the application of CRISPR/Cas9 for creating gene mutations - the application that initiated the current avalanche of interest - and new developments that have largely answered initial concerns about its specificity and ability to introduce new gene sequences...
February 9, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28199983/a-versatile-system-for-rapid-multiplex-genome-edited-car-t-cell-generation
#8
Jiangtao Ren, Xuhua Zhang, Xiaojun Liu, Chongyun Fang, Shuguang Jiang, Carl H June, Yangbing Zhao
The therapeutic potential of CRISPR system has already been demonstrated in many instances and begun to overlap with the rapidly expanding field of cancer immunotherapy, especially on the production of genetically modified T cell receptor or chimeric antigen receptor (CAR) T cells. Efficient genomic disruption of multiple gene loci to generate universal donor cells, as well as potent effector T cells resistant to multiple inhibitory pathways such as PD-1 and CTLA4 is an attractive strategy for cell therapy...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28198142/therapeutic-genome-engineering-via-crispr-cas-systems
#9
REVIEW
Ana M Moreno, Prashant Mali
Differences in genomes underlie most organismal diversity, and aberrations in genomes underlie many disease states. With the growing knowledge of the genetic and pathogenic basis of human disease, development of safe and efficient platforms for genome and epigenome engineering will transform our ability to therapeutically target human diseases and also potentially engineer disease resistance. In this regard, the recent advent of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) RNA-guided nuclease systems have transformed our ability to target nucleic acids...
February 15, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28196470/proteasome-impairment-in-neural-cells-derived-from-hmsn-p-patient-ipscs
#10
Nagahisa Murakami, Keiko Imamura, Yuishin Izumi, Naohiro Egawa, Kayoko Tsukita, Takako Enami, Takuya Yamamoto, Toshitaka Kawarai, Ryuji Kaji, Haruhisa Inoue
Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is caused by a heterozygous mutation (P285L) in Tropomyosin-receptor kinase Fused Gene (TFG), histopathologically characterized by progressive spinal motor neuron loss with TFG cytosolic aggregates. Although the TFG protein, found as a type of fusion oncoprotein, is known to facilitate vesicle transport from endoplasmic reticulum (ER) to Golgi apparatus at ER exit site, it is unclear how mutant TFG causes motor neuron degeneration...
February 15, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28192788/metabolic-gatekeeper-function-of-b-lymphoid-transcription-factors
#11
Lai N Chan, Zhengshan Chen, Daniel Braas, Jae-Woong Lee, Gang Xiao, Huimin Geng, Kadriye Nehir Cosgun, Christian Hurtz, Seyedmehdi Shojaee, Valeria Cazzaniga, Hilde Schjerven, Thomas Ernst, Andreas Hochhaus, Steven M Kornblau, Marina Konopleva, Miles A Pufall, Giovanni Cazzaniga, Grace J Liu, Thomas A Milne, H Phillip Koeffler, Theodora S Ross, Isidro Sánchez-García, Arndt Borkhardt, Keith R Yamamoto, Ross A Dickins, Thomas G Graeber, Markus Müschen
B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply...
February 13, 2017: Nature
https://www.readbyqxmd.com/read/28181494/microenvironment-derived-factors-driving-metastatic-plasticity-in-melanoma
#12
Isabella S Kim, Silja Heilmann, Emily R Kansler, Yan Zhang, Milena Zimmer, Kajan Ratnakumar, Robert L Bowman, Theresa Simon-Vermot, Myles Fennell, Ralph Garippa, Liang Lu, William Lee, Travis Hollmann, Joao B Xavier, Richard M White
Cellular plasticity is a state in which cancer cells exist along a reversible phenotypic spectrum, and underlies key traits such as drug resistance and metastasis. Melanoma plasticity is linked to phenotype switching, where the microenvironment induces switches between invasive/MITF(LO) versus proliferative/MITF(HI) states. Since MITF also induces pigmentation, we hypothesize that macrometastatic success should be favoured by microenvironments that induce a MITF(HI)/differentiated/proliferative state. Zebrafish imaging demonstrates that after extravasation, melanoma cells become pigmented and enact a gene expression program of melanocyte differentiation...
February 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28178187/may-i-cut-in-gene-editing-approaches-in-human-induced-pluripotent-stem-cells
#13
REVIEW
Nicholas Brookhouser, Sreedevi Raman, Christopher Potts, David A Brafman
In the decade since Yamanaka and colleagues described methods to reprogram somatic cells into a pluripotent state, human induced pluripotent stem cells (hiPSCs) have demonstrated tremendous promise in numerous disease modeling, drug discovery, and regenerative medicine applications. More recently, the development and refinement of advanced gene transduction and editing technologies have further accelerated the potential of hiPSCs. In this review, we discuss the various gene editing technologies that are being implemented with hiPSCs...
February 6, 2017: Cells
https://www.readbyqxmd.com/read/28177825/enhancement-of-single-guide-rna-transcription-for-efficient-crispr-cas-based-genomic-engineering
#14
Kumiko Ui-Tei, Shohei Maruyama, Yuko Nakano
Genomic engineering using clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) protein is a promising approach for targeting the genomic DNA of virtually any organism in a sequence-specific manner. Recent remarkable advances in CRISPR/Cas technology have made it a feasible system for use in therapeutic applications and biotechnology. In the CRISPR/Cas system, a guide RNA (gRNA), interacting with the Cas protein, recognizes a genomic region with sequence complementarity, and the double-stranded DNA at the target site is cleaved by the Cas protein...
January 26, 2017: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28174230/crispr-cas9-coupled-affinity-purification-mass-spectrometry-analysis-revealed-a-novel-role-of-neurofibromin-in-mtor-signaling
#15
Xu Li, Min Gao, Jong Min Choi, Beom-Jun Kim, Mao-Tian Zhou, Zhen Chen, Antrix N Jain, Sung Yun Jung, Jingsong Yuan, Wenqi Wang, Yi Wang, Junjie Chen
Neurofibromin (NF1) is a well-known tumor suppressor that is commonly mutated in cancer patients. It physically interacts with RAS and negatively regulates RAS GTPase activity. Despite the importance of NF1 in cancer, a high-quality endogenous NF1 interactome has yet to be established. In this study, we combined clustered, regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated gene knockout technology with affinity purification using antibodies against endogenous proteins, followed by mass spectrometry analysis, to sensitively and accurately detect NF1 protein-protein interactions in unaltered in vivo settings...
February 7, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28170165/a-rapid-pipeline-to-model-rare-neurodevelopmental-disorders-with-simultaneous-crispr-cas9-gene-editing
#16
Scott Bell, Huashan Peng, Liam Crapper, Ilaria Kolobova, Gilles Maussion, Cristina Vasuta, Volodymyr Yerko, Tak Pan Wong, Carl Ernst
The development of targeted therapeutics for rare neurodevelopmental disorders (NDDs) faces significant challenges due to the scarcity of subjects and the difficulty of obtaining human neural cells. Here, we illustrate a rapid, simple protocol by which patient derived cells can be reprogrammed to induced pluripotent stem cells (iPSCs) using an episomal vector and differentiated into neurons. Using this platform enables patient somatic cells to be converted to physiologically active neurons in less than two months with minimal labor...
December 1, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28158191/atp6v1h-deficiency-impairs-bone-development-through-activation-of-mmp9-and-mmp13
#17
Yihan Zhang, Haigen Huang, Gexin Zhao, Tadafumi Yokoyama, Hugo Vega, Yan Huang, Raman Sood, Kevin Bishop, Valerie Maduro, John Accardi, Camilo Toro, Cornelius F Boerkoel, Karen Lyons, William A Gahl, Xiaohong Duan, May Christine V Malicdan, Shuo Lin
ATP6V1H is a component of a large protein complex with vacuolar ATPase (V-ATPase) activity. We identified two generations of individuals in which short stature and osteoporosis co-segregated with a mutation in ATP6V1H. Since V-ATPases are highly conserved between human and zebrafish, we generated loss-of-function mutants in atp6v1h in zebrafish through CRISPR/Cas9-mediated gene knockout. Homozygous mutant atp6v1h zebrafish exhibited a severe reduction in the number of mature calcified bone cells and a dramatic increase in the expression of mmp9 and mmp13...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28153089/genome-editing-reveals-glioblastoma-addiction-to-microrna-10b
#18
Rachid El Fatimy, Shruthi Subramanian, Erik J Uhlmann, Anna M Krichevsky
Glioblastoma (GBM) brain tumor remains among the most lethal and incurable human diseases. Oncogenic microRNA-10b (miR-10b) is strongly and universally upregulated in GBM, and its inhibition by antisense oligonucleotides (ASOs) reduces the growth of heterogeneous glioma cells; therefore, miR-10b represents a unique therapeutic target for GBM. Here we explored the effects of miR-10b gene editing on GBM. Using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system, we investigated effects of miR-10b gene editing on the growth of cultured human glioma cells, tumor-initiating stem-like cells, and mouse GBM xenografts, as well as the oncogene-induced transformation of normal astrocytes...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28153087/re-engineered-rna-guided-foki-nucleases-for-improved-genome-editing-in-human-cells
#19
Steven Havlicek, Yang Shen, Yunus Alpagu, Michaela B Bruntraeger, Nurdiana B M Zufir, Zhi Yi Phuah, Zhiyan Fu, Norris R Dunn, Lawrence W Stanton
Clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 enables us to generate targeted sequence changes in the genomes of cells and organisms. However, off-target effects have been a persistent problem hampering the development of therapeutics based on CRISPR/Cas9 and potentially confounding research results. Efforts to improve Cas9 specificity, like the development of RNA-guided FokI-nucleases (RFNs), usually come at the cost of editing efficiency and/or genome targetability. To overcome these limitations, we engineered improved chimeras of RFNs that enable higher cleavage efficiency and provide broader genome targetability, while retaining high fidelity for genome editing in human cells...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28148946/hiv-crispr-screen-identifies-novel-therapeutic-targets
#20
Sarah Crunkhorn
No abstract text is available yet for this article.
February 2, 2017: Nature Reviews. Drug Discovery
keyword
keyword
110211
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"