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https://www.readbyqxmd.com/read/28918562/crispr-cas9-genome-editing-in-wheat
#1
Dongjin Kim, Burcu Alptekin, Hikmet Budak
Genome editing has been a long-term challenge for molecular biology research, particularly for plants possess complex genome. The recently discovered Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system is a versatile tool for genome editing which enables editing of multiple genes based on the guidance of small RNAs. Even though the efficiency of CRISPR/Cas9 system has been shown with several studies from diploid plants, its application remains a challenge for plants with polyploid and complex genome...
September 16, 2017: Functional & Integrative Genomics
https://www.readbyqxmd.com/read/28918173/edited-course-of-biomedical-research-leaping-forward-with-crispr
#2
REVIEW
Patrick J Collins, Christopher M Hale, Han Xu
Within the short few years since the report of its application in precise genome editing, CRISPR technology has become the method of choice to modify and modulate gene expression in biomedical research and therapeutic development. Subsequently, a variety of research, diagnostic, and therapeutic tools have been developed based upon CRISPR's mechanism of action. Such tools have helped to deepen the understanding of fundamental biology and broaden the horizon in the search for treatments for diseases that have been considered hard or impossible to cure...
September 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28918164/telepsychiatry-consultation-for-medical-and-surgical-inpatient-units
#3
Julie A Graziane, Priya Gopalan, Jack Cahalane
BACKGROUND: Telepsychiatry is becoming more commonplace in the provision of psychiatric care. Most commonly used in the outpatient setting, there is little information available in the literature as to the use of telepsychiatry for inpatient medical/surgical consultation. OBJECTIVE: We review the University of Pittsburgh Medical Center's telepsychiatry consultation program that provides consultation to an outlying community-based rural hospital. METHODS: This article examines the 69 telepsychiatry consultations that were performed from November 2014 through February 2016, looking at the patients served, common consultation questions, and patterns of diagnoses and recommendations...
August 12, 2017: Psychosomatics
https://www.readbyqxmd.com/read/28918056/the-therapeutic-potential-of-crispr-cas9-systems-in-oncogene-addicted-cancer-types-virally-driven-cancers-as-a-model-system
#4
REVIEW
Luqman Jubair, Nigel A J McMillan
The field of gene editing is undergoing unprecedented growth. The first ex vivo human clinical trial in China started in 2016, more than 1000 US patents have been filed, and there is exponential growth in publications. The ability to edit genes with high fidelity is promising for the development of new treatments for a range of diseases, particularly inherited conditions, infectious diseases, and cancers. For cancer, a major issue is the identification of driver mutations and oncogenes to target for therapeutic effect, and this requires the development of robust models with which to prove their efficacy...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918053/ush2a-gene-editing-using-the-crispr-system
#5
Carla Fuster-García, Gema García-García, Elisa González-Romero, Teresa Jaijo, María D Sequedo, Carmen Ayuso, Rafael P Vázquez-Manrique, José M Millán, Elena Aller
Usher syndrome (USH) is a rare autosomal recessive disease and the most common inherited form of combined visual and hearing impairment. Up to 13 genes are associated with this disorder, with USH2A being the most prevalent, due partially to the recurrence rate of the c.2299delG mutation. Excluding hearing aids or cochlear implants for hearing impairment, there are no medical solutions available to treat USH patients. The repair of specific mutations by gene editing is, therefore, an interesting strategy that can be explored using the CRISPR/Cas9 system...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918044/targeted-disruption-of-v600e-mutant-braf-gene-by-crispr-cpf1
#6
Meijia Yang, Heng Wei, Yuelong Wang, Jiaojiao Deng, Yani Tang, Liangxue Zhou, Gang Guo, Aiping Tong
BRAF-V600E (1799T > A) is one of the most frequently reported driver mutations in multiple types of cancers, and patients with such mutations could benefit from selectively inactivating the mutant allele. Near this mutation site, there are two TTTN and one NGG protospacer-adjacent motifs (PAMs) for Cpf1 and Cas9 CRISPR nucleases, respectively. The 1799T > A substitution also leads to the occurrence of a novel NGNG PAM for the EQR variant of Cas9. We examined the editing efficacy and selectivity of Cpf1, Cas9, and EQR variant to this mutation site...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918039/crispr-cas9-mediated-knockin-application-in-cell-therapy-a-non-viral-procedure-for-bystander-treatment-of-glioma-in-mice
#7
Oscar Meca-Cortés, Marta Guerra-Rebollo, Cristina Garrido, Salvador Borrós, Nuria Rubio, Jeronimo Blanco
The use of non-viral procedures, together with CRISPR/Cas9 genome-editing technology, allows the insertion of single-copy therapeutic genes at pre-determined genomic sites, overcoming safety limitations resulting from random gene insertions of viral vectors with potential for genome damage. In this study, we demonstrate that combination of non-viral gene delivery and CRISPR/Cas9-mediated knockin via homology-directed repair can replace the use of viral vectors for the generation of genetically modified therapeutic cells...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918033/six-highly-conserved-targets-of-rnai-revealed-in-hiv-1-infected-patients-from-russia-are-also-present-in-many-hiv-1-strains-worldwide
#8
Olga V Kretova, Daria M Fedoseeva, Maria A Gorbacheva, Natalya M Gashnikova, Maria P Gashnikova, Nataliya V Melnikova, Vladimir R Chechetkin, Yuri V Kravatsky, Nickolai A Tchurikov
RNAi has been suggested for use in gene therapy of HIV/AIDS, but the main problem is that HIV-1 is highly variable and could escape attack from the small interfering RNAs (siRNAs) due to even single nucleotide substitutions in the potential targets. To exhaustively check the variability in selected RNA targets of HIV-1, we used ultra-deep sequencing of six regions of HIV-1 from the plasma of two independent cohorts of patients from Russia. Six RNAi targets were found that are invariable in 82%-97% of viruses in both cohorts and are located inside the domains specifying reverse transcriptase (RT), integrase, vpu, gp120, and p17...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918012/gene-editing-with-helper-dependent-adenovirus-can-efficiently-introduce-multiple-changes-simultaneously-over-a-large-genomic-region
#9
Donna J Palmer, Nathan C Grove, Dustin L Turner, Philip Ng
Helper-dependent adenoviral vectors (HDAds) possess long homology arms that mediate high-efficiency gene editing. These long homology arms may permit simultaneous introduction of multiple modifications into a large genomic region or may permit a single HDAd to correct many different individual mutations spread widely across a gene. We investigated this important potential using an HDAd bearing 13 genetic markers in the region of homology to the target CFTR locus in human iPSCs and found that all markers can be simultaneously introduced into the target locus, with the two farthest markers being 22...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917642/efficient-gene-editing-via-non-viral-delivery-of-crispr-cas9-system-using-polymeric-and-hybrid-microcarriers
#10
Alexander S Timin, Albert R Muslimov, Kirill V Lepik, Olga S Epifanovskaya, Alena I Shakirova, Ulrike Mock, Kristoffer Riecken, Maria V Okilova, Vladislav S Sergeev, Boris V Afanasyev, Boris Fehse, Gleb B Sukhorukov
CRISPR-Cas9 is a revolutionary genome-editing technology that has enormous potential for the treatment of genetic diseases. However, the lack of efficient and safe, non-viral delivery systems has hindered its clinical application. Here, we report on the application of polymeric and hybrid microcarriers, made of degradable polymers such as polypeptides and polysaccharides and modified by silica shell, for delivery of all CRISPR-Cas9 components. We found that these microcarriers mediate more efficient transfection than a commercially available liposome-based transfection reagent (>70% vs...
September 13, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28917584/pneumatoceles-in-pediatric-blunt-trauma-common-and-benign
#11
Lindsey B Armstrong, David P Mooney
INTRODUCTION: Traumatic pneumatoceles are reported to be rare in children and to have an uncertain clinical significance. We report a single institution series of traumatic pneumatoceles to better define their frequency and clinical significance. METHODS: After obtaining approval from the IRB, data were extracted from the trauma registry of a level 1 pediatric trauma center on children diagnosed with a pulmonary contusion (International Classification of Diseases-9th edition diagnosis codes: 861...
August 7, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28917058/lineage-tracing-of-genome-edited-alleles-reveals-high-fidelity-axolotl-limb-regeneration
#12
Grant Parker Flowers, Lucas D Sanor, Craig M Crews
Salamanders are unparalleled among tetrapods in their ability to regenerate many structures, including entire limbs, and the study of this ability may provide insights into human regenerative therapies. The complex structure of the limb poses challenges to the investigation of the cellular and molecular basis of its regeneration. Using CRISPR/Cas, we genetically labelled unique cell lineages within the developing axolotl embryo and tracked the frequency of each lineage within amputated and fully regenerated limbs...
September 16, 2017: ELife
https://www.readbyqxmd.com/read/28916985/whole-plastid-transcriptomes-reveal-abundant-rna-editing-sites-and-differential-editing-status-in-phalaenopsis-aphrodite-subsp-formosana
#13
Ting-Chieh Chen, Yu-Chang Liu, Xuewen Wang, Chi-Hsuan Wu, Chih-Hao Huang, Ching-Chun Chang
BACKGROUND: RNA editing is a process of post-transcriptional level of gene regulation by nucleotide modification. Previously, the chloroplast DNA of Taiwan endemic moth orchid, P. aphrodite subsp. formosana was determined, and 44 RNA editing sites were identified from 24 plastid protein-coding transcripts of leaf tissue via RT-PCR and then conventional Sanger sequencing. However, the RNA editing status of whole-plastid transcripts in leaf and other distinct tissue types in moth orchids has not been addressed...
September 16, 2017: Botanical Studies (Taipei, Taiwan)
https://www.readbyqxmd.com/read/28916816/striking-diflubenzuron-resistance-in-culex-pipiens-the-prime-vector-of-west-nile-virus
#14
Linda Grigoraki, Arianna Puggioli, Konstantinos Mavridis, Vassilis Douris, Mario Montanari, Romeo Bellini, John Vontas
Culex pipiens mosquitoes cause severe nuisance and transmit human diseases including West Nile. Vector control by insecticides is the main tool to prevent these diseases and diflubenzuron is one of the most effective mosquito larvicides used in many places. Here, high levels of resistance were identified in Cx. pipiens from Italy, with a Resistance Ratio of 128 fold. The phenotype was associated with mutations at amino acid I1043 (I1043M and I1043L) of the Chitin synthase gene, which showed significantly higher frequency in bioassay survivors...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916792/smartflares-fail-to-reflect-their-target-transcripts-levels
#15
Maria Czarnek, Joanna Bereta
SmartFlare probes have recently emerged as a promising tool for visualisation and quantification of specific RNAs in living cells. They are supposed to overcome the common drawbacks of current methods for RNA analysis: the need of cell fixation or lysis, or the requirements for genetic manipulations. In contrast to the traditional methods, SmartFlare probes are also presumed to provide information on RNA levels in single cells. Disappointingly, the results of our comprehensive study involving probes specific to five different transcripts, HMOX1, IL6, PTGS2, Nrg1, and ERBB4, deny the usefulness of SmartFlare probes for RNA analysis...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916764/rapid-and-reversible-epigenome-editing-by-endogenous-chromatin-regulators
#16
Simon M G Braun, Jacob G Kirkland, Emma J Chory, Dylan Husmann, Joseph P Calarco, Gerald R Crabtree
Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28916711/comparative-analysis-of-three-dimensional-chromosomal-architecture-identifies-a-novel-fetal-hemoglobin-regulatory-element
#17
Peng Huang, Cheryl A Keller, Belinda Giardine, Jeremy D Grevet, James O J Davies, Jim R Hughes, Ryo Kurita, Yukio Nakamura, Ross C Hardison, Gerd A Blobel
Chromatin structure is tightly intertwined with transcription regulation. Here we compared the chromosomal architectures of fetal and adult human erythroblasts and found that, globally, chromatin structures and compartments A/B are highly similar at both developmental stages. At a finer scale, we detected distinct folding patterns at the developmentally controlled β-globin locus. Specifically, new fetal stage-specific contacts were uncovered between a region separating the fetal (γ) and adult (δ and β) globin genes (encompassing the HBBP1 and BGLT3 noncoding genes) and two distal chromosomal sites (HS5 and 3'HS1) that flank the locus...
September 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28916446/cancer-derived-exosomes-as-a-delivery-platform-of-crispr-cas9-confer-cancer-cell-tropism-dependent-targeting
#18
Seung Min Kim, Yoosoo Yang, Seung Ja Oh, Yeonsun Hong, Mihue Jang
An intracellular delivery system for CRISPR/Cas9 is crucial for its application as a therapeutic genome editing technology in a broad range of diseases. Current vehicles carrying CRISPR/Cas9 limit in vivo delivery because of low tolerance and immunogenicity; thus, the in vivo delivery of genome editing remains challenging. Here, we report that cancer-derived exosomes function as natural carriers that can efficiently deliver CRISPR/Cas9 plasmids to cancer. Compared to epithelial cell-derived exosomes, cancer-derived exosomes provide potential vehicles for effective in vivo delivery via selective accumulation in ovarian cancer tumors of SKOV3 xenograft mice, most likely because of their cell tropism...
September 12, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28915335/ecm-related-myopathies-and-muscular-dystrophies-pros-and-cons-of-protein-therapies
#19
Pam M Van Ry, Tatiana M Fontelonga, Pamela Barraza-Flores, Apurva Sarathy, Andreia M Nunes, Dean J Burkin
Extracellular matrix (ECM) myopathies and muscular dystrophies are a group of genetic diseases caused by mutations in genes encoding proteins that provide critical links between muscle cells and the extracellular matrix. These include structural proteins of the ECM, muscle cell receptors, enzymes, and intracellular proteins. Loss of adhesion within the myomatrix results in progressive muscle weakness. For many ECM muscular dystrophies, symptoms can occur any time after birth and often result in reduced life expectancy...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28915012/managing-the-sos-response-for-enhanced-crispr-cas-based-recombineering-in-e-coli-through-transient-inhibition-of-host-reca-activity
#20
Eirik Adim Moreb, Benjamin Hoover, Adam Yaseen, Nisakorn Valyasevi, Zoe Roecker, Romel Menacho-Melgar, Michael Lynch
Phage-derived "recombineering" methods are utilized for bacterial genome editing. Recombineering results in a heterogeneous population of modified and unmodified chromosomes and therefore selection methods, such as CRISPR-Cas9, are required to select for edited clones. Cells can evade CRISPR-Cas-induced cell death through recA-mediated induction of the SOS response. The SOS response increases RecA dependent repair as well mutation rates through the induction of the umuDC error prone polymerase. As a result, CRISPR-Cas selection is more efficient in recA mutants...
September 15, 2017: ACS Synthetic Biology
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