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"gene editing"

Shuping Yang, Xin Li, Xinfeng Liu, Xiangbin Ding, Xiangbo Xin, Congfei Jin, Sheng Zhang, Guangpeng Li, Hong Guo
MSTN -encoded myostatin is a negative regulator of skeletal muscle development. Here, we utilized the gluteus tissues from MSTN gene editing and wild type Luxi beef cattle which are native breed of cattle in China, performed tandem mass tag (TMT) -based comparative proteomics and phosphoproteomics analyses to investigate the regulatory mechanism of MSTN related to cellular metabolism and signaling pathway in muscle development. Out of 1,315 proteins, 69 differentially expressed proteins (DEPs) were found in global proteomics analysis...
February 16, 2018: Oncotarget
Jean-François Boisclair Lachance, Jemma L Webber, Lu Hong, Aaron Dinner, Ilaria Rebay
Cis -regulatory modules (CRMs) are defined by unique combinations of transcription factor-binding sites. Emerging evidence suggests that the number, affinity, and organization of sites play important roles in regulating enhancer output and, ultimately, gene expression. Here, we investigate how the cis -regulatory logic of a tissue-specific CRM responsible for even-skipped ( eve ) induction during cardiogenesis organizes the competing inputs of two E-twenty-six (ETS) members: the activator Pointed (Pnt) and the repressor Yan...
March 13, 2018: Genes & Development
Adele S Ricciardi, Elias Quijano, Rachael Putman, W Mark Saltzman, Peter M Glazer
Peptide nucleic acids (PNAs) can bind duplex DNA in a sequence-targeted manner, forming a triplex structure capable of inducing DNA repair and producing specific genome modifications. Since the first description of PNA-mediated gene editing in cell free extracts, PNAs have been used to successfully correct human disease-causing mutations in cell culture and in vivo in preclinical mouse models. Gene correction via PNAs has resulted in clinically-relevant functional protein restoration and disease improvement, with low off-target genome effects, indicating a strong therapeutic potential for PNAs in the treatment or cure of genetic disorders...
March 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Abulajiang Abudureheman, Julaiti Ainiwaer, Zhichao Hou, Madiniyat Niyaz, Abdugheni Turghun, Ayshamgul Hasim, Haiping Zhang, Xiaomei Lu, Ilyar Sheyhidin
BACKGROUND: MLL2 has been identified as one of the most frequently mutated genes in a variety of cancers including esophageal squamous cell carcinoma (ESCC). However, its clinical significance and prognostic value in ESCC has not been elucidated. In the present study, we aimed to investigate the expression and role of MLL2 in ESCC. METHODS: Immunohistochemistry (IHC) and qRT-PCR were used to examine the expression profile of MLL2. Kaplan-Meier survival analysis and univariate and multivariate Cox analyses were used to investigate the clinical and prognostic significance of MLL2 expression in Kazakh ESCC patients...
March 12, 2018: Journal of Cancer Research and Clinical Oncology
Christoph Rehmann-Sutter
Do we have a moral obligation to genetically cure embryos rather than selecting between them? Such an obligation would be an ethical argument for human germline gene editing (hGGE) to avoid the inheritance of genetic conditions instead of using pre-implantation genetic diagnosis (PGD). In this article, the intuition that we do have such a moral obligation is critically evaluated. The article first develops a theoretical framework for discussing the ethical questions of hGGE. This framework is based on an exploration of the phenomenology of the germline, from both biological and philosophical points of view...
April 2018: New Bioethics: a Multidisciplinary Journal of Biotechnology and the Body
Jessica Cussins, Leah Lowthorp
'Mitochondrial replacement' and 'germline gene editing' are relatively new techniques that represent a significant moral, technological, and legal threshold, as they would introduce permanent and heritable changes to the human gene pool. This article examines the close relationship between these two technologies over time, considering what regulatory lessons can be learned from the former as attention turns to the latter. It argues that the UK's 'mitochondrial replacement' approval process should not be taken as a model for the wider regulation of germline gene editing, and that policy-making needs to contend with a comprehensive picture of the social and political meaning of these technologies in the world...
April 2018: New Bioethics: a Multidisciplinary Journal of Biotechnology and the Body
Trevor Stammers
No abstract text is available yet for this article.
April 2018: New Bioethics: a Multidisciplinary Journal of Biotechnology and the Body
James Davison
Novel technological developments mean that gene editing - making deliberately targeted alterations in specific genes - is now a clinical reality. The inherited metabolic disorders, a group of clinically significant, monogenic disorders, provide a useful paradigm to explore some of the many ethical issues that arise from this technological capability. Fundamental questions about the significance of the genome, and of manipulating it by selection or editing, are reviewed, and a particular focus on the legislative process that has permitted the development of mitochondrial donation techniques is considered...
April 2018: New Bioethics: a Multidisciplinary Journal of Biotechnology and the Body
Zhao Dong, Haozhe Shi, Mingming Zhao, Xin Zhang, Wei Huang, Yuhui Wang, Lemin Zheng, Xunde Xian, George Liu
OBJECTIVE: Lecithin cholesterol acyltransferase (LCAT) plays a pivotal role in HDL metabolism but its influence on atherosclerosis remains controversial for decades both in animal and clinical studies. Because lack of cholesteryl ester transfer protein (CETP) is a major difference between murine and humans in lipoprotein metabolism, we aimed to create a novel Syrian Golden hamster model deficient in LCAT activity, which expresses endogenous CETP, to explore its metabolic features and particularly the influence of LCAT on the development of atherosclerosis...
March 8, 2018: Metabolism: Clinical and Experimental
Joyce C Ohiri, Elizabeth M McNally
With an increasing understanding of genetic defects leading to cardiomyopathy, focus is shifting to correcting these underlying genetic defects. One approach involves treating mutant RNA through antisense oligonucleotides; the first drug has received regulatory approval to treat specific mutations associated with Duchenne muscular dystrophy. Gene editing is being evaluated in the preclinical setting. For inherited cardiomyopathies, genetic correction strategies require tight specificity for the mutant allele...
April 2018: Heart Failure Clinics
Peng Zhang, Guannan Zhao, Liang Ji, Jinggang Yin, Lu Lu, Wei Li, Guomin Zhou, Edward Chaum, Junming Yue
Proliferative vitreoretinopathy (PVR) is a common complication of open globe injury and the most common cause of failed retinal detachment surgery. The response by retinal pigment epithelial (RPE) cells liberated into the vitreous includes proliferation and migration; most importantly, epithelial to mesenchymal transition (EMT) of RPE plays a central role in the development and progress of PVR. For the first time, we show that knockdown of BIRC5, a member of the inhibitor of apoptosis family, using either lentiviral vector based CRISPR/Cas9 nickase gene editing or inhibition of survivin using the small-molecule inhibitor YM155, results in the suppression of EMT in RPE cells...
March 6, 2018: Biochemical and Biophysical Research Communications
Karen P Maruska, Russell D Fernald
Most biomedical research is performed using a very limited number of "model" species. In part, this has resulted from a combination of full genomes, manipulation of genes, and short generation times in these species. However, the advent of low cost sequencing and gene editing in any organism has increased the use of non-traditional organisms. Many scientists have paraphrased the adage by Krogh that for many biological problems some species will prove to be most convenient and useful to study (1). In particular, using organisms most suited to the specific research question can lead to novel insights about fundamental physiological, neurobiological, immunological and neuroendocrine systems that can advance our understanding of the well-being and health of humans...
March 9, 2018: ACS Chemical Neuroscience
Harshana S De Silva Feelixge, Daniel Stone, Pavitra Roychoudhury, Martine Aubert, Keith R Jerome
Chronic viral infections remain a major public health issue affecting millions of people worldwide. Highly active antiviral treatments have significantly improved prognosis and infection-related morbidity and mortality, but have failed to eliminate persistent viral forms. Therefore, new strategies to either eradicate or control these viral reservoirs are paramount to allow patients to stop antiretroviral therapy and realize a cure. Viral genome disruption based on gene editing by programmable endonucleases is one promising curative gene therapy approach...
March 9, 2018: ACS Infectious Diseases
Harry D Dawson, Joan K Lunney
Pigs are a major source of food worldwide; preventing and treating their infectious diseases is essential, requiring a thorough understanding of porcine immunity. The use of pigs as models for human physiology is a growing area; progress in this area has been limited because the immune toolkit is not robust. The international community has established cluster of differentiation (CD) markers for assessing cells involved in immunity as well as characterizing numerous other cells like stem cells. Overall, for humans 419 proteins have been designated as CD markers, each reacting with a defined set of antibodies (Abs)...
February 22, 2018: Research in Veterinary Science
Yuemei Dong, Maria L Simões, Eric Marois, George Dimopoulos
Plasmodium relies on numerous agonists during its journey through the mosquito vector, and these agonists represent potent targets for transmission-blocking by either inhibiting or interfering with them pre- or post-transcriptionally. The recently developed CRISPR/Cas9-based genome editing tools for Anopheles mosquitoes provide new and promising opportunities for the study of agonist function and for developing malaria control strategies through gene deletion to achieve complete agonist inactivation. Here we have established a modified CRISPR/Cas9 gene editing procedure for the malaria vector Anopheles gambiae, and studied the effect of inactivating the fibrinogen-related protein 1 (FREP1) gene on the mosquito's susceptibility to Plasmodium and on mosquito fitness...
March 2018: PLoS Pathogens
Mengyuan Hao, Yanhua Cui, Xiaojun Qu
CRISPR-Cas (Clustered regularly interspaced short palindromic repeats-CRISPR associated proteins) loci, which provide a specific immunity against exogenous elements, are hypervariable among distinct prokaryotes. Based on previous researches, this review focuses on concluding systematical genome editing protocols in Streptococcus thermophilus. Firstly, its protocols and optimized conditions in gene editing are introduced. What's more, classification and diversity analyses of S. thermophilus CRISPR-Cas benefit the further understanding of evolution relationship among Streptococcus...
2018: Frontiers in Microbiology
(no author information available yet)
Kite and Sangamo signed a deal worth potentially more than $3 billion to jointly develop cellular immunotherapies using zinc finger nuclease gene-editing technologies.
March 6, 2018: Cancer Discovery
Andrew Spicer, Attila Molnar
It is abundantly clear that the development of gene editing technologies, represents a potentially powerful force for good with regard to human and animal health and addressing the challenges we continue to face in a growing global population. This now includes the development of approaches to modify microalgal strains for potential improvements in productivity, robustness, harvestability, processability, nutritional composition, and application. The rapid emergence and ongoing developments in this area demand a timely review and revision of the current definitions and regulations around genetically modified organisms (GMOs), particularly within Europe...
March 6, 2018: Biology
Mehran Makvandi, Austin Pantel, Lauren Schwartz, Erin Schubert, Kuiying Xu, Chia-Ju Hsieh, Catherine Hou, Hyoung Kim, Chi-Chang Weng, Harrison Winters, Robert Doot, Michael D Farwell, Daniel A Pryma, Roger A Greenberg, David A Mankoff, Fiona Simpkins, Robert H Mach, Lilie L Lin
BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors are effective in a broad population of ovarian cancer patients, however resistance caused by low enzyme expression of the drug target, poly(ADP-ribose) polymerase 1 (PARP-1), remains to be clinically evaluated in this context. We hypothesize that PARP-1 expression is variable in ovarian cancer and can be quantified in primary and metastatic disease using a novel positron emitting tomography (PET) imaging agent. METHODS: We used a translational approach to describe the significance of PET imaging of PARP-1 in ovarian cancer...
March 6, 2018: Journal of Clinical Investigation
Yan-Dong Tang, Jin-Chao Guo, Tong-Yun Wang, Kuan Zhao, Ji-Ting Liu, Jia-Cong Gao, Zhi-Jun Tian, Tong-Qing An, Xue-Hui Cai
Several groups have used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) for DNA virus editing. In most cases, one single-guide RNA (sgRNA) is used, which produces inconsistencies in gene editing. In this study, we used a swine herpesvirus, pseudorabies virus, as a model to systematically explore the application of CRISPR/Cas9 in DNA virus editing. In our current report, we demonstrated that cotransfection of 2 sgRNAs and a viral genome resulted in significantly better knockout efficiency than the transfection-infection-based approach...
March 6, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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