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Adeno-associated virus

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https://www.readbyqxmd.com/read/30540563/sevoflurane-impairs-learning-and-memory-of-the-developing-brain-through-post-transcriptional-inhibition-of-ccna2-via-microrna-19-3p
#1
Xin Zhao, Yanwu Jin, Haibo Li, Yuxiu Jia, Yuelan Wang
The molecular mechanisms underlying sevoflurane (SEVO)-induced impairment of learning and memory remain unclear. Specifically, a role of microRNAs (miRNAs) in the control of the neuron proliferation in the developing brain exposed to SEVO has not been reported previously. Here, we studied the effects of SEVO exposure on the neural cell proliferation, and on the learning and memory of neonatal rats. We found that SEVO exposure significantly decreased neuron cell proliferation, reduced BDNF levels in brain, and impaired learning and memory of neonatal rats in Morris water maze test and Plus-Maze discriminative avoidance task (PM-DAT), likely through downregulation of CCNA2 protein...
December 12, 2018: Aging
https://www.readbyqxmd.com/read/30536340/effect-of-mir-21-tlr4-nf-%C3%AE%C2%BAb-pathway-on-myocardial-apoptosis-in-rats-with-myocardial-ischemia-reperfusion
#2
Y-Q Pan, J Li, X-W Li, Y-C Li, J Li, J-F Lin
OBJECTIVE: The aim of the study was to investigate the influences of micro ribonucleic acid (miR)-21 and downstream Toll-like receptor 4 (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway on myocardial apoptosis induced by myocardial ischemia-reperfusion (I/R) injury in rats. MATERIALS AND METHODS: Recombinant adeno-associated virus rAAV9-ZsGreen-pre-miR-21 and blank control virus were constructed. A total of 48 Sprague-Dawley (SD) rats were randomly divided into S1 group (open chest only), S2 group (transfection with blank virus + open chest), I/R1 group (transfection with blank virus + 6 d of myocardial I/R), and I/R2 group (transfection with miR-21 + 6 d of myocardial I/R)...
November 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/30536073/upregulation-of-ubap2l-in-bone-marrow-mesenchymal-stem-cells-promotes-functional-recovery-in-rats-with-spinal-cord-injury
#3
Guan-Lin Lin, Huan Wang, Jun Dai, Xiao Li, Ming Guan, Qing Ding, Huai-Xi Wang, Huang Fang
Post-translational modifications of cellular proteins with ubiquitin or ubiquitin-like proteins regulate many cellular processes, such as cell proliferation, differentiation, apoptosis, signal transduction, intercellular immune recognition, inflammatory response, stress response, and DNA repair. Nice4/UBAP2L is an important member in the family of ubiquitin-like proteins, and its biological function remains unknown. This study aimed to investigate the effect of UBAP2L on spinal cord injury (SCI). At first, rat bone marrow mesenchymal stem cells (BMSCs) were infected with adeno-associated virus to induce over-expression of Nice4...
December 2018: Current medical science
https://www.readbyqxmd.com/read/30534580/codon-optimization-of-wild-type-adeno-associated-virus-capsid-sequences-enhances-dna-family-shuffling-while-conserving-functionality
#4
Marti Cabanes-Creus, Samantha L Ginn, Anais K Amaya, Sophia H Y Liao, Adrian Westhaus, Claus V Hallwirth, Patrick Wilmott, Jason Ward, Kimberley L Dilworth, Giorgia Santilli, Arkadiusz Rybicki, Hiroyuki Nakai, Adrian J Thrasher, Adrian C Filip, Ian E Alexander, Leszek Lisowski
Adeno-associated virus (AAV) vectors have become one of the most widely used gene transfer tools in human gene therapy. Considerable effort is currently being focused on AAV capsid engineering strategies with the aim of developing novel variants with enhanced tropism for specific human cell types, decreased human seroreactivity, and increased manufacturability. Selection strategies based on directed evolution rely on the generation of highly variable AAV capsid libraries using methods such as DNA-family shuffling, a technique reliant on stretches of high DNA sequence identity between input parental capsid sequences...
March 15, 2019: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/30534578/efficacy-of-a-bicistronic-vector-for-correction-of-sandhoff-disease-in-a-mouse-model
#5
Evan Woodley, Karlaina J L Osmon, Patrick Thompson, Christopher Richmond, Zhilin Chen, Steven J Gray, Jagdeep S Walia
GM2 gangliosidoses are a family of severe neurodegenerative disorders resulting from a deficiency in the β-hexosaminidase A enzyme. These disorders include Tay-Sachs disease and Sandhoff disease, caused by mutations in the HEXA gene and HEXB gene, respectively. The HEXA and HEXB genes are required to produce the α and β subunits of the β-hexosaminidase A enzyme, respectively. Using a Sandhoff disease mouse model, we tested for the first time the potential of a comparatively lower dose (2.04 × 1013 vg/kg) of systemically delivered single-stranded adeno-associated virus 9 expressing both human HEXB and human HEXA cDNA under the control of a single promoter with a P2A-linked bicistronic vector design to correct the neurological phenotype...
March 15, 2019: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/30534060/structural-connectivity-of-the-anterior-cingulate-cortex-claustrum-and-the-anterior-insula-of-the-mouse
#6
Houman Qadir, Samuel R Krimmel, Chaoqi Mu, Alexandros Poulopoulos, David A Seminowicz, Brian N Mathur
The claustrum is a narrow subcortical brain structure that resides between the striatum and insular cortex. The function of the claustrum is not fully described, and while our previous work supports a role for the claustrum in top-down cognitive control of action, other evidence suggests the claustrum may be involved in detecting salient changes in the external environment. The anterior cingulate cortex (ACC) and the anterior insular (aINS) are the two major participants in the salience network of human brain regions that activate in response to salient stimuli...
2018: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/30533449/highly-efficient-ultracentrifugation-free-chromatographic-purification-of-recombinant-aav-serotype-9
#7
Taro Tomono, Yukihiko Hirai, Hironori Okada, Yoshitaka Miyagawa, Kumi Adachi, Shuhei Sakamoto, Yasuhiro Kawano, Hideto Chono, Junichi Mineno, Akiko Ishii, Takashi Shimada, Masafumi Onodera, Akira Tamaoka, Takashi Okada
Recombinant adeno-associated virus serotype 9 (rAAV9) can specifically transduce muscle and neuronal tissues; thus, rAAV9 can potentially be used in gene therapy. However, rAAV9 is the most challenging rAAV serotype to purify. Traditionally, rAAV9 has been purified by ultracentrifugation, which is not scalable. We recently described a chromatographic purification protocol for rAAV1; this protocol can achieve scalable purifications. In this study, we attempted to optimize this protocol for purifying rAAV9 preparations, and we developed a novel, effective method for high-yield purification of rAAV9 using quaternary ammonium anion exchangers and size-exclusion chromatography...
December 14, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/30532004/impaired-anandamide-palmitoylethanolamide-signaling-in-hippocampal-glutamatergic-neurons-alters-synaptic-plasticity-learning-and-emotional-responses
#8
Tina Zimmermann, Julia C Bartsch, Annika Beer, Ermelinda Lomazzo, Stephan Guggenhuber, Maren D Lange, Laura Bindila, Hans-Christian Pape, Beat Lutz
Endocannabinoid signaling via anandamide (AEA) is implicated in a variety of neuronal functions and considered a promising therapeutic target for numerous emotion-related disorders. The major AEA degrading enzyme is fatty acid amide hydrolase (FAAH). Genetic deletion and pharmacological inhibition of FAAH reduce anxiety and improve emotional responses and memory in rodents and humans. Complementarily, the mechanisms and impact of decreased AEA signaling remain to be delineated in detail. In the present study, using the Cre/loxP system combined with an adeno-associated virus (AAV)-mediated delivery system, FAAH was selectively overexpressed in hippocampal CA1-CA3 glutamatergic neurons of adult mice...
November 15, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/30531861/cyclin-a2-e1-activation-defines-a-hepatocellular-carcinoma-subclass-with-a-rearrangement-signature-of-replication-stress
#9
Quentin Bayard, Léa Meunier, Camille Peneau, Victor Renault, Jayendra Shinde, Jean-Charles Nault, Iadh Mami, Gabrielle Couchy, Giuliana Amaddeo, Emmanuel Tubacher, Delphine Bacq, Vincent Meyer, Tiziana La Bella, Audrey Debaillon-Vesque, Paulette Bioulac-Sage, Olivier Seror, Jean-Frédéric Blanc, Julien Calderaro, Jean-François Deleuze, Sandrine Imbeaud, Jessica Zucman-Rossi, Eric Letouzé
Cyclins A2 and E1 regulate the cell cycle by promoting S phase entry and progression. Here, we identify a hepatocellular carcinoma (HCC) subgroup exhibiting cyclin activation through various mechanisms including hepatitis B virus (HBV) and adeno-associated virus type 2 (AAV2) insertions, enhancer hijacking and recurrent CCNA2 fusions. Cyclin A2 or E1 alterations define a homogenous entity of aggressive HCC, mostly developed in non-cirrhotic patients, characterized by a transcriptional activation of E2F and ATR pathways and a high frequency of RB1 and PTEN inactivation...
December 7, 2018: Nature Communications
https://www.readbyqxmd.com/read/30528929/preclinical-evaluation-of-advm-022-a-novel-gene-therapy-approach-to-treating-wet-age-related-macular-degeneration
#10
Ruslan Grishanin, Brian Vuillemenot, Pallavi Sharma, Annahita Keravala, Judith Greengard, Claire Gelfman, Mark Blumenkrantz, Matthew Lawrence, Wenzheng Hu, Szilárd Kiss, Mehdi Gasmi
Inhibition of vascular endothelial growth factor, a key contributor to the choroidal neovascularization associated with wet age-related macular degeneration, is the mode of action of several approved therapies, including aflibercept, which requires frequent intravitreal injections to provide clinical benefit. Lack of compliance with the dosing schedule may result in recurrence of active wet macular degeneration, leading to irreversible vision impairment. Gene therapy providing sustained anti-vascular endothelial growth factor levels in the retina following a single injection could drastically reduce the treatment burden and improve visual outcomes...
November 13, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/30528454/the-browning-of-white-adipose-tissue-and-body-weight-loss-in-primary-hyperparathyroidism
#11
Yang He, Rui-Xin Liu, Min-Ting Zhu, Wen-Bin Shen, Jing Xie, Zhi-Yin Zhang, Na Chen, Chang Shan, Xing-Zhi Guo, Yi-de Lu, Bei Tao, Li-Hao Sun, Hong-Yan Zhao, Rui Guo, Biao Li, Si-Min Liu, Guang Ning, Ji-Qiu Wang, Jian-Min Liu
BACKGROUND: Parathyroid hormone related protein (PTHrP) triggers white adipose tissue (WAT) browning and cachexia in lung cancer mouse models. It remains unknown whether excessive PTH secretion affects WAT browning and to what extent it contributes to body weight change in primary hyperparathyroidism (PHPT). METHODS: Using the adeno-associated virus injection, Pth gene over-expressed mice mimicking PHPT were firstly established to observe their WAT browning and body weight alteration...
December 6, 2018: EBioMedicine
https://www.readbyqxmd.com/read/30527757/mir-212-132-cluster-modulation-prevents-doxorubicin-mediated-atrophy-and-cardiotoxicity
#12
Shashi Kumar Gupta, Ankita Garg, Petros Avramopoulos, Stefan Engelhardt, Katrin Streckfuss-Bömeke, Sandor Batkai, Thomas Thum
Improved therapy of cancer has significantly increased the lifespan of patients. However, cancer survivors face an increased risk of cardiovascular complications due to adverse effects of cancer therapies. The chemotherapy drug doxorubicin is well known to induce myofibril damage and cardiac atrophy. Our aim was to test potential counteracting effects of the pro-hypertrophic miR-212/132 family in doxorubicin-induced cardiotoxicity. In vitro, overexpression of the pro-hypertrophic miR-212/132 cluster in primary rodent and human iPSC-derived cardiomyocytes inhibited doxorubicin-induced toxicity...
November 13, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/30526118/pretreatment-of-raav-mediated-expression-of-myostatin-propeptide-lowers-type-2-diabetes-incidence-in-c57bl-6-mice-on-high-fat-diet
#13
Hui Yan, Jiejie Meng, Shasha Zhang, Hang Zhuang, YuE Song, Xiao Xiao, Dao Wen Wang, Jiangang Jiang
Myostatin, a negative modulator of muscle growth, has been considered as a potential target for treatment of type 2 diabetes. In our previous work, we found that myostatin inhibition by adeno-associated virus (AAV) mediated gene delivery of myostatin propeptide (MPRO) could improve muscle mass and achieve therapeutic effects on glucose regulation and lipid metabolism in db/db mice. In this study, we investigated whether pre-intervention of rAAV-mediated expression of MPRO could lower the incidence of type 2 diabetes...
December 10, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/30524313/new-approaches-to-tay-sachs-disease-therapy
#14
REVIEW
Valeriya V Solovyeva, Alisa A Shaimardanova, Daria S Chulpanova, Kristina V Kitaeva, Lisa Chakrabarti, Albert A Rizvanov
Tay-Sachs disease belongs to the group of autosomal-recessive lysosomal storage metabolic disorders. This disease is caused by β-hexosaminidase A (HexA) enzyme deficiency due to various mutations in α-subunit gene of this enzyme, resulting in GM2 ganglioside accumulation predominantly in lysosomes of nerve cells. Tay-Sachs disease is characterized by acute neurodegeneration preceded by activated microglia expansion, macrophage and astrocyte activation along with inflammatory mediator production. In most cases, the disease manifests itself during infancy, the "infantile form," which characterizes the most severe disorders of the nervous system...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/30517201/vectored-delivery-of-anti-siv-envelope-targeting-mab-via-aav8-protects-rhesus-macaques-from-repeated-limiting-dose-intrarectal-swarm-sivsme660-challenge
#15
Hugh C Welles, Madeleine F Jennewein, Rosemarie D Mason, Sandeep Narpala, Lingshu Wang, Cheng Cheng, Yi Zhang, John-Paul Todd, Jeffrey D Lifson, Alejandro B Balazs, Galit Alter, Adrian B McDermott, John R Mascola, Mario Roederer
Gene based delivery of immunoglobulins promises to safely and durably provide protective immunity to individuals at risk of acquiring infectious diseases such as HIV. We used a rhesus macaque animal model to optimize delivery of naturally-arising, autologous anti-SIV neutralizing antibodies expressed by Adeno-Associated Virus 8 (AAV8) vectors. Vectored transgene expression was confirmed by quantitation of target antibody abundance in serum and mucosal surfaces. We tested the expression achieved at varying doses and numbers of injections...
December 5, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/30516406/overexpression-of-lh3-reduces-the-incidence-of-hypertensive-intracerebral-hemorrhage-in-mice
#16
Hao Li, Haochen Xu, Hongyan Wen, Tianlong Liu, Yingying Sun, Ning Xiao, Congxia Bai, Jing Ge, Xuliang Wang, Li Song, Yan Song, Yinhui Zhang, Jingzhou Chen
Hypertensive intracerebral hemorrhage (ICH) is a devastating cerebrovascular disease with no effective treatment. Lysyl hydroxylase 3 (LH3) is essential for collagen IV intermolecular crosslinking and stabilization. Deficiency in LH3 affects the assembly and secretion of collagen IV and basement membrane (BM) integrity of vessels. Here, we investigated whether LH3 has significant implications for disease progression and therapeutic intervention. Spontaneous hypertensive ICH of mice was induced by angiotensin II and L-NAME treatment...
December 5, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/30514969/immunosuppression-overcomes-insulin-and-vector-specific-immune-responses-that-limit-efficacy-of-aav2-8-mediated-insulin-gene-therapy-in-nod-mice
#17
Asha Recino, Shu Uin Gan, Kian Chuan Sia, Yvonne Sawyer, Jenny Trendell, Richard Kay, Fiona M Gribble, Frank Reimann, Rob Foale, Maria Notaridou, Nick Holmes, Andrew Lever, Kok Onn Lee, Amit Nathwani, Anne Cooke, Roy Calne, Maja Wallberg
We report the restoration of euglycaemia in chemically induced diabetic C57BL/6 mice and spontaneously diabetic Non Obese Diabetic (NOD) mice by intravenous systemic administration of a single-stranded adeno-associated virus (ssAAV2/8) codon optimised (co) vector encoding furin cleavable human proinsulin under a liver-specific promoter. There were no immunological barriers to efficacy of insulin gene therapy in chemically induced C57BL/6 mice, which enjoyed long-lasting correction of hyperglycaemia after therapy, up to 250 days...
December 4, 2018: Gene Therapy
https://www.readbyqxmd.com/read/30514868/pathway-sensor-based-functional-genomics-screening-identifies-modulators-of-neuronal-activity
#18
Alexander Herholt, Ben Brankatschk, Nirmal Kannaiyan, Sergi Papiol, Sven P Wichert, Michael C Wehr, Moritz J Rossner
Neuronal signal transduction shapes brain function and malfunction may cause mental disorders. Despite the existence of functional genomics screens for proliferation and toxicity, neuronal signalling has been difficult to address so far. To overcome this limitation, we developed a pooled screening assay which combines barcoded activity reporters with pooled genetic perturbation in a dual-expression adeno-associated virus (AAV) library. With this approach, termed pathScreener, we comprehensively dissect signalling pathways in postmitotic neurons...
December 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30513195/a-robust-and-all-inclusive-pipeline-for-shuffling-of-adeno-associated-viruses-aav
#19
Anne-Kathrin Herrmann, Christian Bender, Eike Kienle, Stefanie Grosse, Jihad El Andari, Julia Botta, Nina Schürmann, Ellen Wiedtke, Dominik Niopek, Dirk Grimm
Adeno-associated viruses (AAV) are attractive templates for engineering of synthetic gene delivery vectors. A particularly powerful technology for breeding of novel vectors with improved properties is DNA family shuffling, i.e., generation of chimeric capsids by homology-driven DNA recombination. Here, to make AAV DNA shuffling available to a wider community, we present a robust experimental and bioinformatical pipeline comprising: (i) standardized and partially codon-optimized plasmids carrying 12 different AAV capsid genes; (ii) a scalable protocol including troubleshooting guide for viral library production; and (iii) the freely available software SALANTO for comprehensive analysis of chimeric AAV DNA and protein sequences...
December 4, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/30510219/investigating-the-neuroprotective-effect-of-aav-mediated-%C3%AE-synuclein-overexpression-in-a-transgenic-model-of-synucleinopathy
#20
Dorian Sargent, Dominique Bétemps, Matthieu Drouyer, Jérémy Verchere, Damien Gaillard, Jean-Noël Arsac, Latifa Lakhdar, Anna Salvetti, Thierry Baron
Parkinson's disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases characterized by inclusions mainly composed of α-synuclein (α-syn) aggregates. The objective of this study was to investigate if β-synuclein (β-syn) overexpression could have beneficial effects by inhibiting the aggregation of α-syn. The M83 transgenic mouse is a model of synucleinopathy, which develops severe motor symptoms associated with aggregation of α-syn. M83 neonate or adult mice were injected with adeno-associated virus vectors carrying the human β-syn gene (AAVβ-syn) or green fluorescent protein gene (AAVGFP) using different injection sites...
December 3, 2018: Scientific Reports
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