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adeno associated virus

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https://www.readbyqxmd.com/read/28533489/sirtuin-6-inhibits-epithelial-to-mesenchymal-transition-during-idiopathic-pulmonary-fibrosis-via-inactivating-tgf-%C3%AE-1-smad3-signaling
#1
Kunming Tian, Panpan Chen, Zhiping Liu, Shutian Si, Qian Zhang, Yong Mou, Lianyong Han, Qin Wang, Xue Zhou
Sirt6 which is implicated in the control of aging, cancer, and metabolism, has been shown to have anti-fibrosis function in heart and liver. However, whether Sirt6 inhibits idiopathic pulmonary fibrosis remains elusive. Epithelial to mesenchymal transition has been found to be involved in the pathogenesis of idiopathic pulmonary fibrosis. In the present study, forced expression of Sirt6 significantly abrogated TGF-β1-induced epithelial to mesenchymal transition-like phenotype and cell behaviors in A549 cells...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28527664/a-new-hdv-mouse-model-identifies-mitochondrial-antiviral-signaling-protein-mavs-as-a-key-player-in-ifn-%C3%AE-induction
#2
Lester Suárez-Amarán, Carla Usai, Marianna Di Scala, Cristina Godoy, Yi Ni, Mirja Hommel, Laura Palomo, Víctor Segura, Cristina Olagüe, Africa Vales, Alicia Ruiz-Ripa, Maria Buti, Eduardo Salido, Jesús Prieto, Stephan Urban, Francisco Rodríguez-Frias, Rafael Aldabe, Gloria González-Aseguinolaza
BACKGROUND & AIMS: Studying hepatitis delta virus (HDV) and developing new treatments is hampered by the limited availability of small animal models. Here a description of a robust mouse model of HDV infection that mimics several important characteristics of the human disease is presented. METHODS: HDV- and HBV-replication competent genomes were delivered to the mouse liver using adeno-associated viruses (AAV) (AAV-HDV and AAV-HBV). Viral load, antigen expression and genomes were quantified at different time points after AAV injection...
May 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28526436/intracranial-il-17a-overexpression-decreases-cerebral-amyloid-angiopathy-by-upregulation-of-abca1-in-an-animal-model-of-alzheimer-s-disease
#3
Junling Yang, Jinghong Kou, Robert Lalonde, Ken-Ichiro Fukuchi
Neuroinflammation is a pervasive feature of Alzheimer's disease (AD) and characterized by activated microglia, increased proinflammatory cytokines and/or infiltrating immune cells. T helper 17 (Th17) cells are found in AD brain parenchyma and interleukin-17A (IL-17A) is identified around deposits of aggregated amyloid β protein (Aβ). However, the role of IL-17A in AD pathogenesis remains elusive. We overexpressed IL-17A in an AD mouse model via recombinant adeno-associated virus serotype 5 (rAAV5)-mediated intracranial gene delivery...
May 17, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28525804/recombinant-adeno-associated-virus-vector-carrying-the-thrombomodulin-lectin-like-domain-for-the-treatment-of-abdominal-aortic-aneurysm
#4
Chao-Han Lai, Kuan-Chieh Wang, Cheng-Hsiang Kuo, Fang-Tzu Lee, Tsung-Lin Cheng, Bi-Ing Chang, Yu-Jen Yang, Guey-Yueh Shi, Hua-Lin Wu
BACKGROUND AND AIMS: Thrombomodulin (TM), through its lectin-like domain (TMD1), sequesters proinflammatory high-mobility group box 1 (HMGB1) to prevent it from engaging the receptor for advanced glycation end product (RAGE) that sustains inflammation and tissue damage. Our previous study demonstrated that short-term treatment with recombinant TM containing all the extracellular domains (i.e., rTMD123) inhibits HMGB1-RAGE signaling and confers protection against CaCl2-induced AAA formation...
March 18, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28515305/cell-cycle-dependent-expression-of-aav2-rep-in-hsv-1-co-infections-gives-rise-to-a-mosaic-of-cells-replicating-either-aav2-or-hsv-1
#5
Francesca D Franzoso, Michael Seyffert, Rebecca Vogel, Artur Yakimovich, Bruna de Andrade Pereira, Anita F Meier, Sereina O Sutter, Kurt Tobler, Bernd Vogt, Urs F Greber, Hildegard Büning, Mathias Ackermann, Cornel Fraefel
Adeno-associated virus 2 (AAV2) depends for productive replication on the simultaneous presence of a helper virus such as herpes simplex virus type 1 (HSV-1). At the same time, AAV2 efficiently blocks the replication of HSV-1, which would eventually limit its own replication by diminishing the helper virus reservoir. This discrepancy begs the question how AAV2 and HSV-1 can co-exist in a cell population. Here we show that in co-infected cultures, AAV2 DNA replication takes place almost exclusively in S/G2 cells, while HSV-1 DNA replication is restricted to G1...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28510482/rod-outer-segment-development-influences-aav-mediated-photoreceptor-transduction-after-subretinal-injection
#6
Lolita Petit, Shan Ma, Shun-Yun Cheng, Guangping Gao, Claudio Punzo
Vectors based on the adeno-associated virus (AAV) are currently the preferred tools for delivering genes to photoreceptors (PR) in small and large animals. AAVs have been applied successfully in various models of PR dystrophies. However, unknown barriers still limit AAV's efficient application in several forms of severe PR degenerations, due to insufficient transgene expression and/or treated cells at the time of injection. Optimizations of PR gene therapy strategies will likely benefit from the identification of the cellular factors that influence PR transduction...
May 16, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28506534/neurod1-instructs-neuronal-conversion-in-non-reactive-astrocytes
#7
Rebecca Brulet, Taito Matsuda, Ling Zhang, Carlos Miranda, Mauro Giacca, Brian K Kaspar, Kinichi Nakashima, Jenny Hsieh
Currently, all methods for converting non-neuronal cells into neurons involve injury to the brain; however, whether neuronal transdifferentiation can occur long after the period of insult remains largely unknown. Here, we use the transcription factor NEUROD1, previously shown to convert reactive glial cells to neurons in the cortex, to determine whether astrocyte-to-neuron transdifferentiation can occur under physiological conditions. We utilized adeno-associated virus 9 (AAV9), which crosses the blood-brain barrier without injury, to deliver NEUROD1 to astrocytes through an intravascular route...
May 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28506256/aav-vector-distribution-in-the-mouse-respiratory-tract-following-four-different-methods-of-administration
#8
Lisa A Santry, Joelle C Ingrao, Darrick L Yu, Jondavid G de Jong, Laura P van Lieshout, Geoffrey A Wood, Sarah K Wootton
BACKGROUND: Targeted delivery of gene therapy vectors to the mouse respiratory tract is often performed via intranasal or intratracheal administration; however, there can be a great deal of variability between these methods, which could potentially influence experimental results. Improving the accuracy and precision of lung delivery will not only reduce the number of animals required to detect statistically significant differences, but may reduce the variability of studies from different laboratories...
May 15, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28504688/accelerated-atherosclerosis-development-in-c57bl6-mice-by-overexpressing-aav-mediated-pcsk9-and-partial-carotid-ligation
#9
Sandeep Kumar, Dong-Won Kang, Amir Rezvan, Hanjoong Jo
Studying the role of a particular gene in atherosclerosis typically requires a time-consuming and often difficult process of generating double knockouts or transgenics on ApoE(-/-) or LDL receptor (LDLR)(-/-) background. Recently, it was reported that adeno-associated-virus-8 (AAV8)-mediated overexpression of PCSK9 (AAV8-PCSK9) rapidly induced hyperlipidemia. However, using this method in C57BL6 wild-type (C57) mice, it took ~3 months to develop atherosclerosis. Our partial carotid ligation model is used to rapidly develop atherosclerosis by inducing disturbed flow in the left common carotid artery within 2 weeks in ApoE(-/-) or LDLR(-/-) mice...
May 15, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28504668/hla-e-expressing-pluripotent-stem-cells-escape-allogeneic-responses-and-lysis-by-nk-cells
#10
Germán G Gornalusse, Roli K Hirata, Sarah E Funk, Laura Riolobos, Vanda S Lopes, Gabriel Manske, Donna Prunkard, Aric G Colunga, Laïla-Aïcha Hanafi, Dennis O Clegg, Cameron Turtle, David W Russell
Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the rejection of pluripotent stem cell (PSC)-derived products in allogeneic recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface expression of all class I molecules, but leaves the cells vulnerable to lysis by natural killer (NK) cells. Here we show that this 'missing-self' response can be prevented by forced expression of minimally polymorphic HLA-E molecules. We use adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the B2M locus in human PSCs in a manner that confers inducible, regulated, surface expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M and a peptide antigen), without surface expression of HLA-A, B or C...
May 15, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28504553/aavs1-targeted-plasmid-integration-in-aav-producer-cell-lines
#11
Yuxia Luo, Amy Frederick, John M Martin, Abraham Scaria, Seng H Cheng, Donna Armentano, Samuel C Wadsworth, Karen A Vincent
Adeno-associated virus (AAV) producer cell lines are created via transfection of HeLaS3 cells with a single plasmid containing three components (the vector sequence, the AAV rep and cap genes, and a selectable marker gene). As this plasmid contains both the cis (Rep binding sites) and trans (Rep protein encoded by the rep gene) elements required for site-specific integration, it was predicted that plasmid integration might occur within the AAVS1 locus on human chromosome 19 (chr19). The objective of this study was to investigate whether integration in AAVS1 might be correlated with vector yield...
April 14, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28503441/applications-of-crispr-cas9-in-retinal-degenerative-diseases
#12
REVIEW
Ying-Qian Peng, Luo-Sheng Tang, Shigeo Yoshida, Ye-Di Zhou
Gene therapy is a potentially effective treatment for retinal degenerative diseases. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has been developed as a new genome-editing tool in ophthalmic studies. Recent advances in researches showed that CRISPR/Cas9 has been applied in generating animal models as well as gene therapy in vivo of retinitis pigmentosa (RP) and leber congenital amaurosis (LCA). It has also been shown as a potential attempt for clinic by combining with other technologies such as adeno-associated virus (AAV) and induced pluripotent stem cells (iPSCs)...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28500077/alternative-start-sites-downstream-of-nonsense-mutations-drive-antigen-presentation-and-tolerance-induction-to-c-terminal-epitopes
#13
Scott N Ashley, Suryanarayan Somanathan, Christian Hinderer, Maxwell Arias, Deirdre McMenamin, Christine Draper, James M Wilson
CTL responses to the transgene product remain an active area of concern for the gene therapy field. A patient's underlying genetic mutation may influence the qualitative nature of these potentially destructive T cell responses. Individuals with a mutation that introduces a premature termination codon (PTC) that prevents synthesis of the full-length peptide are considered more likely to mount a transgene-specific T cell response because of a lack of immune tolerance to C-terminal epitopes as a consequence of absent endogenous Ag presentation...
May 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28497072/improved-mecp2-gene-therapy-extends-the-survival-of-mecp2-null-mice-without-apparent-toxicity-after-intracisternal-delivery
#14
Sarah E Sinnett, Ralph D Hector, Kamal K E Gadalla, Clifford Heindel, Daphne Chen, Violeta Zaric, Mark E S Bailey, Stuart R Cobb, Steven J Gray
Intravenous administration of adeno-associated virus serotype 9 (AAV9)/hMECP2 has been shown to extend the lifespan of Mecp2(-/y) mice, but this delivery route induces liver toxicity in wild-type (WT) mice. To reduce peripheral transgene expression, we explored the safety and efficacy of AAV9/hMECP2 injected into the cisterna magna (ICM). AAV9/hMECP2 (1 × 10(12) viral genomes [vg]; ICM) extended Mecp2(-/y) survival but aggravated hindlimb clasping and abnormal gait phenotypes. In WT mice, 1 × 10(12) vg of AAV9/hMECP2 induced clasping and abnormal gait...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28490573/dok7-gene-therapy-enhances-motor-activity-and-life-span-in-als-model-mice
#15
Sadanori Miyoshi, Tohru Tezuka, Sumimasa Arimura, Taro Tomono, Takashi Okada, Yuji Yamanashi
Amyotrophic lateral sclerosis (ALS) is a progressive, multifactorial motor neurodegenerative disease with severe muscle atrophy. The glutamate release inhibitor riluzole is the only medication approved by the FDA, and prolongs patient life span by a few months, testifying to a strong need for new treatment strategies. In ALS, motor neuron degeneration first becomes evident at the motor nerve terminals in neuromuscular junctions (NMJs), the cholinergic synapse between motor neuron and skeletal muscle; degeneration then progresses proximally, implicating the NMJ as a therapeutic target...
May 10, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28490211/aav-vectors-and-stem-cells-friends-or-foes
#16
Nolan Brown, Liujiang Song, Nageswara Rao Kollu, Matt Hirsch
The infusion of healthy stem cells into a patient, termed stem cell therapy, has shown great promise for the treatment of genetic and non-genetic diseases including mucopolysaccharidosis type 1, Parkinson's disease, multiple sclerosis, numerous immunodeficiency disorders, and aplastic anemia. Stem cells for cell therapy can be collected from the patient (autologous) or collected from another "healthy" individual (allogeneic). The use of allogenic stem cells is accompanied with the potentially fatal risk that the transplanted donor T cells will reject the patient's cells, a process termed graft-versus-host disease...
May 10, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28490200/human-bocavirus-type-1-capsid-facilitates-the-transduction-of-ferret-airways-by-adeno-associated-virus-genomes
#17
Ziying Yan, Zehua Feng, Xingshen Sun, Yulong Zhang, Wei Zou, Zekun Wang, Chandler Jensen-Cody, Bo Liang, Soo-Yeun Park, Jianming Qiu, John F Engelhardt
Human bocavirus type-1 (HBoV1) has a high tropism for the apical membrane of human airway epithelia. The packaging of a recombinant adeno-associated virus 2 (rAAV2) genome into HBoV1 capsid produces a chimeric vector (rAAV2/HBoV1) that also efficiently transduces human airway epithelia. As such, this vector is attractive for use in gene therapies to treat lung diseases such as cystic fibrosis. However, preclinical development of rAAV2/HBoV1 vectors has been hindered by the fact that humans are the only known host for HBoV1 infection...
May 10, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28488944/a-scalable-and-accurate-method-for-quantifying-vector-genomes-of-recombinant-adeno-associated-viruses-in-crude-lysate
#18
Jianzhong Ai, Raed Ibraheim, Phillip W L Tai, Guangping Gao
Increasing interest and application of recombinant adeno-associated viruses (rAAVs) in basic and clinical research have urged efforts to improve rAAV production quality and yield. Standard vector production workflows call for genome titration of purified vectors at the endpoint of production to assess yield. Unfortunately, quality control measures for preparations during mid-production steps and economical means to assess the fidelity of multiple batches of rAAV preparations are lacking. Here we describe a scalable and accurate method for the direct quantitative polymerase chain reaction (qPCR) titration of rAAV genomes in crude lysate...
April 13, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28482158/magnetically-guided-viral-transduction-of-gene-based-sensitization-for-localized-photodynamic-therapy-to-overcome-multidrug-resistance-in-breast-cancer-cells
#19
Zi-Xian Liao, Ivan M Kempson, Yu-Chen Fa, Meng-Chia Liu, Li-Chen Hsieh, Kuo-Yen Huang, Li-Feng Wang
Chemotherapy represents a conventional treatment for many cancers at different stages and is either solely prescribed or concomitant to surgery, radiotherapy, or both. However, treatment is tempered in instances of acquired drug resistance in response to either chemotherapy or targeted therapy, leading to therapeutic failure. To overcome this challenge, many studies focus on how cancer cells manipulate their genomes and metabolism to prevent drug influx and facilitate the efflux of accumulated chemotherapy drugs...
May 15, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28481222/hepatic-metal-ion-transporter-zip8-regulates-manganese-homeostasis-and-manganese-dependent-enzyme-activity
#20
Wen Lin, David R Vann, Paschalis-Thomas Doulias, Tao Wang, Gavin Landesberg, Xueli Li, Emanuela Ricciotti, Rosario Scalia, Miao He, Nicholas J Hand, Daniel J Rader
Genetic variants at the solute carrier family 39 member 8 (SLC39A8) gene locus are associated with the regulation of whole-blood manganese (Mn) and multiple physiological traits. SLC39A8 encodes ZIP8, a divalent metal ion transporter best known for zinc transport. Here, we hypothesized that ZIP8 regulates Mn homeostasis and Mn-dependent enzymes to influence metabolism. We generated Slc39a8-inducible global-knockout (ZIP8-iKO) and liver-specific-knockout (ZIP8-LSKO) mice and observed markedly decreased Mn levels in multiple organs and whole blood of both mouse models...
May 8, 2017: Journal of Clinical Investigation
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