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https://www.readbyqxmd.com/read/29344635/eradication-of-cervical-cancer-in-vivo-by-an-aav-vector-that-encodes-shrna-targeting-human-papillomavirus-type-16%C3%A2-e6-e7
#1
Naoto Sato, Yasushi Saga, Ryosuke Uchibori, Tomonori Tsukahara, Masashi Urabe, Akihiro Kume, Hiroyuki Fujiwara, Mitsuaki Suzuki, Keiya Ozawa, Hiroaki Mizukami
The major causative agent of cervical cancer is human papilloma virus (HPV); the viral proteins E6 and E7 induce carcinogenesis through the inactivation of the host tumor-suppressor gene. Therefore, the stable expression of specific inhibitors of E6 and E7 in cancer cells is expected to provide effective treatment for cervical cancer without affecting normal tissue. In this study, we propose a novel therapeutic approach using an adeno-associated virus (AAV) vector encoding short hairpin RNA (shRNA) against the oncoproteins E6 and E7 (shE6E7) of HPV type 16 (HPV‑16), termed AAV‑shE6E7...
January 15, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29343568/an-alternate-route-for-adeno-associated-virus-entry-independent-of-aavr
#2
Amanda M Dudek, Sirika Pillay, Andreas S Puschnik, Claude M Nagamine, Fang Cheng, Jianming Qiu, Jan E Carette, Luk H Vandenberghe
Determinants and mechanisms of cell attachment and entry steer the Adeno-Associated Virus (AAV) in its utility as a gene therapy vector. Thus far a systematic assessment of how diverse AAV serotypes engage their proteinaceous receptor AAVR (KIAA0319L) to establish transduction has been lacking, despite potential implications for cell and tissue tropism. Here, a large set of human and simian AAVs as well as in silico reconstructed ancestral AAV capsids were interrogated for AAVR usage. We identified a distinct AAV capsid lineage comprised of AAV4 and AAVrh32...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29342044/elevated-level-of-myeloperoxidase-deoxyribonucleic-acid-complex-in-the-middle-ear-fluid-obtained-from-patients-with-otitis-media-associated-with-antineutrophil-cytoplasmic-antibody-associated-vasculitis
#3
Shinya Morita, Yuji Nakamaru, Daigo Nakazawa, Fumihiko Hattanda, Haruki Shida, Yoshihiro Kusunoki, Kanako Watanabe, Sakiko Masuda, Dai Takagi, Masanobu Suzuki, Kimiko Hoshino, Atsushi Fukuda, Utano Tomaru, Akihiro Homma, Akihiro Ishizu
OBJECTIVE: The purpose was to explore the presence of myeloperoxidase (MPO)-deoxyribonucleic acid (DNA) complex as a surrogate marker of neutrophil extracellular traps (NETs) in the middle ear fluid, and to clarify the correlation between its quantifiable level and hearing outcome in patients with otitis media associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). STUDY DESIGN: Prospective study. SETTING: Tertiary referral center...
January 16, 2018: Otology & Neurotology
https://www.readbyqxmd.com/read/29340623/pharmacokinetics-of-rituximab-and-clinical-outcomes-in-patients-with-anti-neutrophil-cytoplasmic-antibody-associated-vasculitis
#4
Divi Cornec, Brian F Kabat, John R Mills, Melissa Cheu, Amber M Hummel, Darrell R Schroeder, Matthew D Cascino, Paul Brunetta, David L Murray, Melissa R Snyder, Fernando Fervenza, Gary S Hoffman, Cees G M Kallenberg, Carol A Langford, Peter A Merkel, Paul A Monach, Philip Seo, Robert F Spiera, E William St Clair, John H Stone, David R Barnidge, Ulrich Specks
Objectives: To study the determinants of the pharmacokinetics (PK) of rituximab (RTX) in patients with ANCA-associated vasculitis (AAV) and its association with clinical outcomes. Methods: This study included data from 89 patients from the RTX in AAV trial who received the full dose of RTX (four weekly infusions of 375 mg/m2). RTX was quantified at weeks 2, 4, 8, 16 and 24, and summarized by computing the trapezoidal area under the curve. We explored potential determinants of the PK-RTX, and analysed its association with clinical outcomes: achievement of remission at 6 months, duration of B-cell depletion and time to relapse in patients who achieved complete remission...
January 10, 2018: Rheumatology
https://www.readbyqxmd.com/read/29339053/upregulation-of-nlrp3-via-stat3-dependent-histone-acetylation-contributes-to-painful-neuropathy-induced-by-bortezomib
#5
Cui-Cui Liu, Zhu-Xi Huang, Xiao Li, Kai-Feng Shen, Meng Liu, Han-Dong Ouyang, Su-Bo Zhang, Yu-Ting Ruan, Xiao-Long Zhang, Shao-Ling Wu, Wen-Jun Xin, Chao Ma
Painful neuropathy, as a severe side effect of chemotherapeutic bortezomib, is the most common reason for treatment discontinuation. However, the mechanism by which administration of bortezomib leads to painful neuropathy remains unclear. In the present study, we found that application of bortezomib significantly increased the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and phosphorylated signal transducer and activator of transcription-3 (STAT3) in dorsal root ganglion (DRG). Intrathecal injection of NLRP3 siRNA significantly prevented the mechanical allodynia induced by bortezomib treatment, and intrathecal injection of recombinant adeno-associated virus vector encoding NLRP3 markedly decreased paw withdrawal threshold of naive rats...
January 12, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29337147/neuronal-pten-deletion-in-adult-cortical-neurons-triggers-progressive-growth-of-cell-bodies-dendrites-and-axons
#6
Erin A Gallent, Oswald Steward
Deletion of the phosphatase and tensin (PTEN) gene in neonatal mice leads to enlargement of the cell bodies of cortical motoneurons (CMNs) in adulthood (Gutilla et al., 2016). Here, we assessed whether PTEN deletion in adult mice would trigger growth of mature neurons. PTEN was deleted by injecting AAV-Cre into the sensorimotor cortex of adult transgenic mice with a lox-P flanked exon 5 of the PTEN gene and Cre-dependent reporter gene tdTomato. PTEN-deleted CMN's identified by tdT expression and retrograde labeling with fluorogold (FG) were significantly enlarged four months following PTEN deletion, and continued to increase in size through the latest time intervals examined (12-15 months post-deletion)...
January 11, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29336783/bronchiectasis-is-highly-prevalent-in-anti-mpo-anca-associated-vasculitis-and-is-associated-with-a-distinct-disease-presentation
#7
Antoine Néel, Alexandra Espitia-Thibault, Pierre-Paul Arrigoni, Christelle Volteau, Marie Rimbert, Agathe Masseau, Christian Agard, Fadi Fakhouri, Renan Liberge, Mohamed Hamidou
OBJECTIVES: To assess the prevalence of bronchiectasis in a Western cohort with ANCA-positive granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) and its correlations with disease presentation and outcome. METHODS: Retrospective study of ANCA-associated vasculitis (AAV) patients followed at Nantes University Hospital (2005-2015). Clinical, biological, and follow-up data were collected through chart review. Two experienced radiologists blinded to the clinical data interpreted chest high-resolution CTs according to the Feischner Society criteria...
December 7, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/29335006/genetic-dissection-of-the-neuro-glio-vascular-machinery-in-the-adult-brain
#8
Gregory W Kirschen, Rachel Kéry, Hanxiao Liu, Afrinash Ahamad, Liang Chen, Wendy Akmentin, Ramya Kumar, Joel Levine, Qiaojie Xiong, Shaoyu Ge
The adult brain actively controls its metabolic homeostasis via the circulatory system at the blood brain barrier interface. The mechanisms underlying the functional coupling from neuron to vessel remain poorly understood. Here, we established a novel method to genetically isolate the individual components of this coupling machinery using a combination of viral vectors. We first discovered a surprising non-uniformity of the glio-vascular structure in different brain regions. We carried out a viral injection screen and found that intravenous Canine Adenovirus 2 (CAV2) preferentially targeted perivascular astrocytes throughout the adult brain, with sparing of the hippocampal hilus from infection...
January 15, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29329879/mir-134-modulates-chronic-stress-induced-structural-plasticity-and-depression-like-behaviors-via-downregulation-of-limk1-cofilin-signaling-in-rats
#9
Cuiqin Fan, Xiuzhi Zhu, Qiqi Song, Peng Wang, Zhuxi Liu, Shu Yan Yu
Increasing evidence has suggested that depression is a neuropsychiatric condition associated with neuroplasticity within specific brain regions. However, the mechanisms by which neuroplasticity exerts its effects in depression remain largely uncharacterized. In the present study we show that chronic stress effectively induces depression-like behaviors in rats, an effect which was associated with structural changes in dendritic spines and synapse abnormalities within neurons of the ventromedial prefrontal cortex (vmPFC)...
January 9, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29326962/emerging-issues-in-aav-mediated-in%C3%A2-vivo-gene-therapy
#10
REVIEW
Pasqualina Colella, Giuseppe Ronzitti, Federico Mingozzi
In recent years, the number of clinical trials in which adeno-associated virus (AAV) vectors have been used for in vivo gene transfer has steadily increased. The excellent safety profile, together with the high efficiency of transduction of a broad range of target tissues, has established AAV vectors as the platform of choice for in vivo gene therapy. Successful application of the AAV technology has also been achieved in the clinic for a variety of conditions, including coagulation disorders, inherited blindness, and neurodegenerative diseases, among others...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29325457/synthetic-adeno-associated-viral-vector-efficiently-targets-mouse-and-non-human-primate-retina-in-vivo
#11
Livia S Carvalho, Ru Xiao, Sarah Wassmer, Aliete Langsdorf, Eric Zinn, Simon Pacouret, Samiksha Shah, Jason I Comander, Leo Kim, Laurence Lim, Luk H Vandenberghe
Gene therapy is a promising approach in the treatment of inherited and common complex disorders of the retina. Preclinical and clinical studies have validated the use of adeno-associated viral vectors (AAV) as a safe and efficient delivery vehicle for gene transfer. RPE and rods, and to a lesser extent, cone photoreceptors can be efficiently targeted with AAV. Other retinal cell types however are more challenging targets. The aim of this study was to characterize the transduction profile and efficiency of in silico designed, synthetic Anc80 AAVs for retinal gene transfer...
January 12, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29322343/rituximab-for-anti-neutrophil-cytoplasmic-antibodies-associated-vasculitis-experience-of-a-single-center-and-systematic-review-of-non-randomized-studies
#12
Gizem Ayan, Sinem Nihal Esatoglu, Gulen Hatemi, Serdal Ugurlu, Emire Seyahi, Melike Melikoglu, Izzet Fresko, Huri Ozdogan, Sebahattin Yurdakul, Vedat Hamuryudan
Rituximab (RTX) is becoming a standard treatment for patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) but heterogeneity exists regarding its use. We present our uncontrolled experience with RTX in patients with refractory AAV and also the results of a systematic review of non-randomized studies on RTX in AAV patients. We retrospectively reviewed the records of AAV patients treated with RTX following an inadequate response to immunosuppressives between 2011 and 2015. The systematic review covered all English articles listed in PubMed until June 2017...
January 10, 2018: Rheumatology International
https://www.readbyqxmd.com/read/29318471/aav-mediated-gene-delivery-of-the-calreticulin-anti-angiogenic-domain-inhibits-ocular-neovascularization
#13
Leilei Tu, Jiang-Hui Wang, Veluchamy A Barathi, Selwyn M Prea, Zheng He, Jia Hui Lee, James Bender, Anna E King, Grant J Logan, Ian E Alexander, Youn-Shen Bee, Ming-Hong Tai, Gregory J Dusting, Bang V Bui, Jingxiang Zhong, Guei-Sheung Liu
Ocular neovascularization is a common pathological feature in diabetic retinopathy and neovascular age-related macular degeneration that can lead to severe vision loss. We evaluated the therapeutic efficacy of a novel endogenous inhibitor of angiogenesis, the calreticulin anti-angiogenic domain (CAD180), and its functional 112-residue fragment, CAD-like peptide 112 (CAD112), delivered using a self-complementary adeno-associated virus serotype 2 (scAAV2) in rodent models of oxygen-induced retinopathy and laser-induced choroidal neovascularization...
January 9, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29317724/rfx1-and-rfx3-transcription-factors-interact-with-the-d-sequence-of-adeno-associated-virus-inverted-terminal-repeat-and-regulate-aav-transduction
#14
Laura Julien, Julie Chassagne, Cécile Peccate, Stéphanie Lorain, France Piétri-Rouxel, Olivier Danos, Sofia Benkhelifa-Ziyyat
Adeno-associated virus (AAV) transduction efficiency depends on the way in which cellular proteins process viral genomes in the nucleus. In this study, we have investigated the binding of nuclear proteins to the double stranded D (dsD) sequence of the AAV inverted terminal repeat (ITRs) by electromobility shift assay. We present here several lines of evidence that transcription factors belonging to the RFX protein family bind specifically and selectively to AAV2 and AAV1 dsD sequences. Using supershift experiments, we characterize complexes containing RFX1 homodimers and RFX1/RFX3 heterodimers...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316814/biology-of-the-adrenal-gland-cortex-obviates-effective-use-of-adeno-associated-virus-vectors-to-treat-hereditary-adrenal-disorders
#15
Sandra Markmann, Bishnu P De, Jasmine Reid, Clarisse Jose, Jonathan B Rosenberg, Philip Leopold, Stephen M Kaminsky, Dolan Sondhi, Odelya E Pagovich, Ronald G Crystal
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder occurring in 1:10,000-1:20,000 live births. In >95% of the cases, CAH results from mutations in the CYP21A2 gene, encoding the adrenal steroid enzyme 21-hydroxylase (21OH). Cardinal phenotypic features of CAH include genital ambiguity and sexual precocity, and in severe cases, neonatal salt loss and death. Current standard of care consists of life-long oral steroid replacement to reverse the cortisol deficiency. Although significant advances in the treatment of CAH have been made, the burden of a life-long therapeutic intervention is not ideal for quality of life...
January 9, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29316812/aavrh10-gene-therapy-ameliorates-central-and-peripheral-nervous-system-disease-in-canine-globoid-cell-leukodystrophy-krabbe-disease
#16
Allison M Bradbury, Mohammad A Rafi, Jessica Bagel, Becky K Brisson, Michael S Marshall, Jill Pesayco Salvador, Xuntian Jiang, Gary P Swain, Maria L Prociuk, Patricia O'Donnell, Caitlin Fitzgerald, Daniel S Ory, Ernesto R Bongarzone, G Diane Shelton, David A Wenger, Charles Vite
Globoid cell leukodystrophy (GLD), or Krabbe disease, is an inherited, neurologic disorder that results from deficiency of a lysosomal enzyme, galactosylceramidase (GALC). Most commonly, deficits of GALC result in widespread central and peripheral nervous system (CNS, PNS) demyelination and death in affected infants typically by 2 years of age. Hematopoietic stem cell transplantation is the current standard of care in children diagnosed prior to symptom onset; however, disease correction is incomplete. Herein we present the first adeno-associated virus (AAV) gene therapy experiments in a naturally occurring canine model of GLD that closely recapitulates the clinical disease progression, neuropathological alterations, and biochemical abnormalities observed in human patients...
January 9, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29310663/%C3%AE-synuclein-accumulation-and-gba-deficiency-due-to-l444p-gba-mutation-contributes-to-mptp-induced-parkinsonism
#17
Seung Pil Yun, Donghoon Kim, Sangjune Kim, SangMin Kim, Senthilkumar S Karuppagounder, Seung-Hwan Kwon, Saebom Lee, Tae-In Kam, Suhyun Lee, Sangwoo Ham, Jae Hong Park, Valina L Dawson, Ted M Dawson, Yunjong Lee, Han Seok Ko
BACKGROUND: Mutations in glucocerebrosidase (GBA) cause Gaucher disease (GD) and increase the risk of developing Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Since both genetic and environmental factors contribute to the pathogenesis of sporadic PD, we investigated the susceptibility of nigrostriatal dopamine (DA) neurons in L444P GBA heterozygous knock-in (GBA +/L444P ) mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective dopaminergic mitochondrial neurotoxin...
January 8, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29308612/stable-knockdown-of-adenosine-kinase-by-lentiviral-anti-adk-mir-shrnas-in-wharton-s-jelly-stem-cells
#18
Hajar Estiri, Ali Fallah, Masoud Soleimani, Abbas Aliaghaei, Fariba Karimzadeh, Shahnaz Babaei Abraki, Mohammad Hossein Ghahremani
OBJECTIVES: In this study, we describe an efficient approach for stable knockdown of adenosine kinase (ADK) using lentiviral system, in an astrocytoma cell line and in human Wharton's jelly mesenchymal stem cells (hWJMSCs). These sources of stem cells besides having multilineage differentiation potential and immunomodulatory activities, are easily available in unlimited numbers, do not raise ethical concerns and are attractive for gene manipulation and cell-based gene therapy. MATERIALS AND METHODS: In this experimental study, we targeted adenosine kinase mRNA at 3' and performed coding sequences using eight miR-based expressing cassettes of anti-ADK short hairpin RNA (shRNAs)...
April 2018: Cell Journal
https://www.readbyqxmd.com/read/29306061/structure-of-vagal-afferent-nerve-terminal-fibers-in-the-mouse-trachea
#19
Michal Hennel, Jana Harsanyiova, Fei Ru, Tomas Zatko, Mariana Brozmanova, Alzbeta Trancikova, Milos Tatar, Marian Kollarik
The structure of primary afferent nerve terminals profoundly influences their function. While the complex vagal airway nerve terminals (stretch receptors, cough receptors and neuroepithelial bodies) were thoroughly characterized, much less is known about the structure of airway nerves that do not form distinct complex terminals (often termed free nerve fibers). We selectively induced expression of GFP in vagal afferent nerves in the mouse by transfection with AAV-GFP virus vector and visualized nerve terminals in the trachea by whole organ confocal imaging...
January 3, 2018: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/29302202/aav-mediated-astrocyte-specific-gene-expression-under-human-aldh1l1-promoter-in-mouse-thalamus
#20
Wuhyun Koh, Yongmin Mason Park, Seung Eun Lee, C Justin Lee
Adeno-associated virus (AAV)-mediated gene delivery has been proposed to be an essential tool of gene therapy for various brain diseases. Among several cell types in the brain, astrocyte has become a promising therapeutic target for brain diseases, as more and more contribution of astrocytes in pathophysiology has been revealed. Until now, genetically targeting astrocytes has been possible by utilizing the glial fibrillary acidic protein (GFAP) promoter. In some brain areas including thalamus, however, the GFAP expression in astrocytes is reported to be low, making it difficult to genetically target astrocytes using GFAP promoter...
December 2017: Experimental Neurobiology
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