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https://www.readbyqxmd.com/read/28214886/adenovirus-vector-harboring-the-hbcag-and-tripeptidyl-peptidase-ii-genes-induces-potent-cellular-immune-responses-in-vivo
#1
Quanhui Tan, Siyuan Ma, Jianjun Hu, Xiaohua Chen, Yongsheng Yu, Zhenghao Tang, Guoqin Zang
BACKGROUND: Chronic hepatitis B virus (HBV) infection is associated with a weak but specific cellular immune response of the host to HBV. Tripeptidyl peptidaseⅡ (TPPⅡ), an intracellular macromolecule and proteolytic enzyme, plays an important complementary and compensatory role for the proteasome during viral protein degradation and major histocompatibility complex class I antigen presentation by inducing a specific cellular immune response in vivo. Based on a previous study, we aimed to explore the role of MHC class I antigen presentation in vivo and the mechanisms that may be involved...
January 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28214630/ph-and-reduction-dual-responsive-dipeptide-cationic-lipids-with-%C3%AE-tocopherol-hydrophobic-tail-for-efficient-gene-delivery
#2
Qiang Liu, Rong-Chuan Su, Wen-Jing Yi, Li-Ting Zheng, Shan-Shan Lu, Zhi-Gang Zhao
A series of tocopherol-based cationic lipid 3a-3f bearing a pH-sensitive imidazole moiety in the dipeptide headgroup and a reduction-responsive disulfide linkage were designed and synthesized. Acid-base titration of these lipids showed good buffering capacities. The liposomes formed from 3 and co-lipid 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) could efficiently bind and condense DNA into nanoparticles. Gel binding and HPLC assays confirmed the encapsulated DNA could release from lipoplexes 3 upon addition of 10 mM glutathione (GSH)...
February 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28213165/hbvcircle-a-novel-tool-to-investigate-hepatitis-b-virus-covalently-closed-circular-dna
#3
Zhipeng Yan, Jing Zeng, Youjun Yu, Kunlun Xiang, Hui Hu, Xue Zhou, Lili Gu, Li Wang, Jie Zhao, John A T Young, Lu Gao
BACKGROUND & AIMS: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) persists as a stable episome in infected hepatocytes and serves as a template for the transcription of all viral genes. Due to the narrow host range of HBV, the development of a robust mouse model that supports cccDNA-dependent viral replication is a key hurdle in the development of novel HBV therapeutics. This study aimed to develop a novel tool to investigate HBV cccDNA. METHODS: Through minicircle technology, HBVcircle, a recombinant cccDNA, was easily generated and extracted from a genetically engineered E...
February 14, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28212379/distribution-and-abundance-of-key-vectors-of-rift-valley-fever-and-other-arboviruses-in-two-ecologically-distinct-counties-in-kenya
#4
Rosemary Sang, Samwel Arum, Edith Chepkorir, Gladys Mosomtai, Caroline Tigoi, Faith Sigei, Olivia Wesula Lwande, Tobias Landmann, Hippolyte Affognon, Clas Ahlm, Magnus Evander
BACKGROUND: Rift Valley fever (RVF) is a mosquito-borne viral zoonosis of ruminants and humans that causes outbreaks in Africa and the Arabian Peninsula with significant public health and economic consequences. Humans become infected through mosquito bites and contact with infected livestock. The virus is maintained between outbreaks through vertically infected eggs of the primary vectors of Aedes species which emerge following rains with extensive flooding. Infected female mosquitoes initiate transmission among nearby animals, which amplifies virus, thereby infecting more mosquitoes and moving the virus beyond the initial point of emergence...
February 17, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28211908/the-n-terminal-domain-of-schmallenberg-virus-envelope-protein-gc-is-highly-immunogenic-and-can-provide-protection-from-infection
#5
Kerstin Wernike, Andrea Aebischer, Gleyder Roman-Sosa, Martin Beer
Schmallenberg virus (SBV) is transmitted by insect vectors, and therefore vaccination is one of the most important tools of disease control. In our study, novel subunit vaccines on the basis of an amino-terminal domain of SBV Gc of 234 amino acids ("Gc Amino") first were tested and selected using a lethal small animal challenge model and then the best performing formulations also were tested in cattle. We could show that neither E. coli expressed nor the reduced form of "Gc Amino" protected from SBV infection...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28208635/advances-in-non-viral-dna-vectors-for-gene-therapy
#6
Cinnamon L Hardee, Lirio Milenka Arévalo-Soliz, Benjamin D Hornstein, Lynn Zechiedrich
Uses of viral vectors have thus far eclipsed uses of non-viral vectors for gene therapy delivery in the clinic. Viral vectors, however, have certain issues involving genome integration, the inability to be delivered repeatedly, and possible host rejection. Fortunately, development of non-viral DNA vectors has progressed steadily, especially in plasmid vector length reduction, now allowing these tools to fill in specifically where viral or other non-viral vectors may not be the best options. In this review, we examine the improvements made to non-viral DNA gene therapy vectors, highlight opportunities for their further development, address therapeutic needs for which their use is the logical choice, and discuss their future expansion into the clinic...
February 10, 2017: Genes
https://www.readbyqxmd.com/read/28207788/self-complementary-adeno-associated-virus-serotype-6-mediated-knockdown-of-adamts4-induces-long-term-and-effective-enhancement-of-aggrecan-in-degenerative-human-nucleus-pulposus-cells-a-new-therapeutic-approach-for-intervertebral-disc-disorders
#7
Demissew Shenegelegn Mern, Anja Tschugg, Sebastian Hartmann, Claudius Thomé
Inhibition of intervertebral disc (IVD) degeneration, which is often accompanied by painful inflammatory and immunopathological processes, is challenging. Current IVD gene therapeutic approaches are based on adenoviral gene delivery systems, which are limited by immune reactions to their viral proteins. Their applications in IVDs near to sensitive neural structure could provoke toxicity and immunological side-effects with neurological deficits. Self-complementary adeno-associated virus (scAAV) vectors, which do not express any viral gene and are not linked with any known disease in humans, are attractive therapeutic gene delivery vectors in degenerative IVDs...
2017: PloS One
https://www.readbyqxmd.com/read/28207247/ortho-methoxyphenols-as-convenient-oxidative-bioconjugation-reagents-with-application-to-site-selective-heterobifunctional-crosslinkers
#8
Adel M ElSohly, James Irving MacDonald, Nina B Hentzen, Ioana Laura Aanei, Kareem M El Muslemany, Matthew B Francis
The synthesis of complex protein-based bioconjugates has been facilitated greatly by recent developments in chemoselective methods for biomolecular modification. The oxidative coupling of o-aminophenols or catechols with aniline functional groups is chemoselective, mild, and rapid; however, the oxidatively sensitive nature of the electron-rich aromatics and the paucity of commercial sources pose some obstacles to the general use of these reactive strategies. Herein, we identify o-methoxyphenols as air-stable, commercially available derivatives that undergo efficient oxidative couplings with anilines in the presence of periodate as oxidant...
February 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28205516/a-viral-protease-relocalizes-in-the-presence-of-the-vector-to-promote-vector-performance
#9
Aurélie Bak, Andrea L Cheung, Chunling Yang, Steven A Whitham, Clare L Casteel
Vector-borne pathogens influence host characteristics relevant to host-vector contact, increasing pathogen transmission and survival. Previously, we demonstrated that infection with Turnip mosaic virus, a member of one of the largest families of plant-infecting viruses, increases vector attraction and reproduction on infected hosts. These changes were due to a single viral protein, NIa-Pro. Here we show that NIa-Pro responds to the presence of the aphid vector during infection by relocalizing to the vacuole...
February 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28202570/aav-mediated-delivery-of-optogenetic-constructs-to-the-macaque-brain-triggers-humoral-immune-responses
#10
Skyler D Mendoza, Yasmine El-Shamayleh, Gregory D Horwitz
Gene delivery to the primate central nervous system via recombinant adeno-associated viral vectors (AAV) allows neurophysiologists to control and observe neural activity precisely. A current limitation of this approach is variability in vector transduction efficiency. Low levels of transduction can foil experimental manipulations, prompting vector readministration. The ability to make multiple vector injections into the same animal, even in cases where successful vector transduction has already been achieved, is also desirable...
February 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28202388/viral-vector-reprogramming-of-adult-resident-striatal-oligodendrocytes-into-functional-neurons
#11
Marc S Weinberg, Hugh E Criswell, Sara K Powell, Aadra P Bhatt, Thomas J McCown
Recent advances suggest that in vivo reprogramming of endogenous cell populations provides a viable alternative for neuron replacement. Astrocytes and oligodendrocyte precursor cells can be induced to transdifferentiate into neurons in the CNS, but, in these instances, reprogramming requires either transgenic mice or retroviral-mediated gene expression. We developed a microRNA (miRNA)-GFP construct that in vitro significantly reduced the expression of polypyrimidine tract-binding protein, and, subsequently, we packaged this construct in a novel oligodendrocyte preferring adeno-associated virus vector...
February 12, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28202075/tick-borne-pathogens-induce-differential-expression-of-genes-promoting-cell-survival-and-host-resistance-in-ixodes-ricinus-cells
#12
Karen L Mansfield, Charlotte Cook, Richard J Ellis, Lesley Bell-Sakyi, Nicholas Johnson, Pilar Alberdi, José de la Fuente, Anthony R Fooks
BACKGROUND: There has been an emergence and expansion of tick-borne diseases in Europe, Asia and North America in recent years, including Lyme disease, tick-borne encephalitis and human anaplasmosis. The primary vectors implicated are hard ticks of the genus Ixodes. Although much is known about the host response to these bacterial and viral pathogens, there is limited knowledge of the cellular responses to infection within the tick vector. The bacterium Anaplasma phagocytophilum is able to bypass apoptotic processes in ticks, enabling infection to proceed...
February 15, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28198371/method-for-dual-viral-vector-mediated-crispr-cas9-gene-disruption-in-primary-human-endothelial-cells
#13
Haixia Gong, Menglin Liu, Jeff Klomp, Bradley J Merrill, Jalees Rehman, Asrar B Malik
Human endothelial cells (ECs) are widely used to study mechanisms of angiogenesis, inflammation, and endothelial permeability. Targeted gene disruption induced by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-Associated Protein 9 (Cas9) nuclease gene editing is potentially an important tool for definitively establishing the functional roles of individual genes in ECs. We showed that co-delivery of adenovirus encoding EGFP-tagged Cas9 and lentivirus encoding a single guide RNA (sgRNA) in primary human lung microvascular ECs (HLMVECs) disrupted the expression of the Tie2 gene and protein...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197596/amphiphilic-polymers-formed-from-ring-opening-polymerization-a-strategy-for-the-enhancement-of-gene-delivery
#14
Yi-Mei Zhang, Zheng Huang, Ji Zhang, Wan-Xia Wu, Yan-Hong Liu, Xiao-Qi Yu
Cationic liposomes and polymers are both important candidates for use as non-viral gene vectors. However, both of them have special shortcomings and application limits. This work is devoted to the combination of advantages of liposomes and polymers. The ring-opening polymerization strategy was used for the preparation of amphiphilic polymers from cyclen-based cationic small lipids. The non-hydrophobic polymer and the corresponding lipids were also prepared for performing structure-activity relationship studies...
February 15, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28197125/rna-interference-of-human-%C3%AE-synuclein-in-mouse
#15
Young-Cho Kim, Adam Miller, Livia C R F Lins, Sang-Woo Han, Megan S Keiser, Ryan L Boudreau, Beverly L Davidson, Nandakumar S Narayanan
α-Synuclein is postulated to play a key role in the pathogenesis of Parkinson's disease (PD). Aggregates of α-synuclein contribute to neurodegeneration and cell death in humans and in mouse models of PD. Here, we use virally mediated RNA interference to knockdown human α-synuclein in mice. We used an siRNA design algorithm to identify eight siRNA sequences with minimal off-targeting potential. One RNA-interference sequence (miSyn4) showed maximal protein knockdown potential in vitro. We then designed AAV vectors expressing miSyn4 and injected them into the mouse substantia nigra...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28196962/spatial-and-temporal-analysis-of-alphavirus-replication-and-assembly-in-mammalian-and-mosquito-cells
#16
Joyce Jose, Aaron B Taylor, Richard J Kuhn
Sindbis virus (SINV [genus Alphavirus, family Togaviridae]) is an enveloped, mosquito-borne virus. Alphaviruses cause cytolytic infections in mammalian cells while establishing noncytopathic, persistent infections in mosquito cells. Mosquito vector adaptation of alphaviruses is a major factor in the transmission of epidemic strains of alphaviruses. Though extensive studies have been performed on infected mammalian cells, the morphological and structural elements of alphavirus replication and assembly remain poorly understood in mosquito cells...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28196735/gtl001-and-bivalent-cyaa-based-therapeutic-vaccine-strategies-against-human-papillomavirus-and-other-tumor-associated-antigens-induce-effector-and-memory-t-cell-responses-that-inhibit-tumor-growth
#17
Michaël Esquerré, Marie Momot, Anne Goubier, Christophe Gonindard, Stéphane Leung-Theung-Long, Yolande Misseri, Marie-Christine Bissery
GTL001 is a bivalent therapeutic vaccine containing human papillomavirus (HPV) 16 and HPV18 E7 proteins inserted in the Bordetella pertussis adenylate cyclase (CyaA) vector intended to prevent cervical cancer in HPV-infected women with normal cervical cytology or mild abnormalities. To be effective, therapeutic cervical cancer vaccines should induce both a T cell-mediated effector response against HPV-infected cells and a robust CD8(+) T-cell memory response to prevent potential later infection. We examined the ability of GTL001 and related bivalent CyaA-based vaccines to induce, in parallel, effector and memory CD8(+) T-cell responses to both vaccine antigens...
February 10, 2017: Vaccine
https://www.readbyqxmd.com/read/28195574/muscle-specific-crispr-cas9-dystrophin-gene-editing-ameliorates-pathophysiology-in-a-mouse-model-for-duchenne-muscular-dystrophy
#18
Niclas E Bengtsson, John K Hall, Guy L Odom, Michael P Phelps, Colin R Andrus, R David Hawkins, Stephen D Hauschka, Joel R Chamberlain, Jeffrey S Chamberlain
Gene replacement therapies utilizing adeno-associated viral (AAV) vectors hold great promise for treating Duchenne muscular dystrophy (DMD). A related approach uses AAV vectors to edit specific regions of the DMD gene using CRISPR/Cas9. Here we develop multiple approaches for editing the mutation in dystrophic mdx(4cv) mice using single and dual AAV vector delivery of a muscle-specific Cas9 cassette together with single-guide RNA cassettes and, in one approach, a dystrophin homology region to fully correct the mutation...
February 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28195359/sodium-taurocholate-cotransporting-polypeptide-is-the-limiting-host-factor-of-hepatitis-b-virus-infection-in-macaque-and-pig-hepatocytes
#19
Florian A Lempp, Ellen Wiedtke, Bingqian Qu, Pierre Roques, Isabelle Chemin, Florian W R Vondran, Roger Le Grand, Dirk Grimm, Stephan Urban
: Infections with the human Hepatitis B (HBV) and Hepatitis D Virus (HDV) depend on species-specific host factors like the receptor human sodium taurocholate cotransporting polypeptide hNTCP. Complementation of mouse hepatocytes with hNTCP confers susceptibility to HDV but not HBV indicating the requirement of additional HBV-specific factors. As an essential premise towards the establishment for an HBV-susceptible animal model, we investigated the role of hNTCP as a limiting factor of hepatocytes in commonly used laboratory animals...
February 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28194746/stimuli-responsive-polymeric-nanocarriers-for-efficient-gene-delivery
#20
REVIEW
Yingqin Li, Jinbiao Gao, Chao Zhang, Zhong Cao, Du Cheng, Jie Liu, Xintao Shuai
Gene therapy provides an alternative and effective method for treatment of genetic diseases and cancers that are refractory to conventional therapeutics. The success of gene therapy is largely dependent on the development of safe and effective gene delivery vectors for transporting genetic material from the blood stream to the cytoplasm or nucleus. Current gene vectors can be divided into viral and non-viral vectors. Although non-viral gene delivery carriers can offer some advantages, such as safety and facile fabrication, they do not possess the same high gene transfection efficiency as viral vectors due to a lack of functionality to overcome extra- and intracellular gene delivery obstacles...
April 2017: Topics in Current Chemistry (Journal)
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