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https://www.readbyqxmd.com/read/27910061/inhaled-gene-transfer-for-pulmonary-circulation
#1
Jaume Aguero, Lahouaria Hadri, Nadjib Hammoudi, Lauren Leonardson, Roger J Hajjar, Kiyotake Ishikawa
Chronic pulmonary hypertension (PH) is associated with right ventricular failure and high mortality regardless of the underlying disease. Currently, therapies can improve clinical outcomes in specific subsets of patients, but have little impact on the progression of pulmonary vascular remodeling. Upon new advances in vector development and delivery techniques, gene therapy is a novel strategy in this field with the potential of overcoming the main limitations of approved drug therapies: modulation of novel anti-remodeling targets and selective pulmonary vasculature targeting with minimal systemic effects...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27910050/gene-transfer-to-rodent-hearts-in-vivo
#2
Federica Del Monte, Kiyotake Ishikawa, Roger J Hajjar
Altering expression of specific genes in rodent models allows the dissection of various pathways involved in various disease states. Advances in gene transfer technologies produced vectors with tissue specificity, various time courses, increasing or knocking down genes in an externally controlled fashion. To achieve this goal, appropriate vector delivery method is essential for successfully conducting experiments. In this chapter, we focus on cardiac gene transfer in rodents that can be employed for delivering both viral and nonviral vectors...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27910044/cell-based-measurement-of-neutralizing-antibodies-against-adeno-associated-virus-aav
#3
Andreas Jungmann, Oliver Müller, Kleopatra Rapti
In recent years gene therapy using adeno-associated viral (AAV) vectors to treat cardiac disease has seen an unprecedented surge, owing to its safety, low immunogenicity relative to other vectors and high and long-term transduction efficiency. This field has also been hampered by the presence of preexisting neutralizing antibodies, not only in patients participating in clinical trials but also in preclinical large animal models. These conflicting circumstances have generated the need for a simple, efficient, and fast assay to screen subjects for the presence of neutralizing antibodies, or lack thereof, in order for them to be included in gene therapy trials...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909702/complement-inhibition-enables-tumor-delivery-of-lcmv-glycoprotein-pseudotyped-viruses-in-the-presence-of-antiviral-antibodies
#4
Laura Evgin, Carolina S Ilkow, Marie-Claude Bourgeois-Daigneault, Christiano Tanese de Souza, Lawton Stubbert, Michael S Huh, Victoria A Jennings, Monique Marguerie, Sergio A Acuna, Brian A Keller, Charles Lefebvre, Theresa Falls, Fabrice Le Boeuf, Rebecca A Auer, John D Lambris, J Andrea McCart, David F Stojdl, John C Bell
The systemic delivery of therapeutic viruses, such as oncolytic viruses or vaccines, is limited by the generation of neutralizing antibodies. While pseudotyping of rhabdoviruses with the lymphocytic choriomeningitis virus glycoprotein has previously allowed for multiple rounds of delivery in mice, this strategy has not translated to other animal models. For the first time, we provide experimental evidence that antibodies generated against the lymphocytic choriomeningitis virus glycoprotein mediate robust complement-dependent viral neutralization via activation of the classical pathway...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27909699/aav-mediated-sirt1-overexpression-in-skeletal-muscle-activates-oxidative-capacity-but-does-not-prevent-insulin-resistance
#5
Laia Vilà, Carles Roca, Ivet Elias, Alba Casellas, Ricardo Lage, Sylvie Franckhauser, Fatima Bosch
Type 2 diabetes is characterized by triglyceride accumulation and reduced lipid oxidation capacity in skeletal muscle. SIRT1 is a key protein in the regulation of lipid oxidation and its expression is reduced in the skeletal muscle of insulin resistant mice. In this tissue, Sirt1 up-regulates the expression of genes involved in oxidative metabolism and improves mitochondrial function mainly through PPARGC1 deacetylation. Here we examined whether Sirt1 overexpression mediated by adeno-associated viral vectors of serotype 1 (AAV1) specifically in skeletal muscle can counteract the development of insulin resistance induced by a high fat diet in mice...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27908832/evaluation-of-two-strains-of-marek-s-disease-virus-serotype-1-for-the-development-of-recombinant-vaccines-against-very-virulent-infectious-bursal-disease-virus
#6
Kai Li, Yongzhen Liu, Changjun Liu, Li Gao, Yulong Gao, Yanping Zhang, Hongyu Cui, Xiaole Qi, Li Zhong, Xiaomei Wang
Attenuated strains of Marek's disease virus serotype 1 (MDV1), and the closely related herpesvirus of turkeys, are among the most potent vectors for development of recombinant vaccines for poultry. To investigate the effects of MDV1 strain characteristics on the protective efficacy of the recombinant vaccines, we developed two recombinant MDV1 vaccines for expressing the VP2 gene of infectious bursal disease virus (IBDV) based on two different MDV1 strains, the attenuated strain 814 and the Meq gene-deleted recombinant MDV1 strain rLMS△Meq, as the viral vectors...
November 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27906681/sirna-mediated-suppression-of-collagen-type-iv-alpha-2-col4a2-mrna-inhibits-triple-negative-breast-cancer-cell-proliferation-and-migration
#7
He Jing Song, Guan Hong, Jianbo Yang, Zheng Duo, Fu Li, Chen Wei Cai, Luo Xue Ying, Mao You Sheng, Ou Yang YiWen, Pan Yue, Chang Zou
Triple-negative breast cancer (TNBC) is more aggressive than other breast cancer subtypes. Collagen type IV alpha 2 (COL4A2), a major component of the basement membrane, dynamically influences a wide range of biological processes, including cancer pathogenesis and progression. This study evaluated the effects of COL4A2 siRNA delivered by lentiviral vector to TNBC cells. COL4A2 siRNA lenti-viral vector was constructed and transfected into MDA-MB-231 and MDA-MB-468 cells. The COL4A2 mRNA levels were quantified by RT-PCR...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27905841/cell-delivered-entry-inhibitors-for-hiv-1-ccr5-downregulation-and-blocking-virus-membrane-fusion-in-defending-the-host-cell-population
#8
Geoff Symonds, Jeffrey S Bartlett, Hans-Peter Kiem, Marlene Tsie, Louis Breton
HIV-1 infection requires the presence of the CD4 receptor on the target cell surface and a coreceptor, predominantly CC-chemokine receptor 5 (CCR5). It has been shown that individuals who are homozygous for a defective CCR5 gene are protected from HIV-1 infection. A novel self-inactivating lentiviral vector LVsh5/C46 (Cal-1) has been engineered to block HIV-1 infection with two viral entry inhibitors, conferring resistance to HIV-1 infection from both CCR5 and CXCR4 tropic strains. Cal-1 encodes a short hairpin RNA (sh5) to downregulate CCR5 and C46, an HIV-1 fusion inhibitor...
December 2016: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/27903748/hepatic-expression-of-adenovirus-36-e4orf1-improves-glycemic-control-and-promotes-glucose-metabolism-via-akt-activation
#9
Travis B McMurphy, Wei Huang, Run Xiao, Xianglan Liu, Nikhil V Dhurandhar, Lei Cao
Considering that impaired proximal insulin signaling is linked with diabetes, approaches that enhance glucose disposal independent of insulin signaling are attractive. In vitro data indicate that the E4ORF1 peptide derived from human adenovirus 36 (Ad36) interacts with cells from adipose tissue, skeletal muscle and liver to enhance glucose disposal, independent of proximal insulin signaling. Adipocyte-specific expression of Ad36E4ORF1 improved hyperglycemia in mice. To determine the hepatic interaction of Ad36E4ORF1 in enhancing glycemic control, we expressed E4ORF1 of Ad36 or adenovirus 5, or fluorescent tag alone using recombinant adeno-associated viral vector in the livers of three mouse models...
November 30, 2016: Diabetes
https://www.readbyqxmd.com/read/27903483/therapeutic-benefits-and-adverse-effects-of-combined-pro-angiogenic-gene-therapy-in-mouse-critical-leg-ischemia
#10
Benoît Lebas, Julien Galley, Edith Renaud-Gabardos, Françoise Pujol, Françoise Lenfant, Barbara Garmy-Susini, Xavier Chaufour, Anne-Catherine Prats
OBJECTIVE: Critical leg ischemia (CLI) represents the ultimate stage of peripheral arterial disease. Despite current surgery advances, patients with CLI have limited therapeutic options. Therapeutic angiogenesis thus appears as a powerful approach, aiming to stimulate vessel formation by angiogenic molecules administration. In this context, combined gene therapy has proved the most efficient. The present study aims to compare, in a preclinical mouse model, the therapeutic benefit of a combination of two angiogenic factors FGF2 (fibroblast growth factor 2) and Cyr61 using plasmid and viral vectors, able to generate short or long-term transgene expression in the leg, respectively...
November 26, 2016: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/27903326/characterizing-areas-of-potential-human-exposure-to-eastern-equine-encephalitis-virus-using-serological-and-clinical-data-from-horses
#11
J-P Rocheleau, J Arsenault, N H Ogden, L R Lindsay, M Drebot, P Michel
Eastern equine encephalitis (EEE) is a rare but severe emerging vector-borne disease affecting human and animal populations in the northeastern United States where it is endemic. Key knowledge gaps remain about the epidemiology of EEE virus (EEEV) in areas where its emergence has more recently been reported. In Eastern Canada, viral activity has been recorded in mosquitoes and horses throughout the 2000s but cases of EEEV in humans have not been reported so far. This study was designed to provide an assessment of possible EEEV human exposure by modelling environmental risk factors for EEEV in horses, identifying high-risk environments and mapping risk in the province of Quebec, Canada...
December 1, 2016: Epidemiology and Infection
https://www.readbyqxmd.com/read/27902403/the-non-canonical-tomato-yellow-leaf-curl-virus-recombinant-that-displaced-its-parental-viruses-in-southern-morocco-exhibits-a-high-selective-advantage-in-experimental-conditions
#12
Zineb Belabess, Michel Peterschmitt, Martine Granier, Abdessalem Tahiri, Abdelali Blenzar, Cica Urbino
Recombination events are frequently inferred from the increasing number of sequenced viral genomes, but their impact on natural viral populations has rarely been evidenced. TYLCV-IS76 is a recombinant (Begomovirus, Geminiviridae) between the Israel strain of Tomato yellow leaf curl virus (TYLCV-IL) and the Spanish strain of Tomato yellow leaf curl Sardinia virus (TYLCSV-ES) that was generated most probably in the late 1990s in Southern Morocco (Souss). Its emergence in the 2000s coincided with the increasing use of resistant tomato cultivars bearing the Ty-1 gene, and led eventually to the entire displacement of both parental viruses in the Souss...
October 14, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27902399/truncation-of-the-enzootic-nasal-tumor-virus-envelope-protein-cytoplasmic-tail-increases-env-mediated-fusion-and-infectivity
#13
Scott R Walsh, Jondavid G de Jong, Jacob P van Vloten, María Carla Rosales Gerpe, Lisa A Santry, Sarah K Wootton
Enzootic nasal tumor virus (ENTV) and Jaagsiekte sheep retrovirus (JSRV) are highly related ovine betaretroviruses that induce nasal and lung tumors in small ruminants, respectively. While the ENTV and JSRV envelope (Env) glycoproteins mediate virus entry using the same cellular receptor, the GPI-linked protein hyaluronoglucosaminidase, ENTV Env pseudovirions mediate entry into cells from a much more restricted range of species than do JSRV Env pseudovirions. Unlike JSRV Env, ENTV Env does not induce cell fusion at pH 5...
November 11, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27899444/antigen-dependent-competition-shapes-the-local-repertoire-of-tissue-resident-memory-cd8-t-cells
#14
Andreas Muschaweckh, Veit R Buchholz, Anne Fellenzer, Christian Hessel, Paul-Albert König, Sha Tao, Ronny Tao, Mathias Heikenwälder, Dirk H Busch, Thomas Korn, Wolfgang Kastenmüller, Ingo Drexler, Georg Gasteiger
Tissue-resident memory CD8(+) T cells (TRM) constitute a major component of the immune-surveillance system in nonlymphoid organs. Local, noncognate factors are both necessary and sufficient to support the programming of TRM cell fate in tissue-infiltrating T cells. Recent evidence suggests that TCR signals received in infected nonlymphoid tissues additionally contribute to TRM cell formation. Here, we asked how antigen-dependent pathways influence the generation of skin-resident memory T cells that arise from a polyclonal repertoire of cells induced by infection with an antigenically complex virus and recombinant vaccine vector...
November 29, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27899228/the-recombinant-n-terminal-domain-of-spike-proteins-is-a-potential-vaccine-against-middle-east-respiratory-syndrome-coronavirus-mers-cov-infection
#15
Lan Jiaming, Yao Yanfeng, Deng Yao, Hu Yawei, Bao Linlin, Huang Baoying, Yan Jinghua, George F Gao, Qin Chuan, Tan Wenjie
The persistent public health threat of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the need for an effective MERS-CoV vaccine. Previous studies have focused mainly on the receptor-binding domain (RBD) on the spike protein of MERS-CoV. Herein, we investigated the immunogenicity and protective potential of the recombinant N-terminal domain (rNTD) of spike proteins as a vaccine candidate. BALB/c mice vaccinated with 5 or 10μg of rNTD protein demonstrated a significant humoral immune response (serum IgG and neutralizing activity)...
November 26, 2016: Vaccine
https://www.readbyqxmd.com/read/27893183/toxic-effects-of-human-and-rodent-variants-of-alpha-synuclein-in-vivo
#16
Natalie Landeck, Kerstin Buck, Deniz Kirik
In Parkinson's disease, abnormal alpha-synuclein (asyn) accumulation leads to the formation of soluble oligomeric species thought to be toxic to cells as well as intraneuronal inclusions. To date, the precise mechanisms leading to aggregation of asyn in the brain is not well understood. Previous studies in yeast, drosophila and transgenic mice suggested that a non-A beta component depleted version of human asyn [h-asyn(D70-83)] or human beta-synuclein (h-bsyn), naturally lacking this centrally located hydrophobic region, are less prone to form aggregates in vitro and are expected to be less toxic compared to h-asyn in vivo, although not all experimental studies unequivocally support the latter view...
November 28, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27892499/recognition-of-extremophilic-archaeal-viruses-by-eukaryotic-cells-a-promising-nanoplatform-from-the-third-domain-of-life
#17
Kristine Buch Uldahl, Linping Wu, Arnaldur Hall, Pavlos Papathanasiou, Xu Peng, Seyed Moein Moghimi
Viruses from the third domain of life, Archaea, exhibit unusual features including extreme stability that allow their survival in harsh environments. In addition, these species have never been reported to integrate into human or any other eukaryotic genomes, and could thus serve for exploration of novel medical nanoplatforms. Here, we selected two archaeal viruses Sulfolobus monocaudavirus 1 (SMV1) and Sulfolobus spindle shaped virus 2 (SSV2) owing to their unique spindle shape, hyperthermostable and acid-resistant nature and studied their interaction with mammalian cells...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27891076/recombinant-adeno-associated-virus-serotype-6-raav6-potently-and-preferentially-transduces-rat-astrocytes-in-vitro-and-in-vivo
#18
Alexandra L Schober, Dmitriy A Gagarkin, Ying Chen, Guangping Gao, Lauren Jacobson, Alexander A Mongin
Recombinant adeno-associated virus vectors are an increasingly popular tool for gene delivery to the CNS because of their non-pathological nature, low immunogenicity, and ability to stably transduce dividing and non-dividing cells. One of the limitations of rAAVs is their preferential tropism for neuronal cells. Glial cells, specifically astrocytes, appear to be infected at low rates. To overcome this limitation, previous studies utilized rAAVs with astrocyte-specific promoters or assorted rAAV serotypes and pseudotypes with purported selectivity for astrocytes...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27890448/vaccines-against-pseudorabies-virus-prv
#19
C M Freuling, T F Müller, T C Mettenleiter
Aujeszkýs disease (AD, pseudorabies) is a notifiable herpesvirus infection of pigs causing substantial economic losses to swine producers. AD in pigs is controlled by the use of vaccination with inactivated and attenuated live vaccines. Starting with classically attenuated live vaccines derived from low virulent field isolates, AD vaccination has pioneered novel strategies in animal disease control by the first use of genetically engineered live virus vaccines lacking virulence-determining genes, and the concept of DIVA, i...
November 18, 2016: Veterinary Microbiology
https://www.readbyqxmd.com/read/27889981/chimeric-trojan-protein-insertion-in-lentiviral-membranes-makes-lentiviruses-susceptible-to-neutralisation-by-anti-tetanus-serum-antibodies
#20
Anita Le-Heron, Steve Patterson, Rafael J Yáñez-Muñoz, George Dickson
This study describes the initial testing of a novel strategy for neutralisation of lentiviruses using the fundamental biology of enveloped viruses' assembly and budding. In the field of gene therapy, viral vector surface proteins have been manipulated in order to redirect host cell specificity by alteration of pseudo-types. We tested whether known viral pseudo-typing proteins or surface proteins known to be recruited to the HIV envelope could be engineered to carry neutralising epitopes from another microorganism onto the lentiviral surface...
November 27, 2016: Human Gene Therapy
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