Mycoplasma hyopneumoniae causes severe economic losses to the swine industry worldwide and the prevention of its related disease, enzootic porcine pneumonia, remains a challenge. The P97 adhesin protein of M. hyopneumoniae should be a good candidate for the development of a subunit vaccine because antibodies produced against P97 could prevent the adhesion of the pathogen to the respiratory epithelial cells in vitro. In the present study, a P97 recombinant replication-defective adenovirus (rAdP97c) subunit vaccine efficiency was evaluated in pigs. The rAdP97c vaccine was found to induce both strong P97 specific humoral and cellular immune responses. The rAdP97c vaccinated pigs developed a lower amount of macroscopic lung lesions (18.5 ± 9.6%) compared to the unvaccinated and challenged animals (45.8 ± 11.5%). rAdP97c vaccine reduced significantly the severity of inflammatory response and the amount of M. hyopneumoniae in the respiratory tract. Furthermore, the average daily weight gain was ...

Hong Kong Med J 2009;15(Suppl 2):S33-6 Mouse studies of SARS coronavirus-specific immune responses to recombinant replication-defective adenovirus expressing SARS coronavirus N protein FWY Sin, SCS Ch

In vivo gene transfer and expression in normal uninjured blood vessels using replication-deficient recombinant adenovirus vectors Academic Article ...

TY - JOUR. T1 - Enhancement of in vivo adenovirus-mediated gene transfer and expression by prior depletion of tissue macrophages in the target organ. AU - Wolff, Gerhard. AU - Worgall, Stefan. AU - Van Rooijen, Nico. AU - Song, Wen Ru. AU - Harvey, Ben Gary. AU - Crystal, Ronald G.. PY - 1997/1/1. Y1 - 1997/1/1. N2 - Based on the hypothesis that tissue macrophages present an obstacle for adenovirus (Ad) vector-mediated gene transfer to internal organs, this study evaluated the consequences of transient depletion of Kupffer cells on subsequent transfer of the Ad vector genome and Ad vector-directed gene expression in the livers of experimental animals. Depletion of Kupffer cells in mice by intravenous administration of multilamellar liposomes containing dichloromethylene-bisphosphonate permitted subsequent intravenous administration of an Ad vector to provide a higher input of recombinant adenoviral DNA to the liver, an absolute increase in transgene expression, and a delayed clearance of the ...

TY - JOUR. T1 - Potential of the conditionally replicative adenovirus Ad5-Delta24RGD in the treatment of malignant gliomas and its enhanced effect with radiotherapy. AU - Lamfers, Martine L M. AU - Grill, Jacques. AU - Dirven, Clemens M F. AU - Van Beusechem, Victor W. AU - Geoerger, Birgit. AU - Van Den Berg, Jaap. AU - Alemany, Ramon. AU - Fueyo, Juan. AU - Curiel, David T. AU - Vassal, Gilles. AU - Pinedo, Herbert M. AU - Vandertop, W Peter. AU - Gerritsen, Winald R. PY - 2002/10/15. Y1 - 2002/10/15. N2 - The use of replication-competent adenoviruses (Ads) for cancer therapy is receiving widespread attention, especially for the treatment of tumors refractory to current treatments such as glioblastoma. AdDelta24, which carries a 24-bp deletion in E1A and replicates in cells with a retinoblastoma-defective pathway, produced a strong antitumor effect in glioma. To improve infection efficiency of primary glioma cells, which express low levels of coxsackie adenovirus receptor (CAR), the tropism of ...

TY - JOUR. T1 - Inhibition of repair of radiation-induced DNA damage enhances gene expression from replication-defective adenoviral vectors. AU - Hingorani, Mohan. AU - White, Christine L.. AU - Merron, Andrew. AU - Peerlinck, Inge. AU - Gore, Martin E.. AU - Slade, Andrew. AU - Scott, Simon D.. AU - Nutting, Christopher M.. AU - Pandha, Hardev S.. AU - Melcher, Alan A.. AU - Vile, Richard Geoffrey. AU - Vassaux, Georges. AU - Harrington, Kevin J.. PY - 2008/12/1. Y1 - 2008/12/1. N2 - Radiation has been shown to up-regulate gene expression from adenoviral vectors in previous studies. In the current study, we show that radiation-induced dsDNA breaks and subsequent signaling through the mitogen-activated protein kinase (MAPK) pathway are responsible, at least in part, for this enhancement of transgene expression both in vitro and in vivo. Inhibitors of ataxia-telangiectasia-mutated, poly(ADP-ribose) polymerase-mutated, and DNA-dependent protein kinase (DNA-PK)-mediated DNA repair were shown to ...

Staining for LacZ 5 days after intraocular injection of AdLacZ.10 in adult wild-type mice and at various times after injection in transgenic mice with increased expression of PDGF in the retina. Mice were given an intravitreous injection of 5 × 108 (A-E, J-P) or a subretinal injection of 107 (F-I) AdLacZ.10 particles. After 5 days, or as otherwise indicated, ocular sections and retinal and choroidal wholemounts were stained for LacZ. (A) Albino BALB/c mice showed staining in the corneal endothelium, the trabecular meshwork, the iris pigmented epithelium, and the ciliary body (bar, 200 μm). (B) Flatmounts of iris from albino BALB/c mice showed diffuse dark staining throughout the entire iris. (C.) Retinal wholemounts from adult C57BL/6 mice showed scattered focal staining throughout the retina, with more intense staining at the optic nerve. (D, E) Ocular sections from adult C57BL/6 mice showed prominent staining in and around the optic nerve and focal staining of cells in the inner nuclear ...

Title: Recent Advances in Adenovirus-mediated Gene Therapy for Cerebral Ischemia. VOLUME: 3 ISSUE: 1. Author(s):Makoto Masumura and Ryuji Hata. Affiliation:Suntory Biomedical Research Limited, 1-1-1, Wakayama-dai, Shimamoto-cho, Mishima-gun, Osaka 618- 8503, Japan. Keywords:cerebral ischemia, cerebral infarction, gene therapy, adenovirus vector. Abstract: Cerebral ischemia induces many degenerative cellular reactions, including the release of excitatory amino acids, the formation of oxygen free radicals, Ca2+ overload, the activation of several cellular enzyme systems such as Ca2+ dependent proteases, and the initiation of genomic responses that can affect the tissue outside the area of reduced blood flow. Furthermore, increasing evidence indicates that apoptosis contributes to the death of brain cells following cerebral ischemia. Several studies have shown that cerebral ischemia alters the expression of genes, some of which may play protective or harmful roles. Although many genes have the ...

TY - JOUR. T1 - In vivo studies of adenovirus-based p53 gene therapy for ovarian cancer. AU - Von Gruenigen, Vivian E.. AU - Santoso, Joseph T.. AU - Coleman, Robert L.. AU - Muller, Carolyn Y.. AU - Miller, David Scott. AU - Mathis, J. Michael. PY - 1998/6. Y1 - 1998/6. N2 - Objectives. To test the safety, efficacy, and toxicity of gene therapy using wild-type p53-expressing adenovirus (Ad-CMV-p53) in a nude mouse model with intraperitoneal (ip) 2774 human ovarian cancer cell line that contains a p53 mutation. Study design. An initial study of adenovirus tolerance was determined in nude mice by a single ip injection of increasing doses of Ad- CMV-p53. Nude mice were implanted with an LD100 dose of 1 x 107 cells. To study the efficacy and specificity of Ad-CMV-p53 treatment, the mice received treatment with different adenovirus constructs. One group received Ad-CMV- p53 and another group received a control adenovirus construct, Ad-CMV-βgal. To study the treatment response to Ad-CMV-p53, the ...

Purification of recombinant adenovirus type 3 dodecahedric virus-like particles for biomedical applications using short monolithic columns

PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.

Yang et al identified miR-206 in a microarray screen for upregulated miRNAs in neonatal rat cardiomyocytes overexpressing Yap. Previously, miR-206 had been shown to play an important role in skeletal muscle hypertrophy.11 Yang et al performed a series of in vitro experiments that led them to conclude that the Hippo/Yap pathway regulates cardiomyocyte hypertrophy and survival through the actions of miR-206. Adenoviral-mediated overexpression of Yap in neonatal rat cardiomyocytes led to increased miR-206 expression, whereas overexpression of Mst1, a critical kinase in the Hippo pathway, led to decreased miR-206 expression. To draw a functional connection between Yap and miR-206, the authors show that adenoviral-mediated overexpression of miR-206 or Yap in neonatal rat cardiomyocytes produced similar changes in cardiomyocyte hypertrophy and cell viability after treatment with the apoptosis inducer chelerythrine. Combined loss of miR-206 and overexpression of Yap in vitro abrogated the phenotypic ...

Vaccines that have benefited from the use of adjuvants span multiple classes, such as subunit vaccines, vaccines employing viral vectors and DNA vaccines. For example, the addition of adjuvants to administered peptide antigens such as gp120 can augment immune activity in vivo, resulting in durable responses postvaccination [49]. The use of viral vectors as a means of delivering an antigen of interest for vaccination continues to have wide popularity both in academia [50-53] as well as industry [54-56]. Employing viruses such as Modified Vaccinia Virus Ankara (MVA) allows for delivery of antigens into the cytoplasm of target cells, thus providing expression through MHC Class I and subsequent generation of CTL responses [57,58]. In addition to MVA, recombinant adenoviruses are being employed more often as viral vectors in vaccination [51,52,54-57]. While there are a number of adenovirus serotypes, recombinant replication-defective adenovirus serotype 5 (rAd5) is the most commonly employed variant ...

We developed a murine model of arterial gene transfer and used it to test the role of antigen-specific immunity in the loss of adenovirus-mediated transgene expression. Adenoviral vectors encoding either beta-galactosidase (beta-gal) or green fluorescent protein were infused to the lumen of normal common carotids of CD-1 and C57BL/6 mice and atherosclerotic carotids of Apoe(-/-) mice. At 3 days after gene transfer, significant reporter gene expression was detected in all strains. Transgene expression was transient, with expression undetectable at 14 days. Next, a beta-gal-expressing vector was infused into carotids of ROSA26 mice (transgenic for, and therefore tolerant of, beta-gal) and RAG-2(-/-) mice (deficient in recombinase-activating gene [RAG]-2 and therefore lacking in antigen-specific immunity). beta-Gal expression was again high at 3 days but declined substantially (|90%) by 14 days. In vivo labeling with bromodeoxyuridine revealed that carotid endothelial proliferation was in

The majority of breast cancers are oestrogen dependent and although current treatment strategies have improved, approximately 50% of the patients will develop metastasis. New treatments that result in long-term systemic immunity are therefore being developed. We have previously shown that adenoviral gene transfer of B7-I/IL-2 to murine breast cancer induces a high rate of complete turnout regression and systemic immunity. Since oestrogens not only affect breast cancer but also have been shown to modulate immune function and secretion of immune-regulatory cytokines, we explored whether administration of oestradiol altered the immune response induced by an adenoviral vector expressing B7-I/IL-2. An oestrogen-dependent murine breast cancer tumour was used in ovariectomised mice, supplemented either oestradiol or placebo. We report the somewhat unexpected finding that intratumoral injection of adenovirus expressing B7-I/IL-2 induces complete turnout regression in 76% of oestradiol-supplemented mice, ...

101F6 is a candidate tumor suppressor gene harbored on chromosome 3p21.3, a region with frequent and early allele loss and genetic alterations in many human cancers. We previously showed that enforced expression of wild-type 101F6 by adenoviral vector-mediated gene transfer significantly inhibited t …

Greig, JA, McVey, JH, Waddington, SN, Parker, AL, Buckley, SMK, Havenga, MJE, Nicklin, SA and Baker, AH (2008) Factor X enhances binding and transduction of human cancer cell lines by adenovirus (Ad) serotype 5 vectors but not by Ad35 In: 5th Annual Conference of the British-Society-for-Gene-Therapy, 2008-04-07 - 2008-04-09, Edinburgh, SCOTLAND. Full text not available from this repository ...

TY - JOUR. T1 - Reversal of potassium channel deficiency in cells from failing hearts by adenoviral gene transfer. T2 - A prototype for gene therapy for disorders of cardiac excitability and contractility. AU - Nuss, H. B.. AU - Johns, D. C.. AU - Kääb, S.. AU - Tomaselli, G. F.. AU - Kass, David A. AU - Lawrence, J. H.. AU - Marban, E.. PY - 1996. Y1 - 1996. N2 - Heart failure is a common, often lethal disorder in which conventional pharmacologic strategies have achieved limited success. Failing hearts exhibit a delay of electrical repolarization which predisposes to fatal arrhythmias. To explore the feasibility of gene therapy for this condition, we isolated myocytes from normal and failing dog hearts and quantified electrophysiologic and contractile parameters in primary culture. Action potentials were prolonged in failing cells as a result of diminished potassium currents. Exposure to AdShK, an adenovirus that overexpresses potassium channels, reversed the action potential prolongation of ...

The information presented here serves as a brief introduction to adenovirus, recombinant adenovirus, and their advantages over alternative viral vectors.

Yamaguchi, T., Kawabata, K., Kouyama, E., Ishii, K. J., Katayama, K., Suzuki, T., Kurachi, S., Sakurai, F., Akira, S., and Mizuguchi, H. Induction of type I interferon by adenovirus-encoded small RNAs. Proc. Natl. Acad. Sci. USA, 107, 17286-17291 (2010). Sakurai, F., Nakashima, K., Yamaguchi, T., Ichinose, T., Kawabata, K., Hayakawa, T., and Mizuguchi, H. Adenovirus serotype 35 vector-induced innate immune responses in dendritic cells derived from wild-type and human CD46-transgenic mice: Comparison with a fiber-substituted Ad vector containing fiber proteins of Ad serotype 35. J. Control. Rel., 148, 212-218 (2010). Tashiro K., Kawabata K., Inamura M., Takayama K., Furukawa N., Sakurai F., Katayama K., Hayakawa H., Furue-Kusuda M., Mizuguchi H., Adenovirus vector-mediated efficient transduction into human embryonic and induced pluripotent stem cells. Cell Reprogram., 12, 501-507 (2010). Eto Y., Yoshioka Y., Ishida T., Yao X., Morishige T., Narimatsu S., Mizuguchi H., Mukai Y., Okada N., Kiwada ...

Adenoviral System, Tet-On 3G Inducible. Very tight control of gene expression combined with the most advanced adenoviral gene delivery technology. cloning is even simpler than standard plasmid cloning.

Adenoviral System, Tet-On 3G Inducible. Very tight control of gene expression combined with the most advanced adenoviral gene delivery technology. cloning is even simpler than standard plasmid cloning.

Adenoviruses commonly infect humans, causing colds, flu-like symptoms and sometimes even death, but now UC San Francisco researchers have discovered that a new species of adenovirus can spread from primate to primate, and ...

OBJECTIVE: To construct an antisense RNA recombinant adenovirus vector of the human PDE5A1 promoter gene.. METHODS: A cDNA fragment containing the human PDE5A1 promoter and the human PDE5A1-specific exon was determined according to the gene bank. The antisense RNA fragment was synthesized artificially and subcloned into the pENTR. Then, the sequence of pENTR fragment was detected, and the recombinant adenovirus vector pAd/CMV/V5/antisense-PDE5A1 was constructed by LR reaction with the Gateway expression system. The identified recombinant adenovirus plasmid was digested with Pac I and transformed into 293A cells to package recombinant adenovirus particles. The recombinant adenovirus particles were tested with PCR technique and purified after acquisition by CsCl density gradient ultracentrifugation.. RESULTS: The sequencing result showed a 145 bp fragment in pENTR, which was proved to be the domain of the antisense RNA fragment. PCR confirmed that the antisense RNA fragment was cloned into the ...

TY - JOUR. T1 - Combination gene therapy with adenoviral vector-mediated HSV-tk + GCV and IL-12 in an orthotopic mouse model for prostate cancer. AU - Nasu, Y.. AU - Bangma, C. H.. AU - Hull, G. W.. AU - Yang, G.. AU - Wang, J.. AU - Shimura, S.. AU - Mccurdy, M. A.. AU - Ebara, S.. AU - Lee, H. M.. AU - Timme, T. L.. AU - Thompson, T. C.. N1 - Funding Information: This work was supported by grants from CaP CURE and NIH (CA68814 and SPORE P50-58204). We are most grateful to Drs Frank L Graham and Jack Gauldie for providing AdmIL-12 virus stock.. PY - 2001. Y1 - 2001. N2 - We previously demonstrated significant therapeutic activities associated with adenoviral vector-mediated Herpes Simplex Virus/thymidine kinase (AdHSV-tk) with ganciclovir (GCV) in situ gene therapy in the RM-1 orthotopic mouse prostate cancer model and interleukin-12 (AdmIL-12) in situ gene therapy in the RM-9 orthotopic mouse prostate model for prostate cancer. In both protocols, local cytotoxicity and activities against ...

TY - JOUR. T1 - Retrograde transfer of replication deficient recombinant adenovirus vector in the central nervous system for tracing studies. AU - Kuo, Hui. AU - Ingram, Donald K.. AU - Crystal, Ronald. AU - Mastrangeli, Andrea. PY - 1995/12/24. Y1 - 1995/12/24. N2 - We assessed the application of a replication deficient recombinant adenovirus vector as a retrograde tracer in neural pathway studies. The adenovirus vector, Ad.RSVBgal, containing the intracellular marker gene, β-galactosidase, was injected directly into the laterodorsal striatum of rats. The retrograde transport of the vector from the injection site was clearly visible in the cerebral cortex, thalamic nucleus, and substantia nigra. No evidence for anterograde transport of the vector was found. When the vector was injected into the genu of the corpus callosum, little uptake of the vector by fibers was noted which suggested that uptake by fibers-of-passage should not be a problem in tracing studies. The present study demonstrates ...

Title: Transductional Targeting with Recombinant Adenovirus Vectors. VOLUME: 2 ISSUE: 3. Author(s):Valerie Legrand, Philippe Leissner, Arend Winter, Majid Mehtali and Monika Lusky. Affiliation:CAREXS.A., 11 rue Humann, 67000 Strasbourg, France. Keywords:Adenovirus Vectors, TROPISM, Fiber Protein, Monoclonal antibody. Abstract: Replication-deficient adenoviruses are considered as gene delivery vectors for the genetic treatment of a variety of diseases. The ability of such vectors to mediate efficient expression of therapeutic genes in a broad spectrum of dividing and non-dividing cell types constitutes an advantage over alternative gene transfer vectors. However, this broad tissue tropism may also turn disadvantageous when genes encoding potentially harmful proteins (e.g. cytokines, toxic proteins) are expressed in surrounding normal tissues. Therefore, specific restrictions of the viral tropism would represent a significant technological advance towards safer and more efficient gene delivery ...

OBJECTIVES To investigate the validity of catalase recombinant adenovirus on the treatment of oxidative cataract. METHODS The coding sequence of catalase was cloned and the catalase recombinant adenovirus was constructed. The expression time course of catalase gene in rat lens infected by recombinant adenovirus was determined by Western blotting. Cultured rat lens were randomly divided into 3 groups: the control group, the group treated by hydrogen peroxide and the group treated by hydrogen peroxide combined with catalase recombinant adenovirus. The transparence and apoptosis ratio of lens on the time points of 6, 12, 18, 24 hours were determined by image analysis and double colour flowcytometry. RESULTS The coding sequence of catalase was cloned and recombinant adenovirus was successfully constructed. The expression of catalase in cultured rat lens infected by recombinant adenovirus reached peak point on 9 hours post infection and maintained the level in the whole experiment period. The

Improvement of transduction and augmentation of cytotoxicity are crucial for adenoviruses (Ad)-mediated gene therapy for cancer. Down-regulated expression of type 5 Ad (Ad5) receptors on human tumors hampered Ad-mediated transduction. Furthermore, a role of the p53 pathways in cytotoxicity mediated by replication-competent Ad remained uncharacterized. We constructed replication-competent Ad5 of which the E1 region genes were activated by a transcriptional regulatory region of the midkine or the survivin gene, which is expressed preferentially in human tumors. We also prepared replication-competent Ad5 which were regulated by the same region but had a fiber-knob region derived from serotype 35 (AdF35). We examined the cytotoxicity of these Ad and a possible combinatory use of the replication-competent AdF35 and Ad5 expressing the wild-type p53 gene (Ad5/p53) in esophageal carcinoma cells. Expression levels of molecules involved in cell death, anti-tumor effects in vivo and production of viral progenies

Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor involved in differentiation, survival and activation of myeloid and non-myeloid cells with important implications for lung antibacterial immunity. Here we examined the effect of pulmonary adenoviral vector-mediated delivery of GM-CSF (AdGM-CSF) on anti-mycobacterial immunity in M. bovis BCG infected mice. Exposure of M. bovis BCG infected mice to AdGM-CSF either applied on 6h, or 6h and 7days post-infection substantially increased alveolar recruitment of iNOS and IL-12 expressing macrophages, and significantly increased accumulation of IFNγpos T cells and particularly regulatory T cells (Tregs). This was accompanied by significantly reduced mycobacterial loads in the lungs of mice. Importantly, diphtheria toxin-induced depletion of Tregs did not influence mycobacterial loads, but accentuated immunopathology in AdGM-CSF-exposed mice infected with M. bovis BCG. Together, the data demonstrate that AdGM-CSF ...

TY - JOUR. T1 - Postischemic gene transfer of midkine, a neurotrophic factor, protects against focal brain ischemia. AU - Takada, J.. AU - Ooboshi, H.. AU - Ago, T.. AU - Kitazono, T.. AU - Yao, H.. AU - Kadomatsu, K.. AU - Muramatsu, T.. AU - Ibayashi, S.. AU - Iida, M.. PY - 2005/3/1. Y1 - 2005/3/1. N2 - Gene therapy may be a promising approach for treatment of brain ischemia. In this study, we examined the effect of postischemic gene transfer of midkine, a heparin-binding neurotrophic factor, using a focal brain ischemia model with the photothrombotic occlusion method. At 90 min after induction of brain ischemia in spontaneously hypertensive rats, a replication-deficient recombinant adenovirus encoding mouse midkine (AdMK, n = 7) or a control vector encoding β-galactosidase (Adβgal, n = 7) was injected into the lateral ventricle ipsilateral to ischemia. At 2 days after ischemia, we determined infarct volume by 2,3,5-triphenyltetrazolium chloride staining. There were no significant ...

Control of the HIV pandemic can only be achieved with the development of a safe and effective preventive HIV vaccine. A vaccine that will prevent HIV infection will elicit a strong immune response from both CD4 and CD8 cells. Recombinant adenovirus serotype vectors have been shown to elicit just such a response. The purpose of this study is to determine the safety and immunogenicity of the recombinant adenovirus serotype 5 preventive HIV-1 vaccine.. This study will last 18 to 24 months. Participants will be randomly assigned to one of four arms that will receive vaccine or placebo administered via intramuscular injection. Participants in Arms 1, 2, and 3 will all receive 3 injections. Participants in Arm 4 will receive one injection. For most participants, there will be 10 study visits in this study; for participants in Arm 4, there will be only 7 visits. For Arms 1, 2, and 3, study visits will occur at baseline and on Days 0, 14, 28, 42, 56, 168, 182,196, and 365. Participants in Arms 1, 2, and ...

Adenoviral Vectors for Gene treatment, moment Edition offers special, entire assurance of the gene supply cars which are in line with the adenovirus thats rising as an immense instrument in gene remedy. those fascinating new healing brokers have nice capability for the therapy of illness, making gene remedy a fast-growing box for learn. This ebook provides themes starting from the fundamental biology of adenoviruses, during the building and purification of adenoviral vectors, state-of-the-art vectorology, and using adenoviral vectors in preclinical animal types, with ultimate attention of the regulatory concerns surrounding human medical gene remedy trials. This extensive scope of knowledge offers a superb evaluate of the sector, permitting the reader to achieve an entire figuring out of the advance and use of adenoviral vectors.. ...

Intraperitoneal (i.p.) recurrence of cisplatin-refractory and p53 mutant ovarian cancer is a major clinical problem, despite surgery and chemotherapy. dl1520 (ONYX-015) is an E1B-55 kDa gene-deleted adenovirus engineered selectively to replicate in and destroy cancer cells lacking functional p53. Ho …

Recombinant adenovirus vectors are promising, highly characterized platforms from which novel vaccines can be produced. Conventional Ad5[E1−] vaccines possess the ability to promote strong immunologic responses against their expressed transgenes, but the same properties also trigger host antiviral responses, which can lead to increased toxicity, limited persistence, and decreased efficacy in the face of preexisting anti-Ad5 immunity (7, 28, 29, 34, 46). Alternatively, multiply deleted Ad5[E1−,E2b−] vaccines have been found to overcome several of these obstacles. Head-to-head comparisons of traditional Ad5[E1−] vaccines and E2b gene-deleted, Ad5[E1−,E2b−] vaccines have shown that the latter produce virtually no hepatotoxicity after systemic administration (29), persist and express transgenes for longer durations than Ad5[E1−] vaccines (28, 34), and remain therapeutically efficacious in hosts harboring substantial preexisting anti-Ad5 immunity (5, 14-16, 30).. It has been largely ...

TY - JOUR. T1 - An effective gene-knockdown using multiple shRNA-expressing adenovirus vectors. AU - Motegi, Yukari. AU - Katayama, Kazufumi. AU - Sakurai, Fuminori. AU - Kato, Takuya. AU - Yamaguchi, Tomoko. AU - Matsui, Hayato. AU - Takahashi, Masahide. AU - Kawabata, Kenji. AU - Mizuguchi, Hiroyuki. PY - 2011/7/30. Y1 - 2011/7/30. N2 - Viral vectors expressing short hairpin RNA (shRNA) are attractive for efficient and tissue-specific RNA interference (RNAi) delivery. We and others previously reported that recombinant adenovirus (Ad) vector-mediated RNAi has great potential for a variety of applications in molecular biology studies and gene therapy. In the present study, we have developed an efficient Ad vector-mediated RNAi system, in which an Ad vector carries four shRNA-expression cassettes (Ad-multi-shRNA vector), a simple and effective strategy for enhancing the RNAi response per Ad vector particle. The data demonstrated that the Ad-multi-shRNA vectors showed an enhanced RNAi effect ...

Recombinant adenoviruses currently are used for a variety of purposes, including gene transfer in vitro, vaccination in vivo, and gene therapy (1-4). Several features of adenovirus biology have made such viruses the vectors of choice for certain of these applications. For example, adenoviruses transfer genes to a broad spectrum of cell types, and gene transfer is not dependent on active cell division. Additionally, high titers of viruses and high levels of transgene expression generally can be obtained.. Decades of study of adenovirus biology have resulted in a detailed picture of the viral life cycle and the functions of the majority of viral proteins (5, 6). The genome of the most commonly used human adenovirus (serotype 5) consists of a linear, 36-kb, double-stranded DNA molecule. Both strands are transcribed and nearly all transcripts are heavily spliced. Viral transcription units are conventionally referred to as early (E1, E2, E3, and E4) and late, depending on their temporal expression ...

The plasminogen activation (PA) system is involved in vascular remodelling. Modulating its activity in vascular cells might be a way to interfere in processes such as angiogenesis and restenosis. Adenoviral vectors have become a favourable tool for direct gene transfer into vascular cells. In the interest of using adenoviral vectors to modulate plasminogen activator activity and endothelial and smooth muscle cell migration, we studied the effects of endothelial and smooth muscle cell transduction in vitro and in the umbilical vein ex vivo with a replication-defective adenoviral vector containing the β-galactosidase gene (AdCMVLacZ). Segments of the umbilical vein were infected with AdCMVLacZ (109-1010 pfu/ml). After 48 h strong β-galactosidase expression could be observed in the vessel wall, which was restricted to the endothelial layer. Although some heterogeneity in the transduction throughout the vessel could be seen, β-galactosidase expression was detectable for 21 days in explant. ...

A recombinant nucleic acid used for the production of a defective adenovirus containing an inserted sequence coding for a cytokine under the control of a promoter in the genomic sequence of the recombinant adenovirus. This recombinant adenovirus is useful in the preparation of anti-tumoral drugs which can be directly injected into the tumor of the host.

A simplified Ebola vaccine that consists of a modified GP protein (which is well-tolerated by human cells even at high concentrations) in a replication-defective adenoviral vector protects macaques.

La terapia génica consiste en la manipulación y utilización de material genético para el tratamiento de patologías. No obstante, esta estrategia requiere el uso de vectores de terapia génica para transportar el material genético al tejido diana de forma eficiente. Los vectores de terapia génica más comunes son los basados en el adenovirus humano de serotipo 5 (Ad5), porque, respecto a otros serotipos, el Ad5 tiene como ventaja su bioseguridad y facilidad de producción. Sin embargo, para que una célula sea transducida por el Ad5 ha de expresar un receptor reconocible por el Ad5, principalmente la proteína CAR, al que se une a través de su proteína fiber. El fiber de otros serotipos de adenovirus se une a receptores diferentes, permitiendo así la transducción de tipos celulares alternativos a los transducidos por el Ad5. De esta manera, una de las estrategias utilizadas para obtener un vector Ad5 con el tropismo de un serotipo diferente, es la pseudotipación del adenovirus, que ...

TY - JOUR. T1 - An altered subunit configuration associated with the actively transcribed DNA of integrated adenovirus genes. AU - Flint, S. J.. AU - Weintraub, Harold M.. PY - 1977/11. Y1 - 1977/11. N2 - The sensitivity to deoxyribonuclease I (DNAase I) of integrated adenovirus genes that encode mRNA has been compared to the sensitivity of adjacent viral DNA sequences that are not expressed as mRNA in two lines of adenovirus type 5-transformed hamster cells. We determined the concentrations of integrated DNA sequences homologous to different regions of the viral genome before and after mild DNAase I digestion of intact nuclei by measuring the rate of reassociation of restriction endonuclease fragments of labeled adenovirus DNA in the presence of DNA isolated from untreated and digested transformed cell nuclei. The HT14A cell line contains 2.4 copies of the left-hand 35% of the adenovirus type 5 genome per diploid quantity of cell DNA. Integrated sequences that are preferentially sensitive to ...

Wild-type p53 is involved in several aspects of cell cycle control and suppression of transformation, inducing either apoptosis or G1 block in cell cycle progression. Using a recombinant adenovirus containing the wild-type p53 cDNA, the biological effects of the newly expressed wild-type p53 protein were examined in six human glioma cell lines. Three cell lines (U-251 MG, U-373 MG, and A-172) expressed endogenous mutant p53, and the other three (U-87 MG, EFC-2, and D54 MG) expressed wild-type p53. The restoration of normal p53-encoded protein in the mutant cell lines induced apoptosis as assessed by morphological studies using nuclear staining, electron microscopy, and flow cytometric assays. In wild-type p53 cell lines, however, the overexpression of wild-type p53 did not result in apoptosis but inhibited cellular proliferation rather drastically and modified the neoplastic phenotype. Differential effects suggest two pathways for glioma oncogenesis and a possible therapeutic strategy.. ...

Dendritic cells (DCs) are professional antigen presenting cells that are being considered as potential immunotherapeutic agents to promote host immune responses against tumor antigens. The use of such modified antigen-presenting cells for research or therapeutic have been limited by several factors, including maintaining DCs in a highly activated state, efficient transduction and expression, stable expression, identification of appropriate tumor-associated antigens, and absence of unintended functional changes or cytotoxicity. In this study, the feasibility of using CD34-DCs for tumor immunotherapy after transduction with a recombinant adenovirus containing HBsAg gene (AdVHBsAg), an HCC-associated antigen, was investigated. The gene transfer with recombinant adenovirus vectors (AdV) can obtained high levels of stable expression of HBsAg and its efficiency was increased in a multiplicity of infection (MOI)-dependent manner. Moreover, the AdVHBsAg infection had no appreciable effect on apoptosis ...

Chronic obstructive pulmonary disease (COPD) and lung cancer are major causes of death in the world. Exposure to tobacco smoke presents the main factor in the development of COPD. Epidemiological research has shown that COPD represents, regardless of smoking status, the biggest risk factor for developing lung cancer. The genetic basis of the association of these pathological entities is unknown. The regulation of the immune response plays an important role in maintaining homeostasis. Toll-like receptors (TLR) are important for initiating immunity by recognising the sequences associated with the pathogen and inducing signal pathways in the host as an antimicrobial response. Previous researches have shown that the genetic variant of TLR5, N592S gene, is associated with COPD and lung cancer. The aim of this research was to construct a replication-defective adenoviral vector by introducing a gene for TLR5wt and TLR5N592S into the adenovirus type 5 (Ad5) backbone that would allow the insertion of ...

Biological Sciences Shirley, Cat.No. AD00876Z Description Adenovirus with ORF of aminolevulinate dehydratase (ALAD) with C terminal Flag and His tag....

Dendritic cells (DCs) modified by some immunomodulatory genes can stimulate a strong antitumor immunity and improve the treatment of tumor cells on the condition that the sources of tumor-associated antigens (TAAs) are available. IL-6, a pleotropic cytokine, has been found to inhibit CD4+25+ regulatory T (Treg)-cell-mediated immune suppression and decrease activation-induced cell death (AICD) without interfering the process of T-cell activation. To enhance DC-based cancer vaccine, we engineered DCs to express transgene IL-6.. We constructed a fiber-modified recombinant adenovirus vector AdVIL-6 expressing IL-6, infected DCs with AdVIL-6, and then investigated the efficacy of antitumor immunity induced by vaccination with DCs engineered to express IL-6 transgene. We demonstrated that DCs infected with the recombinant adenovirus AdVIL-6 induced DC maturation by up-regulation of the expression of MHC class U (Iab), CD40, CD54 and CD80 expression. We also demonstrated that vaccination of OVA-pulsed ...

Described are vaccines comprising recombinant vectors, such as recombinant adenoviruses. The vectors comprise heterologous nucleic acids encoding at least two antigens from one or more tuberculosis-c

13:2; potential epub Adenovirus notions; tenure bhakti 1? On the epub Adenovirus Methods and of this interest, are above under form. 1282 An epub Adenovirus Methods and Protocols: Adenoviruses, Ad study read by Porten - Szubin 1987:187.

A quantum dot method for highly efficient labelling of single adenoviral particles is developed. The technique has no impact on viral fitness and allows the imaging and tracking of virus binding and internalisation events using a variety of techniques including imaging cytometry and confocal microscopy. The method is applied to characterise the tropism of different adenoviral vectors.. ...

Gene Therapy adenoviral vectors explained, information about the mechanism of Adenoviruses, Adeviral particle organisation and genome organisation of adenoviruses

As combining therapeutic agents with different action mechanisms may enhance efficacy, YSC-02, an oncolytic adenovirus with multi targets was loaded with five different genes, which were designed with the expectation that different action mechanisms would cooperate. In spite of concerns regarding many APIs, YSC-02 was constructed to be an adenovirus-based anti-cancer drug. By using our own established mouse model system suitable for efficient adenoviral infection and replication, immune activity as well as survival potential could be precisely estimated for anti-cancer drug efficacy. YSC-02 was designed to decrease tumor cell survival, metastasis and to increase tumor cell death, and immune activation. It is composed of five different target genes, including one fused form and two shRNAs, but each of these genes functions is closely linked to produce the maximal antitumor effect. YSC-02 is like an organic complex designed to be applied primarily to heterogeneous liver cancer and melanoma. The ...

This study was initiated with the original aim of assessing the consequences of the expression of the functional α2-subunit of the rat Na+-K+-ATPase in the neonatal rat cardiac myocytes lacking this isoform. It soon became evident, however, that only a truncated α2-subunit not likely to be functional was overexpressed in these cells. Because enzyme and receptor fragments may often act like inactive mutant variants and cause dominant negative inhibition (2, 10, 12, 23, 27, 36) we attempted to determine whether the expression of the α2-fragment impaired the function of endogenous Na+-K+-ATPase in the neonatal myocytes. Our findings clearly show that the ion transport function of Na+-K+-ATPase is indeed inhibited concomitant with the expression of the truncated α2-isoform and that this is accompanied by a significant reduction of the α1-protein content of the neonatal myocyte. Because the induced reduction of the α3-protein content is small, if any, and because it is established that α1 ...

The first region 4 open reading frame 3 protein FLNA (E4-ORF3; UniProt Identification type:entrez-protein attrs :text:P04489″ term_id :119084″ term_text :P04489″P04489) may be the most extremely conserved of most adenovirus-encoded gene items on the amino acidity level. supplementary/tertiary framework and the capability to type heterogeneous higher-order multimers in option. Importantly a non-functional E4-ORF3 mutant proteins L103A forms a well balanced dimer with WT supplementary structure content. As the L103A mutant is certainly Coumarin 30 not capable of PML reorganization this result shows that higher-order multimerization of E4-ORF3 could be necessary for the experience of the proteins. To get this hypothesis we demonstrate the fact that E4-ORF3 L103A mutant proteins works as a dominant-negative effector when coexpressed using the WT E4-ORF3 in mammalian cells. It prevents WT E4-ORF3-mediated PML monitor development presumably by binding towards the WT proteins and ...

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Much concern has focused on the direct toxic effects of adenoviruses, particularly as intravenous administration of the virus can induce acute liver injury, as shown in animal models. It is this effect which may have triggered the cascade of events leading to the death of the patient with OTC deficiency-in this case the recombinant virus was injected directly into the hepatic artery. Studies in mice have highlighted the dose limiting liver toxicity of intravenously administered virus, which in this model is mainly due to an acute inflammatory response involving the release of certain cytokines (interleukin 6, interleukin 8, tumour necrosis factor α) and the recruitment of immune effector cells into the liver.5-7These effects are manifest within the first few hours of adenovirus administration and do not require de novo virus gene expression. A recent study demonstrated that adenovirus induced chemokine gene expression within the liver occurs within one hour after infection and results in the ...

Description: Accurate measurement of adenovirus titer is critical for gene delivery. Traditional plaque-forming unit (PFU) assays are long and suffer from high inter-assay variability. The QuickTiter Adenovirus Titer Immunoassay Kit provide a quick, complete system to functionally titer virus infectivity. The assay recognizes all 41 serotypes of adenovirus, and can be used with any adenovirus system that can amplify in HEK 293 cells ...

Adenoviruses are ubiquitous. Weve all been infected with lots of them (gets to be a problem when making gene therapy vectors). The older you are, the more likely you have been exposed to the different kinds of adenovirus, to the point where if you are an adult reading this, you probably have antibodies to serotypes 1, 2, 5, and/or 6 (depending on where you live).. Thus older children are more likely to have been exposed to any adenovirus, including Ad-36. If your obese group of children is 63% kids aged 15-18, and your healthy weight group is only 17% 15-18, I am not shocked at all that antibodies to Ad-36 is correlated with obesity. I bet you could have picked any other adenovirus serotype and found the same correlation. But they didnt look.. William M. Briggs gets it. I dunno the dude. Statistician. But he gets it. *thumbs-up*. From a virologists perspective, there are putative, plausible mechanisms for how Ad-36 could actually play a role in obesity. Those reasonings require ongoing ...

When walking through the hospital you sense the enormity of the task at hand for the medical teams. Families are forced to sleep in corridors, on stairwells and in the grounds of the hospital. There simply are not enough members of staff to deal with the number of children in need of care and support. Although things are difficult, Adil says his mother is helping him to cope.. World Child Cancers appeal to Give the Gift of Growing Up aims to give children with cancer, just like Adil, hope for the future. His mother, Shusmita, says she used to want her son to study hard and earn a scholarship for university, but she now just hopes she can see her son survive his cancer and go back to his normal life. However, Adil has bigger plans;. ...