المؤلفون: Karil Abrahamsen, D Brough, H L Kong, A Lizonova, Andrea Mastrangeli, Erik Falck-Pedersen, Ronald G. Crystal

المصدر: Journal of Virology. 71:8946-8951

مصطلحات موضوعية: Gene Expression Regulation, Viral, viruses, Transgene, Genetic Vectors, Immunology, Biology, Virus Replication, Microbiology, Virus, Defective virus, Chloramphenicol acetyltransferase, Mice, Plasmid, Transduction, Genetic, Virology, Animals, Humans, Vector (molecular biology), Cells, Cultured, Adenovirus genome, Adenoviruses, Human, Gene Transfer Techniques, Defective Viruses, Molecular biology, Viral replication, Insect Science, Adenovirus E1A Proteins, Research Article

الوصف: A strategy for constructing replication-defective adenovirus vectors from non-subgroup C viruses has been successfully demonstrated with adenovirus type 7 strain a (Ad7a) as the prototype. An E1A-deleted Ad7a reporter virus expressing the chloramphenicol acetyltransferase (CAT) gene from the cytomegalovirus promoter enhancer was constructed with DNA fragments isolated from Ad7a, an Ad7a recombination reporter plasmid, and the 293 cell line. The Ad7a-CAT virus particle transduces A549 cells as efficiently as Ad5-based vectors. Intravenous infections in a murine model indicate that the Ad7a-CAT virus infects a variety of tissues, with maximal levels of CAT gene expression found in the liver. The duration of Ad7a-CAT transgene expression in the liver was maximally maintained 2 weeks postinfection, with a decline to baseline activity by the week 4 postinfection. Ad7a-CAT represents the first example of a non-subgroup C E1A- adenovirus gene transfer vector.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c7be7bad30c94b03c10fe8431b60e38Test
https://doi.org/10.1128/jvi.71.11.8946-8951.1997Test

المؤلفون: Wenru Song, Ronald G. Crystal, Ben-Gary Harvey, Christopher J. Magovern, Heather Carpenter, Tom Wickham, Neil R. Hackett, Charles A. Mack, Todd K. Rosengart, Eric Falck-Pedersen, Andrea Mastrangeli, O. Wayne Isom, Imre Kovesdi

المصدر: Human Gene Therapy. 8:99-109

مصطلحات موضوعية: Chloramphenicol O-Acetyltransferase, Gene Expression Regulation, Viral, Transgene, Genetic Vectors, Mice, Inbred Strains, Antibodies, Adenoviridae, Viral vector, Rats, Sprague-Dawley, Mice, Viral Proteins, Immune system, Immunity, Genetics, Animals, Vector (molecular biology), Serotyping, Lung, Molecular Biology, Cells, Cultured, Glucuronidase, biology, Gene Transfer Techniques, Virology, Rats, Humoral immunity, Immunology, biology.protein, Systemic administration, Molecular Medicine, Antibody, Bronchoalveolar Lavage Fluid, T-Lymphocytes, Cytotoxic

الوصف: Effective gene transfer and expression following repetitive administration of adenoviral (Ad) vectors in experimental animals is limited by anti-Ad neutralizing antibodies. Knowing that anti-Ad humoral immunity is serotype-specific, we hypothesized that anti-Ad neutralizing immunity could be circumvented using Ad vectors of different serotypes (Ad2, Ad5) within the same subgroup (C) to transfer and express beta-glucuronidase (beta glu) in the lung. Sprague-Dawley rats received an intratracheal administration of either Ad2 beta glu or Ad5 beta glu, and, 14 days later, repeat administration of either the same vector or a vector of a different serotype. Analysis of serum and bronchoalveolar lavage fluid following initial vector administration demonstrated systemic and local serotype-specific neutralizing antibodies. For both the Ad2 and Ad5 vectors, beta glu expression 24 hr following the second administration of the same serotype was30% of that of naive animals. In contrast, beta glu expression 24 hr following second administration of a different serotype Ad vector was similar to expression at 24 hr of naive animals receiving a single administration (Ad5 beta glu followed by Ad2 beta glu, as well as Ad2 beta glu followed by Ad5 beta glu; p0.2 both comparisons). Although the alternative serotype bypassed anti-Ad neutralizing immunity, persistence of expression was reduced compared to that following administration to naive animals. Compatible with this observation, systemic administration of the same vectors to C57B1/6 mice demonstrated induction of cytotoxic T lymphocytes directed against the beta glu transgene, as well as products of the Ad genome. Interestingly, intratracheal administration of vectors with different serotypes and different transgenes to rats resulted in longer expression (but still not normalized) compared to that achieved with vectors of different serotypes but the same transgene. These observations demonstrate that alternate use of Ad vectors from different serotypes within the same subgroup can circumvent anti-Ad humoral immunity to permit effective gene transfer after repeat administration, although the chronicity of expression is limited, likely by cellular immune process directed against both the transgene and viral gene products expressed by the vector.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::307fefe9aa810ae48c37fa0b42f40137Test
https://doi.org/10.1089/hum.1997.8.1-99Test

المؤلفون: Gerhard Wolff, Jeffrey Yao, Ronald G. Crystal, Erik Falck-Pedersen, Andrea Mastrangeli, Ben-Gary Harvey, Imre Kovesdi

المصدر: Human Gene Therapy. 7:79-87

مصطلحات موضوعية: Chloramphenicol O-Acetyltransferase, Male, congenital, hereditary, and neonatal diseases and abnormalities, Genetic Vectors, Cystic Fibrosis Transmembrane Conductance Regulator, Gene Expression, Gene transfer, Biology, law.invention, Viral vector, Rats, Sprague-Dawley, Immune system, Neutralization Tests, law, In vivo, Genetics, Animals, Humans, RNA, Messenger, Serotyping, Lung, Molecular Biology, Adenoviruses, Human, Gene Transfer Techniques, Virology, Cystic fibrosis transmembrane conductance regulator, Rats, Recombinant DNA, biology.protein, Molecular Medicine, Female, Adenovirus serotype

الوصف: Recombinant, replication-deficient adenovirus (Ad) vectors have been successfully used to transfer and express the normal human cystic fibrosis transmembrane conductance regulator (CFTR) cDNA in vivo in the respiratory epithelium of experimental animals and humans with cystic fibrosis (CF). Since Ad-directed gene expression wanes over time, repeat administration is necessary to achieve an effective treatment for CF. A major hurdle to such a strategy is the possibility that anti-Ad humoral immunity may prevent gene expression in individuals with pre-existing anti-Ad immunity or following repeat administration. One strategy to circumvent such a problem would be alternating the use of Ad vectors belonging to different subgroups. Neutralizing antibodies developed with the administration of one Ad serotype do not cross-react with an Ad belonging to a second serotype in a manner that blocks infection and gene expression. To test this hypothesis, an immunizing dose of wild-type Ad5 (subgroup C), Ad4 (subgroup E), or Ad30 (subgroup D) was administered intratracheally to experimental animals, followed by an intratracheal administration of a replication-deficient subgroup C-derived vector coding for marker genes (chloramphenicol acetyl transferase or beta-galactosidase) or for the normal human CFTR cDNA. As expected, studies with vectors coding for marker genes or for CFTR cDNA demonstrated that airway administration of a vector does not yield efficient gene transfer, if there has been prior recent airway administration of the same Ad subgroup. In contrast, effective expression from the second administration can be achieved with an adenovirus vector belonging to a subgroup different from the first adenovirus administered. These data support the paradigm of alternating Ad vectors derived from different subgroups as strategy to circumvent anti-Ad humoral immunity, thus permitting the use of Ad vectors as a means to treat the respiratory manifestations of CF.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e6ca2ec7368a5f0cede5b7c8c8f975cTest
https://doi.org/10.1089/hum.1996.7.1-79Test

المؤلفون: Andrea Mastrangeli, Ronald G. Crystal, Donald K. Ingram, Hui Kuo

المصدر: Brain Research. 705:31-38

مصطلحات موضوعية: Male, Microinjections, Recombinant Fusion Proteins, Genetic Vectors, Central nervous system, DNA, Recombinant, Substantia nigra, Striatum, Biology, Axonal Transport, Corpus Callosum, Viral vector, Rats, Sprague-Dawley, Basal ganglia, medicine, Animals, Vector (molecular biology), Molecular Biology, Afferent Pathways, Adenoviruses, Human, General Neuroscience, Gene Transfer Techniques, Brain, Defective Viruses, beta-Galactosidase, Rats, Cell biology, Neostriatum, medicine.anatomical_structure, Lac Operon, Cerebral cortex, DNA, Viral, Axoplasmic transport, Replicon, Neurology (clinical), Neuroscience, Developmental Biology

الوصف: 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 that adenoviral vectors can be useful retrograde tracers in the study of afferent connections within the central nervous system.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c6a7a0148d56c774ca17bc0dcb1729eTest
https://doi.org/10.1016/0006-8993Test(95)01065-3

المؤلفون: Vinay Sikand, Joseph Cooke, Juan Herena, Diego Diaz, Francisco Pacheco, Abraham Sanders, Fred Gilbert, Thomas J. Russi, Claudia I. Henschke, Co-Investigators: Andrea Mastrangeli, Principal Investigator: Ronald G. Crystal, William R. Pascal, Peter Brion, Thomas King, Edward A. Hirschowitz, Ben-Gary Harvey

المصدر: Human Gene Therapy. 6:667-703

مصطلحات موضوعية: Pathology, medicine.medical_specialty, biology, business.industry, medicine.disease, Cystic fibrosis, Cystic fibrosis transmembrane conductance regulator, law.invention, Viral replication, law, Complementary DNA, Genetics, Recombinant DNA, biology.protein, Molecular Medicine, Medicine, business, Molecular Biology

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::01e5c383ccd43dd0838fffe09b01c4f5Test
https://doi.org/10.1089/hum.1995.6.5-667Test

المؤلفون: Sanford H. Feldman, Gianluigi Bajocchi, Ronald G. Crystal, Andrea Mastrangeli

المصدر: Nature Genetics. 3:229-234

مصطلحات موضوعية: Ependymal Cell, viruses, Genetic enhancement, Central nervous system, Substantia nigra, Transfection, Biology, Molecular biology, medicine.anatomical_structure, Globus pallidus, nervous system, Stereotaxic technique, Genetics, medicine, Ependyma

الوصف: To evaluate the potential for adenovirus-mediated central nervous system (CNS) gene transfer, the replication deficient recombinant adenovirus vectors Ad.RSV beta gal (coding for beta-galactosidase) and Ad-alpha 1AT (coding for human alpha 1-antitrypsin) were administered to the lateral ventricle of rats. Ad.RSV beta gal transferred beta-galactosidase to ependymal cells lining the ventricles whereas Ad-alpha 1AT mediated alpha 1-antitrypsin secretion into the cerebral spinal fluid for 1 week. These observations, together with beta-galactosidase activity in the globus pallidus and substantia nigra following stereotactic administration of Ad.RSV beta gal to the globus pallidus, suggest that adenovirus vectors will be useful for CNS gene therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::c8489ef8f225b05cf8679c24d4aef744Test
https://doi.org/10.1038/ng0393-229Test

المؤلفون: Michel Perricaudet, Ronald G. Crystal, J P Lecocq, Melissa A. Rosenfeld, Andrea Pavirani, Andrea Mastrangeli, Claire Danel, L D Stratford-Perricaudet

المصدر: Journal of Clinical Investigation. 91:225-234

مصطلحات موضوعية: Gene Expression Regulation, Viral, Male, Cell type, Genetic enhancement, Genetic Vectors, Bronchi, Biology, Transfection, Cystic fibrosis, Epithelium, Gene Expression Regulation, Enzymologic, In vivo, Escherichia coli, medicine, Animals, Sigmodontinae, Lung, Recombination, Genetic, Regulation of gene expression, Cell growth, Adenoviruses, Human, Epithelial Cells, Genetic Therapy, General Medicine, respiratory system, beta-Galactosidase, medicine.disease, Cell biology, DNA, Viral, Immunology, Respiratory epithelium, Female, Gene Deletion, Research Article

الوصف: A variety of pulmonary disorders, including cystic fibrosis, are potentially amenable to treatment in which a therapeutic gene is directly transferred to the bronchial epithelium. This is difficult to accomplish because the majority of airway epithelial cells replicate slowly and/or are terminally differentiated. Adenovirus vectors may circumvent this problem, since they do not require target cell proliferation to express exogenous genes. To evaluate the diversity of airway epithelial cell targets for in vivo adenovirus-directed gene transfer, a replication deficient recombinant adenovirus containing the Escherichia coli lacZ (beta-galactosidase [beta-gal]) gene (Ad.RSV beta gal) was used to infect lungs of cotton rats. In contrast to uninfected animals, intratracheal Ad.RSV beta gal administration resulted in beta-gal activity in lung lysate and cytochemical staining in all cell types forming the airway epithelium. The expression of the exogenous gene was dose-dependent, and the distribution of the beta-gal positive airway epithelial cells in Ad.RSV beta gal-infected animals was similar to the normal cell differential of the control animals. Thus, a replication deficient recombinant adenovirus can transfer an exogenous gene to all major categories of airway epithelial cells in vivo, suggesting that adenovirus vectors may be an efficient strategy for in vivo gene transfer in airway disorders such as cystic fibrosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::14cd4a904c6d548e61ff5c3334bae694Test
https://doi.org/10.1172/jci116175Test

المؤلفون: Andrea Mastrangeli, Joseph Cooke, Roy Silverstein, Michael D. Lieberman, Thomas J. Russi, David F. Yankelevitz, Akihiko Ohwada, Ronald G. Crystal, Edward A. Hirschowitz, John M. Daly, Nancy E. Kemeny, Ben-Gary Harvey, Elias Kazam, Abraham Sanders, Claudia I. Henschke

المصدر: Human gene therapy. 8(8)

مصطلحات موضوعية: Adult, Male, Adolescent, Antimetabolites, Genetic Vectors, Administration, Oral, Flucytosine, Nucleoside Deaminases, Virus Replication, Genetic therapy, Viral vector, Adenoviridae, Cytosine Deaminase, Colon carcinoma, Oral administration, Genetics, Escherichia coli, Medicine, Humans, Prodrugs, Molecular Biology, Gene, business.industry, Cytosine deaminase, Liver Neoplasms, Genetic Therapy, Prodrug, Virology, Phase i study, Colonic Neoplasms, Molecular Medicine, Female, business

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a16d35ecc147f96d746d5601dbcb624bTest
https://pubmed.ncbi.nlm.nih.gov/9195221Test

المؤلفون: Thomas J. Walsh, Tao Xu, Frank G. Oppenheim, Ronald G. Crystal, Andrea Mastrangeli, Brian O'Connell, Tin Sein, Bruce J. Baum

المصدر: Human gene therapy. 7(18)

مصطلحات موضوعية: Male, Saliva, Antifungal Agents, Genetic Vectors, Submandibular Gland, DNA, Recombinant, Gene Expression, Histatins, Microbial Sensitivity Tests, medicine.disease_cause, Salivary Glands, Microbiology, Adenoviridae, Cell Line, stomatognathic system, Gene expression, Candida albicans, Genetics, medicine, Animals, Humans, RNA, Messenger, Rats, Wistar, Salivary Proteins and Peptides, Molecular Biology, Fluconazole, Histatin 3, biology, Gene Transfer Techniques, Proteins, Epithelial Cells, biology.organism_classification, Corpus albicans, Recombinant Proteins, Rats, Histatin, Immunology, Molecular Medicine, medicine.drug

الوصف: Mucosal candidiasis, the most common opportunistic fungal infection in human immunodeficiency virus (HIV)-infected patients, is an early sign of clinically overt acquired immunodeficiency syndrome (AIDS) and an important cause of morbidity, particularly in HIV-infected children. The appearance of azole-resistant strains of Candida albicans had made clinical management of candidiasis increasingly difficult. We propose a novel approach to the management of candidal infections that involves the use of naturally occurring antifungal proteins, such as the histatins. Histatins are a family of small proteins that are secreted in human saliva. We have constructed recombinant adenovirus vectors that contain the histatin 3 cDNA. These vectors are capable of directing the expression of histatin 3 in the saliva of rats at up to 1,045 micrograms/ml, well above the levels found in normal human saliva. The adenovirus-directed histatin demonstrated a 90% candidacidal effect in the timed-kill assay against both fluconazole-susceptible and fluconazole-resistant strains of C. albicans and inhibited germination by 45% in the same strains. These studies suggest that a gene transfer approach to overexpress naturally occurring antifungal proteins may be useful in the management of mucosal candidiasis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bf019fb103629c84f1abfb0beb3e7a1eTest
https://pubmed.ncbi.nlm.nih.gov/8953316Test

المؤلفون: Andrea Mastrangeli, Ronald G. Crystal, Marcos Heinflink, Marvin C. Gershengorn, Erik Falck-Pedersen, Gerhard Wolff

المصدر: Nature genetics. 12(3)

مصطلحات موضوعية: Blood Glucose, medicine.medical_specialty, Recombinant Fusion Proteins, Genetic Vectors, Thyrotropin-releasing hormone, Biology, Phosphatidylinositols, Glucagon, Adenoviridae, Rats, Sprague-Dawley, Mice, Thyrotropin-releasing hormone receptor, Internal medicine, Genetics, medicine, Animals, Receptor, Thyrotropin-Releasing Hormone, Cells, Cultured, Phosphoinositide Pathway, Receptors, Thyrotropin-Releasing Hormone, Gene Transfer Techniques, Rats, Endocrinology, Liver, Feasibility Studies, Ectopic expression, Liver function, Signal transduction, Signal Transduction

الوصف: Maintenance of blood glucose by the liver is normally initiated by extracellular regulatory molecules such as glucagon and vasopressin triggering specific hepatocyte receptors to activate the cAMP or phosphoinositide signal transduction pathways, respectively. We now show that the normal ligand-receptor regulators of blood glucose in the liver can be bypassed using an adenovirus vector expressing the mouse pituitary thyrotropin releasing hormone receptor (TRHR) cDNA ectopically in rat liver in vivo. The ectopically expressed TRHR links to the phosphoinositide pathway, providing a means to regulate liver function with TRH, an extracellular ligand that does not normally affect hepatic function. Administration of TRH to these animals activates the phosphoinositide pathway, resulting in a sustained rise in blood glucose. It should be possible to use this general strategy to modulate the differentiated functions of target organs in a wide variety of pathologic states.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91464ba063399674a97dd5443eb3314bTest
https://pubmed.ncbi.nlm.nih.gov/8589718Test