Preexisting immunity to adenovirus in rhesus monkeys fails to prevent vector-induced toxicityAndrei N Varnavski
Institute for Human Gene Therapy and Department of Molecular and Cellular Engineering, University of Pennsylvania and The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
J Virol 76:5711-9. 2002
..Furthermore, preexisting immunity appears to induce a vector-specific inhibitory effect on erythroid progenitor development in the bone marrow that is not found when naive animals are challenged with vector...
- Role of CCR5 and its ligands in the control of vascular inflammation and leukocyte recruitment required for acute excitotoxic seizure induction and neural damage
Jean Pierre Louboutin
Department of Pathology, Jefferson Medical College, 1020 Locust St, Rm 251, Philadelphia, PA 19107, USA
FASEB J 25:737-53. 2011
..Controls received unrelated SV(BUGT) vectors. Decrease in CCR5 in circulating cells strongly protected from excitotoxin-induced seizures, BBB leakage, CNS injury, and inflammation, and facilitated neurogenic repair...
HIV-1 gp120-induced injury to the blood-brain barrier: role of metalloproteinases 2 and 9 and relationship to oxidative stressJean Pierre Louboutin
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
J Neuropathol Exp Neurol 69:801-16. 2010
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- Dopaminergic neurotoxicity of HIV-1 gp120: reactive oxygen species as signaling intermediates
Lokesh Agrawal
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
Brain Res 1306:116-30. 2010
..These findings may help explain why DN loss and Parkinson's-like dysfunction predominate in neuroAIDS and may apply to other neurodegenerative diseases involving the SN...
- HIV-1 gp120 neurotoxicity proximally and at a distance from the point of exposure: protection by rSV40 delivery of antioxidant enzymes
Jean Pierre Louboutin
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Neurobiol Dis 34:462-76. 2009
..Thus, SN dopaminergic neurons are highly sensitive to HIV-1 gp120-induced neurotoxicity, and antioxidant gene delivery, even at a distance, is protective...
- Ethanol protects from injury due to ischemia and reperfusion by increasing vascularity via vascular endothelial growth factor
Jean Pierre Louboutin
Department of Pathology and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Alcohol 46:441-54. 2012
..Moreover, the ethanol-induced increase of blood vessel density is protective against ischemic events (i.e., hindlimb ischemia and myocardium ischemia/reperfusion) and promotes skeletal muscle regeneration...
- Gene delivery of antioxidant enzymes inhibits human immunodeficiency virus type 1 gp120-induced expression of caspases
J P Louboutin
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, United States
Neuroscience 214:68-77. 2012
..Thus, HIV-1 gp120 increased caspases expression in the CP. Prior antioxidant enzyme treatment mitigated production of these caspases, probably by reducing ROS levels...
- Blood-brain barrier abnormalities caused by HIV-1 gp120: mechanistic and therapeutic implications
Jean Pierre Louboutin
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street Room 255 Philadelphia, PA 19107, USA
ScientificWorldJournal 2012:482575. 2012
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- Intracisternal rSV40 administration provides effective pan-CNS transgene expression
J P Louboutin
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
Gene Ther 19:114-8. 2012
..Thus, intracisternal administration of antioxidant-carrying rSV40 vectors may be useful in treating widespread CNS diseases such as HIV-1-associated neurocognitive disorders characterized by oxidative stress...
In vivo gene transfer to the CNS using recombinant SV40-derived vectorsJean Pierre Louboutin
Thomas Jefferson University, Department of Pathology, Anatomy and Cell Biology, 1020 Locust Street, Room 255, Philadelphia, PA 19107, USA
Expert Opin Biol Ther 8:1319-35. 2008
..Gene transfer to the CNS has been approached using various vectors...
- Protecting neurons from HIV-1 gp120-induced oxidant stress using both localized intracerebral and generalized intraventricular administration of antioxidant enzymes delivered by SV40-derived vectors
J P Louboutin
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Gene Ther 14:1650-61. 2007
..These findings suggest the potential utility of both localized and widespread gene delivery in treating neuroAIDS and other CNS diseases characterized by excessive oxidative stress...
- A rat model of human immunodeficiency virus 1 encephalopathy using envelope glycoprotein gp120 expression delivered by SV40 vectors
Jean Pierre Louboutin
Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, USA
J Neuropathol Exp Neurol 68:456-73. 2009
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- HIV-1 gp120-induced neuroinflammation: relationship to neuron loss and protection by rSV40-delivered antioxidant enzymes
Jean Pierre Louboutin
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Room 255, Philadelphia, PA 19107, USA
Exp Neurol 221:231-45. 2010
..Thus, gp120-induced CNS injury, neuron loss and inflammation may be mitigated by antioxidant gene delivery...
- Blood-brain barrier abnormalities caused by exposure to HIV-1 gp120--protection by gene delivery of antioxidant enzymes
Jean Pierre Louboutin
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Neurobiol Dis 38:313-25. 2010
..Thus: acute and chronic exposure to gp120 disrupts the BBB; gp120-mediated BBB abnormalities are related to lesions of brain microvessels; and gp120 is directly toxic to brain endothelial cells...
- Gene transfer to the cerebellum
Jean Pierre Louboutin
Department of Pathology, Jefferson Medical College, Thomas Jefferson University, 1020 Locust Street, Room 255, Philadelphia, PA 19107, USA
Cerebellum 9:587-97. 2010
..No inflammatory or other reaction was detected at any time. Thus, SV40-derived vectors can deliver effective, safe, and durable transgene expression to the cerebellum...
- Efficient CNS gene delivery by intravenous injection
Jean Pierre Louboutin
Department of Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
Nat Methods 7:905-7. 2010
..Intravenous injection of rSV40s, particularly with mannitol pretreatment, resulted in extensive expression of multiple transgenes throughout the CNS...
- Bone marrow-derived cells migrate to line the vessels of the CNS: opportunities for gene delivery to CNS vasculature
J P Louboutin
Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Neuroscience 195:215-23. 2011
..Intramarrow gene delivery may provide an avenue to deliver genes to the vascular endothelium of the CNS...
- HIV-1 gp120 upregulates matrix metalloproteinases and their inhibitors in a rat model of HIV encephalopathy
Jean Pierre Louboutin
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Eur J Neurosci 34:2015-23. 2011
..Thus, HIV-1 gp120 upregulated TIMP-1 and TIMP-2 in the CP. Prior antioxidant enzyme treatment mitigated production of these TIMPs, probably by reducing MMP expression...
- Delivering genes to the organ-localized immune system: long-term results of direct intramarrow transduction
Jean Pierre Louboutin
Department of Pathology, Jefferson Medical College, Philadelphia, PA 19107, USA
J Gene Med 9:843-51. 2007
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- Strategies for CNS-directed gene delivery: in vivo gene transfer to the brain using SV40-derived vectors
J P Louboutin
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Gene Ther 14:939-49. 2007
..SV40-derived vectors may, thus, be useful for long-term gene expression in the brain, whether locally by intraparenchymal administration or diffusely by intraventricular injection, with or without mannitol...
- S-protein is expressed in necrotic fibers in Duchenne muscular dystrophy and polymyositis
Jean Pierre Louboutin
Department of Medicine, Division of Medical Genetics, University of Pennsylvania School of Medicine, Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104 4268, USA
Muscle Nerve 27:575-81. 2003
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- Rat bone marrow progenitor cells transduced in situ by rSV40 vectors differentiate into multiple central nervous system cell lineages
Jean Pierre Louboutin
Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, 1020 Locust Street, Philadelphia, Pennsylvania 19107, USA
Stem Cells 24:2801-9. 2006
..6%), as determined by double immunostaining for FLAG and lineage markers. These data suggest that one or more populations of cells resident within adult bone marrow can migrate to the brain and differentiate into CNS-specific cells...
- HIV-1 Tat neurotoxicity: a model of acute and chronic exposure, and neuroprotection by gene delivery of antioxidant enzymes
Lokesh Agrawal
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Neurobiol Dis 45:657-70. 2012
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- Preventing HIV-1 Tat-induced neuronal apoptosis using antioxidant enzymes: mechanistic and therapeutic implications
Lokesh Agrawal
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Room 251, 1020 Locust Street, Philadelphia, PA 19107, USA
Virology 363:462-72. 2007
..Tat therefore activates multiple signaling pathways, in one of which superoxide acts as an intermediate while the other utilizes peroxide. Gene delivery to protect neurons from Tat must therefore target both...
- Toll-like receptor 4 mediates innate immune responses to Haemophilus influenzae infection in mouse lung
Xiaorong Wang
Institute for Human Gene Therapy, Department of Molecular and Cellular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
J Immunol 168:810-5. 2002
..influenzae in the lung. This suggests that the airway epithelia might contribute to sensing of H. influenzae infection and signaling the innate immune response...
- Long-term gene expression in dividing and nondividing cells using SV40-derived vectors
David S Strayer
Department of Pathology and Cell Biology, Jefferson Medical College, Philadelphia, PA, USA
Mol Biotechnol 34:257-70. 2006
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- Human airway epithelial cells sense Pseudomonas aeruginosa infection via recognition of flagellin by Toll-like receptor 5
Zhe Zhang
Gene Therapy Program, Division of Medical Genetics, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
Infect Immun 73:7151-60. 2005
..These findings demonstrate that the airway epithelial receptor TLR5 senses P. aeruginosa through its flagellin protein, which may have an important role in the initiation of the host inflammatory reaction to clear the invading pathogen...
- Lymphocyte adhesion to CCR5 ligands is reduced by anti-CCR5 gene delivery
Elena Marusich
Department of Pathology, Jefferson Medical College, Thomas Jefferson University, 1020 Locust Street, Philadelphia, Pennsylvania 19107, USA
J Neurol Sci 308:25-7. 2011
..These data suggest that reducing CCR5 in peripheral blood mononuclear cells (PBMCs) might alter their adhesion to the microvasculature and their participation in inflammatory processes...
- Airway epithelia regulate expression of human beta-defensin 2 through Toll-like receptor 2
Xiaorong Wang
Department of Medicine, Medical Genetics Division, University of Pennsylvania School of Medicine, Philadelphia, USA
FASEB J 17:1727-9. 2003
..These data provide convincing evidence that up-regulation of hBD2 can be induced through hTLR2-mediated NFkappaB/IkappaB pathway in the human airway epithelial cells...
- Correction of the dystrophic phenotype by in vivo targeting of muscle progenitor cells
Gary P Kobinger
Gene Therapy Program, Division of Medical Genetics, University of Pennsylvania Health System, Philadelphia, Pennsylvania 19104, USA
Hum Gene Ther 14:1441-9. 2003
..This study shows that progenitor cells can be genetically engineered in vivo and subsequently proliferate into terminally differentiated tissue carrying the genetic graft in a way that stably corrects function...
- Transduction of satellite cells after prenatal intramuscular administration of lentiviral vectors
Tippi C MacKenzie
The Children's Institute for Surgical Science, Children's Hospital of Philadelphia, Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104-4318, USA
J Gene Med 7:50-8. 2005
..These findings may have important implications for gene therapy strategies directed toward muscular dystrophy...
- APCs in the liver and spleen recruit activated allogeneic CD8+ T cells to elicit hepatic graft-versus-host disease
Yi Zhang
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
J Immunol 169:7111-8. 2002
..Thus, tissue-resident APCs control the local recruitment of allo-reactive donor T cells and the subsequent development of acute GVHD...
- In vivo quantitative noninvasive imaging of gene transfer by single-photon emission computerized tomography
Alberto Auricchio
Department of Medicine, and The Wistar Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Hum Gene Ther 14:255-61. 2003
..This should be useful to monitor gene transfer in the settings of gene therapy...
- Gene transfer into skeletal muscle using novel AAV serotypes
Jean-Pierre Louboutin
Gene Therapy Program, Department of Medicine, Division of Medical Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA
J Gene Med 7:442-51. 2005
..DISCUSSION: These results show that AAV2/7 and AAV2/8 are able to transduce muscle fibers of immunocompetent mice very efficiently, offering new perspectives in gene transfer of skeletal muscle...
- Transduction of human islets with pseudotyped lentiviral vectors
Gary P Kobinger
Gene Therapy Program, Division of Medical Genetics, Department of Medicine, University of Pennsylvania Health System, Philadelphia, PA 19104, USA
Hum Gene Ther 15:211-9. 2004
..Overall, our study describes an improved methodology for achieving safe and efficient gene transfer into cells of human islets...
- Gene therapy with novel adeno-associated virus vectors substantially diminishes atherosclerosis in a murine model of familial hypercholesterolemia
Corinna Lebherz
Gene Therapy Program, Division of Medical Genetics, The University of Pennsylvania School of Medicine, Pennsylvania, USA
J Gene Med 6:663-72. 2004
..CONCLUSIONS: Using vectors based on novel nonhuman primate AAVs, which provide advantages in terms of efficiency, we were able to achieve a long-term correction of the metabolic defect in LDL receptor deficient mice...
- The p38 mitogen-activated protein kinase signaling pathway is coupled to Toll-like receptor 5 to mediate gene regulation in response to Pseudomonas aeruginosa infection in human airway epithelial cells
Zhe Zhang
Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Infect Immun 75:5985-92. 2007
..These results demonstrate a role for p38 MAPK signaling in gene regulation in response to P. aeruginosa via TLR5...
- Novel adenoviral vectors coding for GFP-tagged wtCFTR and deltaF508-CFTR: characterization of expression and electrophysiological properties in A549 cells
Horia Vais
Division of Medical Genetics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Pflugers Arch 449:278-87. 2004
..The data show that high levels of functional GFP-tagged CFTR channels can be expressed with these adenoviral vector constructs...
