dependovirus

Summary

Summary: A genus of the family PARVOVIRIDAE, subfamily PARVOVIRINAE, which are dependent on a coinfection with helper adenoviruses or herpesviruses for their efficient replication. The type species is Adeno-associated virus 2.

Top Publications

  1. pmc Safety and efficacy of gene transfer for Leber's congenital amaurosis
    Albert M Maguire
    Scheie Eye Institute, University of Pennsylvania, USA
    N Engl J Med 358:2240-8. 2008
  2. pmc Adenovirus-associated virus vector-mediated gene transfer in hemophilia B
    Amit C Nathwani
    Department of Haematology, University College London Cancer Institute, London, United Kingdom
    N Engl J Med 365:2357-65. 2011
  3. pmc Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years
    Samuel G Jacobson
    Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA
    Arch Ophthalmol 130:9-24. 2012
  4. ncbi Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response
    Catherine S Manno
    The Children s Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania, 19104, USA
    Nat Med 12:342-7. 2006
  5. pmc Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy
    Guang Ping Gao
    Institute for Human Gene Therapy and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 99:11854-9. 2002
  6. ncbi Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection
    Carmela Zincarelli
    Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Mol Ther 16:1073-80. 2008
  7. pmc Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial
    William W Hauswirth
    Department of Ophthalmology, University of Florida, Gainesville, FL 32610, USA
    Hum Gene Ther 19:979-90. 2008
  8. ncbi Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges
    Federico Mingozzi
    Center for Cellular and Molecular Therapeutics, The Children s Hospital of Philadelphia, 3501 Civic Center Boulevard, 5th Floor CTRB, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Genet 12:341-55. 2011
  9. ncbi Effect of gene therapy on visual function in Leber's congenital amaurosis
    James W B Bainbridge
    Institute of Ophthalmology, University College London, London, United Kingdom
    N Engl J Med 358:2231-9. 2008
  10. pmc Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes
    Kevin D Foust
    Center for Gene Therapy, The Research Institute at Nationwide Children s Hospital, 700 Children s Drive, Columbus, Ohio 43205, USA
    Nat Biotechnol 27:59-65. 2009

Detail Information

Publications352 found, 100 shown here

  1. pmc Safety and efficacy of gene transfer for Leber's congenital amaurosis
    Albert M Maguire
    Scheie Eye Institute, University of Pennsylvania, USA
    N Engl J Med 358:2240-8. 2008
    ..Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA...
  2. pmc Adenovirus-associated virus vector-mediated gene transfer in hemophilia B
    Amit C Nathwani
    Department of Haematology, University College London Cancer Institute, London, United Kingdom
    N Engl J Med 365:2357-65. 2011
    ..Hemophilia B, an X-linked disorder, is ideally suited for gene therapy. We investigated the use of a new gene therapy in patients with the disorder...
  3. pmc Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years
    Samuel G Jacobson
    Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA
    Arch Ophthalmol 130:9-24. 2012
    ..To determine the safety and efficacy of subretinal gene therapy in the RPE65 form of Leber congenital amaurosis using recombinant adeno-associated virus 2 (rAAV2) carrying the RPE65 gene...
  4. ncbi Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response
    Catherine S Manno
    The Children s Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania, 19104, USA
    Nat Med 12:342-7. 2006
    ..We conclude that rAAV-2 vectors can transduce human hepatocytes in vivo to result in therapeutically relevant levels of F.IX, but that future studies in humans may require immunomodulation to achieve long-term expression...
  5. pmc Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy
    Guang Ping Gao
    Institute for Human Gene Therapy and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 99:11854-9. 2002
    ....
  6. ncbi Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection
    Carmela Zincarelli
    Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Mol Ther 16:1073-80. 2008
    ..AAV6 expression was observed in the heart, liver, and skeletal muscle, and the genome distribution corroborated these observations...
  7. pmc Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial
    William W Hauswirth
    Department of Ophthalmology, University of Florida, Gainesville, FL 32610, USA
    Hum Gene Ther 19:979-90. 2008
    ..99). Comparisons are drawn between the present work and two other studies of ocular gene therapy for RPE65-LCA that were carried out contemporaneously and reported...
  8. ncbi Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges
    Federico Mingozzi
    Center for Cellular and Molecular Therapeutics, The Children s Hospital of Philadelphia, 3501 Civic Center Boulevard, 5th Floor CTRB, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Genet 12:341-55. 2011
    ..Recent exciting results have raised hopes for the treatment of many other diseases. As we discuss here, the prospects and challenges for AAV gene therapy are to a large extent dependent on the target tissue and the specific disease...
  9. ncbi Effect of gene therapy on visual function in Leber's congenital amaurosis
    James W B Bainbridge
    Institute of Ophthalmology, University College London, London, United Kingdom
    N Engl J Med 358:2231-9. 2008
    ..These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747 [ClinicalTrials.gov].)...
  10. pmc Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes
    Kevin D Foust
    Center for Gene Therapy, The Research Institute at Nationwide Children s Hospital, 700 Children s Drive, Columbus, Ohio 43205, USA
    Nat Biotechnol 27:59-65. 2009
    ..It may also be useful for rapid postnatal genetic manipulations in basic neuroscience studies...
  11. pmc Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration
    Francesca Simonelli
    Department of Ophthalmology, Second University of Naples, Naples, Italy
    Mol Ther 18:643-50. 2010
    ..The safety of the intervention and the stability of the improvement in visual and retinal function in these subjects support the use of AAV-mediated gene augmentation therapy for treatment of inherited retinal diseases...
  12. ncbi Recombinant AAV viral vectors pseudotyped with viral capsids from serotypes 1, 2, and 5 display differential efficiency and cell tropism after delivery to different regions of the central nervous system
    Corinna Burger
    Department of Molecular Genetics and Microbiology, University of Florida, Gainesville 32610, USA
    Mol Ther 10:302-17. 2004
    ..Retrograde transport of rAAV1 and rAAV5 was also observed in particular CNS areas. These results suggest that vectors based on distinct AAV serotypes can be chosen for specific applications in the nervous system...
  13. pmc Next generation of adeno-associated virus 2 vectors: point mutations in tyrosines lead to high-efficiency transduction at lower doses
    Li Zhong
    Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA
    Proc Natl Acad Sci U S A 105:7827-32. 2008
    ..These studies have led to the development of AAV vectors that are capable of high-efficiency transduction at lower doses, which has important implications in their use in human gene therapy...
  14. ncbi Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors
    Sylvie Boutin
    Laboratoire d Immunologie, Genethon R and D, Evry Cedex, France
    Hum Gene Ther 21:704-12. 2010
    ..Better characterization of the preexisting humoral responses to the AAV capsid and cross-reactivity will allow development of new strategies to circumvent AAV acquired immune responses...
  15. pmc The 37/67-kilodalton laminin receptor is a receptor for adeno-associated virus serotypes 8, 2, 3, and 9
    Bassel Akache
    Stanford University, Department of Pediatrics, 300 Pasteur Drive, Room G305, Stanford, CA 94305 5208, USA
    J Virol 80:9831-6. 2006
    ..Along with its robust transduction efficiency, our findings support the continued development of AAV8-based vectors for clinical applications in humans, especially for tumor gene therapy...
  16. ncbi Intravenous scAAV9 delivery of a codon-optimized SMN1 sequence rescues SMA mice
    Elisa Dominguez
    UPMC AIM UMR S974, INSERM U 974, CNRS UMR 7215, Institut de Myologie, Universite Pierre et Marie Curie Paris 6, Paris, France
    Hum Mol Genet 20:681-93. 2011
    ..This study reports the most efficient rescue of SMA mice to date after a single intravenous injection of an optimized SMN-encoding scAAV9, highlighting the considerable potential of this method for the treatment of human SMA...
  17. pmc A viral assembly factor promotes AAV2 capsid formation in the nucleolus
    Florian Sonntag
    Department of Tumour Virology, German Cancer Research Center, D 69120 Heidelberg, Germany
    Proc Natl Acad Sci U S A 107:10220-5. 2010
    ..Sequence analysis suggests that also all other species of the genus Dependovirus encode a homologous protein in their cap gene...
  18. pmc Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN
    Kevin D Foust
    Center for Gene Therapy, The Research Institute at Nationwide Children s Hospital, Columbus, Ohio, USA
    Nat Biotechnol 28:271-4. 2010
    ..This demonstration that scAAV9 traverses the blood-brain barrier in a nonhuman primate emphasizes the clinical potential of scAAV9 gene therapy for SMA...
  19. pmc Dystrophin immunity in Duchenne's muscular dystrophy
    Jerry R Mendell
    Center for Gene Therapy, Research Institute at Nationwide Children s Hospital, Columbus, OH 43205, USA
    N Engl J Med 363:1429-37. 2010
    ..Funded by the Muscular Dystrophy Association and others; ClinicalTrials.gov number, NCT00428935.)...
  20. pmc Comparative cardiac gene delivery of adeno-associated virus serotypes 1-9 reveals that AAV6 mediates the most efficient transduction in mouse heart
    Carmela Zincarelli
    Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
    Clin Transl Sci 3:81-9. 2010
    ..Importantly, none of the serotypes tested with this marker gene affected cardiac function nor was associated with inflammation...
  21. pmc Robust systemic transduction with AAV9 vectors in mice: efficient global cardiac gene transfer superior to that of AAV8
    Katsuya Inagaki
    Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Mol Ther 14:45-53. 2006
    ..0 x 10(11) particles per mouse. Thus rAAV9, as well as rAAV8, is a robust vector for gene therapy applications and rAAV9 is superior to rAAV8 specifically for cardiac gene delivery by systemic vector administration...
  22. ncbi Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial
    Michael G Kaplitt
    Department of Neurological Surgery, Weill Medical College of Cornell University, New York, NY, USA
    Lancet 369:2097-105. 2007
    ..We aimed to measure the safety, tolerability, and potential efficacy of transfer of glutamic acid decarboxylase (GAD) gene with adeno-associated virus (AAV) into the subthalamic nucleus of patients with Parkinson's disease...
  23. ncbi CERE-110, an adeno-associated virus-based gene delivery vector expressing human nerve growth factor for the treatment of Alzheimer's disease
    Ronald J Mandel
    University of Florida, College of Medicine, Department of Neuroscience, PO Box 100244, Gainesville, FL 32610, USA
    Curr Opin Mol Ther 12:240-7. 2010
    ..CERE-110 has passed phase I clinical testing and a multicenter phase II clinical trial has commenced. CERE-110 is a promising candidate for the treatment of AD...
  24. pmc High-resolution labeling and functional manipulation of specific neuron types in mouse brain by Cre-activated viral gene expression
    Sandra J Kuhlman
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America
    PLoS ONE 3:e2005. 2008
    ....
  25. pmc Preclinical differences of intravascular AAV9 delivery to neurons and glia: a comparative study of adult mice and nonhuman primates
    Steven J Gray
    Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
    Mol Ther 19:1058-69. 2011
    ..Our results indicate that high peripheral tropism, limited neuronal transduction in NHPs, and pre-existing NAbs represent significant barriers to human translation of intravascular AAV9 delivery...
  26. pmc Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year
    Artur V Cideciyan
    Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Hum Gene Ther 20:999-1004. 2009
    ..The safety and efficacy of human retinal gene transfer with rAAV2-RPE65 vector extends to at least 1 year posttreatment...
  27. ncbi AAV-mediated hippocampal expression of short and long Homer 1 proteins differentially affect cognition and seizure activity in adult rats
    Matthias Klugmann
    Department of Molecular Medicine and Pathology, Functional Genomics and Translational Neuroscience Laboratory, University of Auckland, Auckland, New Zealand
    Mol Cell Neurosci 28:347-60. 2005
    ..Homer 1g induced anxiety. Moreover, AAV-Homer 1a animals showed attenuation of electrographic seizures in a model of status epilepticus. These results suggest that Homer 1 proteins play an active role in behavioral plasticity...
  28. pmc High-efficiency transduction of the mouse retina by tyrosine-mutant AAV serotype vectors
    Hilda Petrs-Silva
    Department of Ophthalmology, University of Florida, Gainesville, Florida 32610 0284, USA
    Mol Ther 17:463-71. 2009
    ..These enhanced AAV vectors have a great potential for future therapeutic applications for retinal degenerations and ocular neovascular diseases...
  29. pmc Optimizing promoters for recombinant adeno-associated virus-mediated gene expression in the peripheral and central nervous system using self-complementary vectors
    Steven J Gray
    Gene Therapy Center, University of North Carolina, Chapel Hill, NC 27599, USA
    Hum Gene Ther 22:1143-53. 2011
    ....
  30. pmc The AAV vector toolkit: poised at the clinical crossroads
    Aravind Asokan
    Gene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7352, USA
    Mol Ther 20:699-708. 2012
    ..This review will provide an overview of preclinical studies with the ever-expanding AAV vector portfolio in large animal models and an update on new lead AAV vector candidates poised for clinical translation...
  31. pmc Successful attenuation of humoral immunity to viral capsid and transgenic protein following AAV-mediated gene transfer with a non-depleting CD4 antibody and cyclosporine
    J H McIntosh
    Department of Haematology, UCL Cancer Institute, University College London, Oxford, UK
    Gene Ther 19:78-85. 2012
    ..These observations could significantly improve the prospects of using rAAV vectors for chronic disorders by allowing for repeated vector administration and avoiding the development of antibodies to the transgene product...
  32. ncbi Transduction characteristics of adeno-associated virus vectors expressing cap serotypes 7, 8, 9, and Rh10 in the mouse brain
    Cassia N Cearley
    W F Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, and Division of Neurology, Stokes Research Institute, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Mol Ther 13:528-37. 2006
    ..This facilitated the distribution of enzyme, resulting in correction of lysosomal storage lesions in regions of a diseased brain that would not be corrected if the genome were not transported...
  33. ncbi CD8(+) T-cell responses to adeno-associated virus capsid in humans
    Federico Mingozzi
    The Children s Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA
    Nat Med 13:419-22. 2007
    ..In addition, we show that AAV-2 induced human T cells proliferate upon exposure to alternate AAV serotypes, indicating that other serotypes are unlikely to evade capsid-specific immune responses...
  34. pmc Systemic gene delivery in large species for targeting spinal cord, brain, and peripheral tissues for pediatric disorders
    Adam K Bevan
    Center for Gene Therapy, The Research Institute at Nationwide Children s Hospital, Columbus, Ohio 43205, USA
    Mol Ther 19:1971-80. 2011
    ..Our findings support the use of AAV9 for gene transfer to the CNS for disorders in pediatric populations...
  35. pmc Engineering of human pluripotent stem cells by AAV-mediated gene targeting
    Iram F Khan
    Department of Medicine, University of Washington, Seattle, Washington 98195, USA
    Mol Ther 18:1192-9. 2010
    ..Accurate and efficient targeting took place with minimal or no cytotoxicity, and most of the gene-targeted stem cells produced were euploid and pluripotent...
  36. ncbi Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model
    Brian K Kaspar
    Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Science 301:839-42. 2003
    ..We report that insulin-like growth factor 1 prolongs life and delays disease progression, even when delivered at the time of overt disease symptoms...
  37. ncbi New recombinant serotypes of AAV vectors
    Guangping Gao
    Division of Medical Genetics, Department of Medicine, University of Pennsylvania School of Medicine, 2000, Translational Research Laboratories, 125S, 31st Street, Philadelphia, PA 19104 3403, USA
    Curr Gene Ther 5:285-97. 2005
    ..Vectors based on new primate AAVs could become the next generation of efficient gene transfer vehicles for various gene therapy applications...
  38. ncbi Self-complementary AAV vectors; advances and applications
    Douglas M McCarty
    Center for Gene Therapy, The Research Institute at Nationwide Children s Hospital, The Ohio State University, Columbus, Ohio 43205, USA
    Mol Ther 16:1648-56. 2008
    ..Along with the construction and physical properties of self-complementary vectors, the basis of the varying responses in multiple tissues including liver, muscle, and central nervous system (CNS) will be explored in this review...
  39. ncbi Recombinant adeno-associated virus serotype 9 leads to preferential cardiac transduction in vivo
    Christina A Pacak
    Center for Fetal Monkey Gene Transfer for Heart, Lung and Blood Diseases, California National Primate Research Center, Davis, USA
    Circ Res 99:e3-9. 2006
    ....
  40. ncbi Real-time single-molecule imaging of the infection pathway of an adeno-associated virus
    G Seisenberger
    Department Chemie, , Butenandtstrasse 11, , Germany
    Science 294:1929-32. 2001
    ..The real-time visualization of the infection pathway of single AAVs shows a much faster infection than was generally observed so far...
  41. pmc The genome of self-complementary adeno-associated viral vectors increases Toll-like receptor 9-dependent innate immune responses in the liver
    Ashley T Martino
    Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA
    Blood 117:6459-68. 2011
    ..Increased innate responses to scAAV correlated with stronger adaptive immune responses against capsid (but not against the transgene product). However, these could be blunted by transient inhibition of TLR9...
  42. ncbi Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis
    D M McCarty
    UNC Gene Therapy Center, University of North Carolina at Chapel Hill, NC, USA
    Gene Ther 8:1248-54. 2001
    ..These novel scAAV vectors represent a biochemical intermediate in rAAV transduction and should provide new insights into the biology of vector transduction...
  43. pmc AAV8, 9, Rh10, Rh43 vector gene transfer in the rat brain: effects of serotype, promoter and purification method
    Ronald L Klein
    Department of Pharmacology, Toxicology, and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA
    Mol Ther 16:89-96. 2008
    ..The purification method can therefore impact the transduction pattern as well as the results when comparing serotype strengths...
  44. ncbi Exchange of surface proteins impacts on viral vector cellular specificity and transduction characteristics: the retina as a model
    A Auricchio
    Institute for Human Gene Therapy, Department of Molecular and Cellular Engineering, The Wistar Institute, Philadelphia, PA, USA
    Hum Mol Genet 10:3075-81. 2001
    ..We conclude that pseudotyping provides a useful means to manipulate viral vector cell targeting specificity as well as retinal transduction characteristics of vectors containing the same genome...
  45. ncbi Schwann cell targeting via intrasciatic injection of AAV8 as gene therapy strategy for peripheral nerve regeneration
    J Homs
    Center of Animal Biotechnology and Gene Therapy, Universitat Autonoma de Barcelona, Barcelona, Spain
    Gene Ther 18:622-30. 2011
    ..These results prove the utility of AAV8 as a gene therapy vector for Schwann cells to treat myelin disorders or to improve nerve regeneration...
  46. pmc Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease
    Vanesa Sanchez-Guajardo
    Central Nervous System Disease Modeling Group, Department of Medical Biochemistry, Aarhus University, Aarhus, Denmark
    PLoS ONE 5:e8784. 2010
    ..Furthermore, our data suggest that the microglial response is modulated by early events related to alpha-syn expression in substantia nigra and persists at the long term...
  47. pmc Adeno-associated virus serotype 4 (AAV4) and AAV5 both require sialic acid binding for hemagglutination and efficient transduction but differ in sialic acid linkage specificity
    N Kaludov
    Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA
    J Virol 75:6884-93. 2001
    ..These results suggest that AAV4 and AAV5 require different sialic acid-containing glycoproteins for binding and transduction of target cells and they further explain the different tropism of AAV4 and AAV5...
  48. pmc Adeno-associated virus serotype 6 capsid tyrosine-to-phenylalanine mutations improve gene transfer to skeletal muscle
    Chunping Qiao
    Division of Molecular Pharmaceutics, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC 27599, USA
    Hum Gene Ther 21:1343-8. 2010
    ..Our results suggest that tyrosine-mutant AAV6 vectors may represent powerful tools for testing muscle gene therapy in animal models and potentially in humans...
  49. pmc Adeno-associated viruses undergo substantial evolution in primates during natural infections
    Guangping Gao
    Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
    Proc Natl Acad Sci U S A 100:6081-6. 2003
    ..This is an example of rapid molecular evolution of a DNA virus in a way that was formerly thought to be restricted to RNA viruses...
  50. pmc Long-term retinal function and structure rescue using capsid mutant AAV8 vector in the rd10 mouse, a model of recessive retinitis pigmentosa
    Ji Jing Pang
    Eye Hospital, School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang, China
    Mol Ther 19:234-42. 2011
    ..These results lay the groundwork for the development of PDEβ-RP gene therapy trial and suggest that tyrosine-capsid mutant AAV vectors may be effective for treating other rapidly degenerating models of retinal degeneration...
  51. ncbi Intracellular transport of recombinant adeno-associated virus vectors
    M Nonnenmacher
    Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY 10029, USA
    Gene Ther 19:649-58. 2012
    ....
  52. pmc Convection-enhanced delivery and systemic mannitol increase gene product distribution of AAV vectors 5, 8, and 9 and increase gene product in the adult mouse brain
    Nikisha Carty
    Byrd Alzheimer s Institute and Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine, Tampa, FL 33613, USA
    J Neurosci Methods 194:144-53. 2010
    ..These data suggest that combining advanced injection techniques with newer rAAV serotypes greatly improves viral vector distribution, which could have significant benefits for implementation of gene therapy strategies...
  53. pmc A simplified baculovirus-AAV expression vector system coupled with one-step affinity purification yields high-titer rAAV stocks from insect cells
    Richard H Smith
    Laboratory of Biochemical Genetics, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA
    Mol Ther 17:1888-96. 2009
    ..Using the described method, we obtained an average yield of 7 x 10(4) purified rAAV particles per cell (range: 3.7 x 10(4) to 9.6 x 10(4)) from suspension cultures of recombinant baculovirus-infected insect cells...
  54. pmc Epidermal growth factor receptor is a co-receptor for adeno-associated virus serotype 6
    Melodie L Weller
    Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, US National Institutes of Health NIH, Bethesda, Maryland, USA
    Nat Med 16:662-4. 2010
    ..Subsequent experiments suggested that EGFR is necessary for vector internalization and probably functions as a co-receptor for AAV6...
  55. pmc Characterization of a recombinant adeno-associated virus type 2 Reference Standard Material
    Martin Lock
    Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Hum Gene Ther 21:1273-85. 2010
    ..The rAAV2 RSM has been deposited with the American Type Culture Collection and is available to the scientific community to calibrate laboratory-specific internal titer standards. Anticipated uses of the rAAV2 RSM are discussed...
  56. ncbi Comparison of adeno-associated viral vector serotypes for spinal cord and motor neuron gene delivery
    Brooke R Snyder
    Department of Neurosurgery, Emory University, Atlanta, GA 30322, USA
    Hum Gene Ther 22:1129-35. 2011
    ..In summary, intrathecal delivery of AAV6 or AAV9 vectors containing the CMV promoter yielded the strongest levels of biodistribution and MN transduction in the spinal cord...
  57. pmc AAV-mediated photoreceptor transduction of the pig cone-enriched retina
    C Mussolino
    Telethon Institute of Genetics and Medicine, Naples, Italy
    Gene Ther 18:637-45. 2011
    ..The data presented here on AAV-mediated transduction of the cone-enriched porcine retina may affect the development of gene-based therapies for rare and common severe photoreceptor diseases...
  58. ncbi Gene targeting in human pluripotent stem cells with adeno-associated virus vectors
    Kaoru Mitsui
    Gene Therapy Division, Research Center for Genomic Medicine, Saitama Medical University, 1397 1 Yamane, Hidaka, Saitama 350 1241, Japan
    Biochem Biophys Res Commun 388:711-7. 2009
    ..In addition to hESC, gene targeting was achieved in hiPSC lines at similar frequencies. These data indicate that AAV vectors may therefore be a useful tool to introduce genetic modifications in hESCs and hiPSCs...
  59. pmc Novel adeno-associated virus serotypes efficiently transduce murine photoreceptors
    Mariacarmela Allocca
    Telethon Institute of Genetics and Medicine, Via P Castellino 111, 80131 Napoli, Italy
    J Virol 81:11372-80. 2007
    ....
  60. pmc Novel AAV serotypes for improved ocular gene transfer
    Corinna Lebherz
    Gene Therapy Program, Division of Medical Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    J Gene Med 10:375-82. 2008
    ..We show here that AAV7 and 8 enable superior long-term transduction of retinal and also anterior chamber structures...
  61. pmc The TLR9-MyD88 pathway is critical for adaptive immune responses to adeno-associated virus gene therapy vectors in mice
    Jiangao Zhu
    Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Clin Invest 119:2388-98. 2009
    ....
  62. pmc Preferential labeling of inhibitory and excitatory cortical neurons by endogenous tropism of adeno-associated virus and lentivirus vectors
    J L Nathanson
    Systems Neurobiology Laboratories, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Neuroscience 161:441-50. 2009
    ..These findings demonstrate that endogenous tropism of rAAV2/1 and VSV-G-LV can be used to obtain preferential gene expression in mouse somatosensory cortical inhibitory and excitatory neuron populations, respectively...
  63. ncbi Production and characterization of adeno-associated viral vectors
    Joshua C Grieger
    Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Nat Protoc 1:1412-28. 2006
    ..This review provides an up-to-date, detailed description of essential methods such as production, purification and titering and their application to characterize current AAV vectors for preclinical and clinical use...
  64. ncbi Gene therapy restores vision in a canine model of childhood blindness
    G M Acland
    James A Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
    Nat Genet 28:92-5. 2001
    ..Our results indicate that visual function was restored in this large animal model of childhood blindness...
  65. ncbi Expression of shRNA from a tissue-specific pol II promoter is an effective and safe RNAi therapeutic
    Jeffery C Giering
    Department of Pediatrics, Stanford University, Stanford, California 94305, USA
    Mol Ther 16:1630-6. 2008
    ....
  66. ncbi Intracranial adeno-associated virus-mediated delivery of anti-pan amyloid beta, amyloid beta40, and amyloid beta42 single-chain variable fragments attenuates plaque pathology in amyloid precursor protein mice
    Yona Levites
    Department of Neuroscience, Mayo Clinic, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
    J Neurosci 26:11923-8. 2006
    ..As opposed to transgenic approaches, these studies also establish a "somatic brain transgenic" paradigm to rapidly and cost-effectively evaluate potential modifiers of AD-like pathology in AD mouse models...
  67. ncbi Induction of functional neovascularization by combined VEGF and angiopoietin-1 gene transfer using AAV vectors
    Nikola Arsic
    Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy
    Mol Ther 7:450-9. 2003
    ..Co-expression of VEGF165 with angiopoietin-1-which did not display angiogenic effect per se-remarkably reduced leakage of vessels produced by VEGF165 alone...
  68. pmc Activation of the NF-kappaB pathway by adeno-associated virus (AAV) vectors and its implications in immune response and gene therapy
    Giridhara R Jayandharan
    Division of Cellular and Molecular Therapy, Department of Pediatrics, Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32611, USA
    Proc Natl Acad Sci U S A 108:3743-8. 2011
    ....
  69. pmc Adeno-associated virus (AAV) serotype 9 provides global cardiac gene transfer superior to AAV1, AAV6, AAV7, and AAV8 in the mouse and rat
    Lawrence T Bish
    Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Hum Gene Ther 19:1359-68. 2008
    ..AAV9 should be used in rodent cardiac studies and may be the vector of choice for clinical trials of cardiac gene transfer...
  70. ncbi Insect cells as a factory to produce adeno-associated virus type 2 vectors
    Masashi Urabe
    Laboratory of Biochemical Genetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Hum Gene Ther 13:1935-43. 2002
    ..This robust system provides a simple, cost-effective method for AAV vector production...
  71. pmc Intraventricular brain injection of adeno-associated virus type 1 (AAV1) in neonatal mice results in complementary patterns of neuronal transduction to AAV2 and total long-term correction of storage lesions in the brains of beta-glucuronidase-deficient mi
    Marco A Passini
    Department of Pathobiology and Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Virol 77:7034-40. 2003
    ....
  72. pmc Adeno-associated virus serotype-9 efficiently transduces the retinal outer plexiform layer
    Bo Lei
    Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Yu Zhong District, Chongqing, China
    Mol Vis 15:1374-82. 2009
    ..Adeno-associated virus serotype-9 (AAV-9) is a promising gene delivery vector. In this study, we evaluated AAV-9 transduction in the mouse retina...
  73. pmc Alpha2,3 and alpha2,6 N-linked sialic acids facilitate efficient binding and transduction by adeno-associated virus types 1 and 6
    Zhijian Wu
    Gene Therapy Center, CB 7352, 7119 Thurston Building, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7352, USA
    J Virol 80:9093-103. 2006
    ....
  74. pmc Intrastriatal rAAV-mediated delivery of anti-huntingtin shRNAs induces partial reversal of disease progression in R6/1 Huntington's disease transgenic mice
    Edgardo Rodriguez-Lebron
    Department of Neuroscience, University of Florida McKnight Brain Institute, Gainesville, 32610 0244, USA
    Mol Ther 12:618-33. 2005
    ..These results suggest that a reduction in the levels of striatal mHtt can ameliorate the HD phenotype of R6/1 mice...
  75. pmc Enhancement of adeno-associated virus infection by mobilizing capsids into and out of the nucleolus
    Jarrod S Johnson
    Gene Therapy Center and Department of Pharmacology, The University of North Carolina at Chapel Hill, 7119 Thurston Bowles, CB 7352, Chapel Hill, North Carolina 27599 7352, USA
    J Virol 83:2632-44. 2009
    ..In summary, with these studies we have refined our understanding of AAV2 trafficking dynamics and have identified cellular parameters that mobilize virions in the nucleus and significantly influence AAV infection...
  76. pmc Gene therapy for retinitis pigmentosa and Leber congenital amaurosis caused by defects in AIPL1: effective rescue of mouse models of partial and complete Aipl1 deficiency using AAV2/2 and AAV2/8 vectors
    Mei Hong Tan
    Institute of Ophthalmology, NIHR Biomedical Research Centre, University College London, London, UK
    Hum Mol Genet 18:2099-114. 2009
    ..This is the first gene replacement study to report long-term rescue of a photoreceptor-specific defect and to demonstrate effective rescue of a rapid photoreceptor degeneration...
  77. pmc Changes in adeno-associated virus-mediated gene delivery in retinal degeneration
    Kathleen D Kolstad
    Department of Molecular and Cellular Biology and Helen Wills Neuroscience Institute, University of California at Berkeley, Berkeley, CA 94720 3190, USA
    Hum Gene Ther 21:571-8. 2010
    ..Furthermore, these results indicate that gene delivery to the outer nuclear layer may be achieved by noninvasive intravitreal AAV administration in the diseased state...
  78. pmc Cell-type-specific characteristics modulate the transduction efficiency of adeno-associated virus type 2 and restrain infection of endothelial cells
    Katri Pajusola
    Institute of Molecular Biology, University of Zurich, 8057 Zurich, Switzerland
    J Virol 76:11530-40. 2002
    ..Accordingly, in endothelial cells detached from their matrix, AAV-2 transduction was significantly increased. Altogether, these results point to a more complex cell-type-specific mode of transduction of AAV-2 than previously appreciated...
  79. pmc H2AX is required for cell cycle arrest via the p53/p21 pathway
    Michalis Fragkos
    Ecole Polytechnique Federale de Lausanne, Faculty of Life Sciences, Swiss Institute for Experimental Cancer Research, 1015 Lausanne, Switzerland
    Mol Cell Biol 29:2828-40. 2009
    ..The results establish a new role for H2AX in the p53/p21 pathway and indicate that H2AX is required for p21-induced cell cycle arrest after replication stalling...
  80. ncbi Intracellular trafficking of adeno-associated viral vectors
    W Ding
    Department of Anatomy and Cell Biology, University of Iowa School of Medicine, Iowa City, 52242, USA
    Gene Ther 12:873-80. 2005
    ..Advances in understanding this area of rAAV biology will help to improve the efficacy of this vector system for the treatment of inherited and acquired diseases...
  81. ncbi Recombinant adeno-associated virus serotype 4 mediates unique and exclusive long-term transduction of retinal pigmented epithelium in rat, dog, and nonhuman primate after subretinal delivery
    Michel Weber
    Laboratoire de Thérapie Génique, INSERM ERM01 05, CHU Hotel Dieu, Bât J Monnet, 30 Avenue J Monnet, 44035, Nantes Cedex 01, France
    Mol Ther 7:774-81. 2003
    ..Overall, these findings will have a practical impact on the development of future gene therapy trials of retinal diseases...
  82. pmc Restoration of cone vision in the CNGA3-/- mouse model of congenital complete lack of cone photoreceptor function
    Stylianos Michalakis
    Center for Integrated Protein Science Munich CIPSM, Department of Pharmacy Center for Drug Research, Ludwig Maximilians Universitat Munchen, Munich, Germany
    Mol Ther 18:2057-63. 2010
    ..Finally, we demonstrate that this newly acquired sensory information was translated into cone-mediated, vision-guided behavior...
  83. pmc High-efficiency transduction and correction of murine hemophilia B using AAV2 vectors devoid of multiple surface-exposed tyrosines
    David M Markusic
    Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida 32611, USA
    Mol Ther 18:2048-56. 2010
    ..Such vectors should be attractive for treatment of hemophilia and other genetic diseases...
  84. ncbi Differential transgene expression in brain cells in vivo and in vitro from AAV-2 vectors with small transcriptional control units
    S Kugler
    Department of Neurology, University of Gottingen, Medical School S2 Laboratory, Waldweg 33, 37073, Gottingen, Germany
    Virology 311:89-95. 2003
    ..We propose that neuron specific transgene expression in combination with enhanced transgene capacity will further substantially improve AAV based vector technology...
  85. pmc Production of CFTR-null and CFTR-DeltaF508 heterozygous pigs by adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer
    Christopher S Rogers
    Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
    J Clin Invest 118:1571-7. 2008
    ..In addition, because gene-modified mice often fail to replicate human diseases, this approach could be used to generate models of other human genetic diseases in species other than mice...
  86. ncbi Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses
    Roberto Calcedo
    Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Infect Dis 199:381-90. 2009
    ..33 was only rarely detected. Our data also indicate a strong linkage of seroreactivity between apparently distinct serotypes that has not been predicted previously in animal models...
  87. pmc A single intravenous injection of adeno-associated virus serotype-9 leads to whole body skeletal muscle transduction in dogs
    Yongping Yue
    Department of Molecular Microbiology and Immunology, School of Medicine, The University of Missouri, Columbia, Missouri 65212, USA
    Mol Ther 16:1944-52. 2008
    ..In particular, cardiac muscle was barely transduced in dogs. Many muscular dystrophy patients can be identified by neonatal screening. The technology described here may lead to an effective early intervention in these patients...
  88. ncbi The mutant human ND4 subunit of complex I induces optic neuropathy in the mouse
    Xiaoping Qi
    Department of Ophthalmology, University of Florida College of Medicine, Gainesville, FL 32610 0284, USA
    Invest Ophthalmol Vis Sci 48:1-10. 2007
    ..To produce a mouse model of Leber hereditary optic neuropathy...
  89. ncbi Stereotaxic gene delivery in the rodent brain
    Ali Cetin
    Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany
    Nat Protoc 1:3166-73. 2006
    ..The entire protocol can be completed in 1-2 hours...
  90. ncbi Long-term inhibition of glycosphingolipid accumulation in Fabry model mice by a single systemic injection of AAV1 vector in the neonatal period
    Koichi Ogawa
    Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan
    Mol Genet Metab 96:91-6. 2009
    ..Neonatal injection is effective to inhibit Gb3 accumulation and therefore, might help prevent failure of major organs during adulthood...
  91. pmc Adeno-associated virus gene repair corrects a mouse model of hereditary tyrosinemia in vivo
    NICOLE K PAULK
    Oregon Stem Cell Center, Oregon Health and Science University, Portland, OR 97203, USA
    Hepatology 51:1200-8. 2010
    ..In this model, repaired hepatocytes have a selective growth advantage and are thus able to proliferate to efficiently repopulate mutant livers and cure the underlying metabolic disease...
  92. pmc Correction of neurological disease of mucopolysaccharidosis IIIB in adult mice by rAAV9 trans-blood-brain barrier gene delivery
    Haiyan Fu
    The Center for Gene Therapy, The Research Institute at Nationwide Children s Hospital, Columbus, Ohio 43205, USA
    Mol Ther 19:1025-33. 2011
    ..These data suggest promising clinical potential using the trans-BBB neurotropic rAAV9 vector for treating MPS IIIB and other neurogenetic diseases...
  93. ncbi Dimerizer regulation of AADC expression and behavioral response in AAV-transduced 6-OHDA lesioned rats
    Laura M Sanftner
    Avigen, Inc, 1301 Harbor Bay Parkway, Alameda, CA 94502, USA
    Mol Ther 13:167-74. 2006
    ..Recombinant AAV vectors controlled by rapamycin or its analogs show promise as candidates for CNS therapies in which regulation of the transgene is desired...
  94. ncbi AAV vector-mediated reversal of hypoglycemia in canine and murine glycogen storage disease type Ia
    Dwight D Koeberl
    Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Ther 16:665-72. 2008
    ..These preclinical data demonstrated the efficacy of correcting hepatic G6Pase deficiency, and support the further preclinical development of AAV vector-mediated gene therapy for GSD-Ia...
  95. pmc Therapeutic neonatal hepatic gene therapy in mucopolysaccharidosis VII dogs
    Katherine Parker Ponder
    Departments of Internal Medicine and Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 99:13102-7. 2002
    ..This is the first successful application of gene therapy in preventing the clinical manifestations of a lysosomal storage disease in a large animal...
  96. pmc Disease rescue and increased lifespan in a model of cardiomyopathy and muscular dystrophy by combined AAV treatments
    Carmen Vitiello
    Telethon Institute of Genetics and Medicine TIGEM, Naples, Italy
    PLoS ONE 4:e5051. 2009
    ..The muscle disease is progressive and average lifespan is 11 months, because heart slowly dilates towards heart failure...
  97. pmc Controlling neuropathic pain by adeno-associated virus driven production of the anti-inflammatory cytokine, interleukin-10
    Erin D Milligan
    Department of Psychology and the Center for Neuroscience, University of CO at Boulder, Boulder, CO 80309 USA
    Mol Pain 1:9. 2005
    ..Taken together, these data provide initial support that intrathecal gene therapy to drive the production of IL-10 may prove to be an efficacious treatment for neuropathic pain...
  98. ncbi Versatility of AAV vectors for retinal gene transfer
    Enrico M Surace
    Telethon Institute of Genetics and Medicine, Naples, Italy
    Vision Res 48:353-9. 2008
    ..The results from the forthcoming trials with AAV in the retina of patients with Leber Congenital Amaurosis will be critical for the rapid development of AAV-based therapeutics for retinal diseases...
  99. ncbi Long-term inducible gene expression in the eye via adeno-associated virus gene transfer in nonhuman primates
    Corinna Lebherz
    Gene Therapy Program, Department of Medicine, Division of Medical Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA
    Hum Gene Ther 16:178-86. 2005
    ..5 years. The expression profiles were characterized by minimal basal expression in the absence of inducer and dose-responsive maximal expression in the presence of inducer drug...
  100. pmc Differential activation of innate immune responses by adenovirus and adeno-associated virus vectors
    Anne Kathrin Zaiss
    Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta T2N 4N1, Canada
    J Virol 76:4580-90. 2002
    ....
  101. pmc High-level transgene expression in nonhuman primate liver with novel adeno-associated virus serotypes containing self-complementary genomes
    Guang Ping Gao
    Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 3403, USA
    J Virol 80:6192-4. 2006
    ..Analysis of DNAs from tissues revealed high levels of vector in the liver that appeared proportional to the relative amounts of transgene expression...

Research Grants73

  1. NIH Director's Pioneer Award
    ERICH JARVIS; Fiscal Year: 2009
    ..Repairing the pathway in vocal learners, when damaged, would have profound impact for correcting neurological disorders of speech. ..
  2. Ethanol Regulation of Serum Glucocorticoid Kinase I
    BLAIR N COSTIN; Fiscal Year: 2012
    ..The work proposed here could shed light on molecular mechanisms underlying alcoholism and eventually have implications in the development of novel pharmacological agents for alcoholism or alcohol-related neurological disorders. ..
  3. Gene Therapy with Cardiotropic Vectors for the Treatment of Heart Failure
    Roger J Hajjar; Fiscal Year: 2013
    ....
  4. Role of Potent Trophic Factors on Glia and Motor Neurons in ALS
    Brian K Kaspar; Fiscal Year: 2013
    ..We will subsequently test the optimal combination of these factors using gene delivery in a rodent model of this devastating disease in order to define an optimal therapy for this debilitating disorder. ..
  5. CTL response to AAV Vector
    Richard J Samulski; Fiscal Year: 2013
    ....
  6. RNA interference therapy for Huntington's disease: studies in non-human primates
    Beverly L Davidson; Fiscal Year: 2010
    ..This work is a collaborative effort between laboratories at the University of Iowa and the Oregon National Primate Research Center at the Oregon Health Sciences University. ..
  7. Testing the efficacy of PGC-1alpha as a therapeutic target for Parkinson's diseas
    HANS BUELER; Fiscal Year: 2010
    ..abstract_text> ..
  8. Leptin function &resistance in midbrain VTA &SN in reward eating &obesity
    YI NONE ZHANG; Fiscal Year: 2013
    ..The long-range benefit from our study would be to reduce the ever-rising burden of long-term health care costs within the VA patient care system. ..
  9. Gene-Engineered and Targeted Stem Cell Therapy for Myeloma
    Selvarangan Ponnazhagan; Fiscal Year: 2013
    ..Successful completion of these studies will allow us to initiate phase-1 human clinical trials. ..
  10. Gene Therapy for Retinitis Pigmentosa
    Rajendra Kumar-Singh; Fiscal Year: 2012
    ..that are collectively the most common causes of blindness in the United States. ..
  11. Modeling schizophrenia gamma deficits using cell-specific RNAi knockdown of GAD67
    RITCHIE EDWARD BROWN; Fiscal Year: 2012
    ....
  12. Novel therapy for monoamine neurotransmitter deficiency in PKU
    Cary O Harding; Fiscal Year: 2013
    ..Our goal is to thoroughly evaluate these novel therapeutic approaches in Pahenu2 mice and to choose specific interventions for a future clinical trial in humans with PKU. ..
  13. MECHANISMS OF MALADAPTATION IN HEART FAILURE
    Howard A Rockman; Fiscal Year: 2013
    ..Furthermore, the proposed studies will lead to new targets to treat cardiac hypertrophy and heart failure in humans. ..
  14. Regulated Transgene Expression in the Retina
    James M Wilson; Fiscal Year: 2010
    ....
  15. Role of Stasimon Dysfunction in Spinal Muscular Atrophy
    Livio Pellizzoni; Fiscal Year: 2013
    ..Collectively, these experiments have the potential to identify Stasimon as a downstream target of SMN dysfunction that contributes to SMA pathology in a mouse model of this devastating human disease. ..
  16. Effects of ozone exposure on expression and function of surfactant protein D
    Angela Haczku; Fiscal Year: 2010
    ..Results from this application will define the implications of SP-D in O3-induced exacerbation of asthma and will provide novel approaches to manipulate the pulmonary immune system. ..
  17. Gene therapy in the cornea
    RAJIV RAVINDRA MOHAN; Fiscal Year: 2012
    ..Targeted gene therapy delivered to the cornea with a simple topical technique offers promise to cure, treat and/or prevent vision loss by modulating excessive healing mechanisms that cause these blinding corneal disorders. ..
  18. Control of Breathing and Pompe Disease
    David D Fuller; Fiscal Year: 2013
    ..This renewal application targets optimization of adeno-associated virus (AAV) based therapies to treat respiratory neurons in Pompe disease. ..
  19. c-Myc transcription in intestinal growth, differentiation, and carcinogenesis
    Gregory S Yochum; Fiscal Year: 2012
    ..Our studies address the fundamental mechanisms underlying b-catenin regulation of normal gastrointestinal development and homeostasis as well as the pathogenesis of intestinal malignancy. ..
  20. Inflammation and Oxidative Stress in Parkinsons Disease
    Paula C Bickford; Fiscal Year: 2013
    ..If these therapies have significant clinical potential this will be a step forward for Parkinsons therapeutics. ..
  21. Role of complement in alpha-synuclein based models of Parkinson disease
    HEATHER ELIZABETH ALLEN; Fiscal Year: 2013
    ..This proposal aims to provide evidence for a role for the complement system in PD pathology. This study would serve as rationale for the complement system as an innovative target for the development of PD therapies and biomarkers. ..
  22. AAV vectors for retinal delivery in a mouse model of age-related retinopathy
    KATHARINE LIANG; Fiscal Year: 2013
    ..The proposed training and research plans will provide a solid educational and professional foundation on which to pursue a career as a physician scientist in the field of translational Ophthalmology. ..
  23. TBI epileptogenesis: pathologic hippocampal L-glut synaptic plasticity
    John T Slevin; Fiscal Year: 2011
    ....
  24. Dual AAV Vectors for Duchenne Muscular Dystrophy Therapy
    Dongsheng Duan; Fiscal Year: 2012
    ..Our findings will pave the way to eventually move dual AAV gene therapy to human trials in the future. ..
  25. Viral Gene Expression to Therapeutic Levels in Models of Heart Failure
    Joseph E Rabinowitz; Fiscal Year: 2012
    ..An end point for this application is to determine the therapeutic dose of a therapeutic gene delivered by an experimental gene transfer vector. ..
  26. Towards a Model of Fanconi Anemia
    BEVERLY JO TOROK STORB; Fiscal Year: 2010
    ..We plan to optimize the methods for culture, genetic manipulation, and transplantation of SSC in dogs, and to use this technology to set the stage for producing a canine model of Fanconi Anemia. ..
  27. Novel Protective Antiapoptotic Action of Alpha 1-Antitrypsin In Emphysema
    Rubin M Tuder; Fiscal Year: 2011
    ..abstract_text> ..
  28. Neuroprotective role of RAB3B in rodent models of Parkinson's disease
    Chee Yeun Chung; Fiscal Year: 2010
    ..Our goal in this grant is to characterize the neuroprotective role of RAB3B in two different rodent models of Parkinson's disease. ..
  29. Neuron-specific block of T-type calcium channels
    Edward Perez-Reyes; Fiscal Year: 2012
    ..The research team includes Dr. Edward Perez- Reyes, a T-channel expert, Dr. Guanping Gao, an AAV expert, and Dr. Hui-Lin Pan, a neuropathic pain expert. ..
  30. Novel Adeno-Associated Viral Therapy for Wet Age-Related Macular Degeneration
    James M Wilson; Fiscal Year: 2012
    ....
  31. Diabetes Erectile dysfunction and apoptosis of cavernous tissues
    Rajvir Dahiya; Fiscal Year: 2010
    ..Accomplishment of these experiments will provide novel molecular mechanisms of erectile dysfunction and can help guide us towards the development of new therapies for the treatment of erectile dysfunction. ..
  32. Defining a clinically relevant time point for astrocyte targeted therapy in ALS
    Brian K Kaspar; Fiscal Year: 2013
    ..This work will generate important insights to unravel the optimal therapeutic time window for attenuating aberrant glial cell toxicity in ALS providing the basis for a translational approach to remove mtSOD1 in patients. ..
  33. Phase 2 Study of rAAV1-CB-hAAT for Treatment of Alpha-1 Antitrypsin Deficiency
    Jeffrey D Chulay; Fiscal Year: 2013
    ..Results from this Phase 2 trial will be used to develop a Phase 3 study designed to satisfy the requirements for licensure of a gene therapy treatment for this orphan disease. ..
  34. Novel Adeno-Associated Viral Therapy for X-linked Retinitis Pigmentosa
    James M Wilson; Fiscal Year: 2010
    ..This proposal is designed to develop a gene therapeutic that will provide significant medical relief to patients, develop technologies applicable to other indications in the eye, and minimize the burden on the healthcare system. ..
  35. FAH-Deficient Pigs
    Scott L Nyberg; Fiscal Year: 2011
    ..Thus the demand for these new pigs is worthy of commercialization. ..
  36. Glioma immunotherapy with strategies based on autonomous parvovirus MVMp
    JUSTIN COBB PAGLINO; Fiscal Year: 2013
    ..In Aim 2 I test two parvoviral vectors expressing cytokines. In Aim 3 I test an 'altere self epitope library'engineered into parvoviral vector. I look forward to the research and trainin activities described herein. ..
  37. Development of a human Oct-4 gene-targeted reporter cell line
    GREGORY LENO; Fiscal Year: 2010
    ..Efficiently reprogrammed human cells have viable commercial applications in regenerative medicine. ..
  38. Translating CNS therapies for the NCLs from rodent models to humans
    Beverly L Davidson; Fiscal Year: 2010
    ....
  39. Gene enhanced cartilage repair in a cytokine permissive environment
    Alan J Nixon; Fiscal Year: 2012
    ..Insulin-like growth factor-I (IGF-I) enhances cartilage repair and this grant tests long-term growth factor expression in joints where degradation is controlled by RNA interference. ..
  40. Role of Calcium-Activated Chloride Channels in Airway Disease Phenotypes
    ANAND CHAMPAK PATEL; Fiscal Year: 2011
    ..These proposed experiments should serve to define CLCA function in experimental asthma and thereby provide for new therapeutic targets in humans with airway disease. ..
  41. Molecular Evolution Strategies to Derive New Recombinant AAV Vectors
    Mark A Kay; Fiscal Year: 2012
    ..Once the new AAV vectors are created, they will be tested in animal models of human disease. ..
  42. Novel Vaginal Microbicides Based On Stable AAV-Neutralizing Antibody Gene Transfe
    Wayne A Marasco; Fiscal Year: 2010
    ..A protective genetic microbicide delivered to the female lower genital track could dramatically slow the spread of HIV/AIDS. ..
  43. GE Healthcare Fast Protein Liquid Chromatography FPLC product number 13470501.
    Jasti S Rao; Fiscal Year: 2010
    ..To date, however, no satisfactory treatments are available for either AD or many cancers making further research vitally important for human welfare. ..
  44. Screens for host DNA replication and repair factors involved in viral infection
    Matthew D Weitzman; Fiscal Year: 2010
    ..These screens will identify cellular factors that regulate viral infection, will provide insights into virus-host interactions and fundamental cellular processes, and may suggest targets for anti-viral therapies. ..
  45. VGF function in depression and antidepressant treatment
    Stephen R Salton; Fiscal Year: 2013
    ....
  46. Modification of AdenoAssociated Virus to deliver DNA directly to Mitochondria
    John Guy; Fiscal Year: 2011
    ..We will share the vector with other groups whose goal it is to treat these disorders. ..
  47. Histone Deacetylases: Regulators of Cocaine Reward and Targets for Therapeutics
    MARCELO ANDRES WOOD; Fiscal Year: 2012
    ..In summary, this research proposal describes an innovative genetic and pharmacological approach to examine the role of a key HDAC, HDAC3, in acquisition and extinction of drug-seeking behavior. ..
  48. PTEN Gene Therapy for Vein Graft Disease
    Christopher D Kontos; Fiscal Year: 2010
    ..The results of these studies may have a substantial impact on outcomes for patients requiring venous bypass grafting and AVF placement. ..
  49. Investigating the RhoA/ROCK pathway for the treatment of Alzheimer's disease
    JEREMY HARTFORD HERSKOWITZ; Fiscal Year: 2013
    ....
  50. Exosome based therapeutics in Huntington's disease
    Neil Aronin; Fiscal Year: 2013
    ..Harnessing exosomes for brain delivery is expected to form a viable therapeutic to reduce expression of mutant huntingtin in patients with HD. Patients with other genetically- based neurodegeneration will benefit. ..
  51. Ultrasound-Assisted AQP1 Gene Therapy for Functional Restoration of Salivary Glan
    Michael J Passineau; Fiscal Year: 2013
    ..Our application is designed to improve upon this strategy by utilizing a novel ultrasound-assisted gene transfer method to deliver the Aquaporin-1 gene drug, thereby obviating the toxicity of viral vectors. ..
  52. Kidney-targeted gene delivery for cystinosis
    Stephanie Cherqui; Fiscal Year: 2012
    ..It also represents a proof of concept for a kidney-specific therapy for other hereditary nephropathies. ..
  53. Identifying and testing new targets for Parkinson Disease gene therapy
    Nicholas Muzyczka; Fiscal Year: 2013
    ....
  54. Altering Energy Balance by Systemic Delivery of RNAi to the Neuroendocrine Brain
    Sergio R Ojeda; Fiscal Year: 2013
    ..We also anticipate that these studies will provide the basis for new delivery strategies to the brain for basic research purposes and emerging therapies. ..
  55. Self-complementary rAAV9 Systemic Gene Delivery Treatment for MPS Type IIIA
    Douglas M McCarty; Fiscal Year: 2013
    ..Successful completion of the project is expected to have an immediate impact on the MPS IIIA patient population, with a working therapeutic procedure in hand to advance to the clinical testing process. ..
  56. XIAP Gene Therapy in Huntington's Disease
    Michael G Kaplitt; Fiscal Year: 2013
    ..Given our promising preliminary data and recent use of gene therapy in human Parkinson's disease, this application may also facilitate development of XIAP gene therapy for human HD. ..
  57. MicroRNA to decrease vascular CaV1.2 in hypertension
    Philip T Palade; Fiscal Year: 2013
    ..A longer lasting therapy with fewer side effects may be extremely beneficial for the >40 million Americans whose hypertension is not properly managed. ..
  58. rAAV-GDNF to study mesolimbic control of body mass
    Ronald J Mandel; Fiscal Year: 2012
    ..A series of experiments are proposed to look at which anatomical structures contribute to this important novel effect and to determine if dopamine is required to observe GDNF-induced weight loss. ..
  59. Achromatopsia - Disease Mechanisms and Cone-Directed Gene Therapy
    Andras Komaromy; Fiscal Year: 2013
    ..This research proposal focuses on the development of a new gene therapy to recover diseased cones and their function and to restore day-vision ..
  60. Muscle-Resident Stem Cells for Angiogenesis and Vascular Maturation in PAD
    Christopher D Kontos; Fiscal Year: 2013
    ..Furthermore, these studies may lead to effective therapies for the treatment of PAD. ..
  61. Neural Plasticity During Acclimatization to Hypoxia
    Frank L Powell; Fiscal Year: 2013
    ....
  62. Tailoring AAV Vectors for Glioma Immunotherapy
    Ou Cao; Fiscal Year: 2011
    ....
  63. WEILL CORNELL PROGRAM OF EXCELLENCE IN GENE THERAPY
    Ronald Crystal; Fiscal Year: 2005
    ..End of Abstract) ..
  64. Novel RNAi Inhibits Both Inflammation and Bone Resorption in Oral Diseases
    Yi Ping Li; Fiscal Year: 2010
    ..Such translational application of Atp6i TIRC7 gene silencing strategies would save an enormous amount of money and time spent on repairing the severe gum and bone defects. 1 ..
  65. Transduction of the Mouse Auditory System with AAV
    DIANA LURIE; Fiscal Year: 2003
    ..The focus of these future studies will be on delivering specific genes to the auditory system that potentially play a role in both the functional recovery of the cochlea, as well as neuroprotection following cochlear damage. ..
  66. Gene Therapy for hemophilia using muscle-expressed FVIIa
    Katherine A High; Fiscal Year: 2011
    ..The proposed work will allow us to increase the therapeutic applicability of our approach and enhance its safety, prior to a clinical application. ..
  67. Dystrophin restoration in two animal models of Duchenne Muscular Dystrophy
    LOUISE RODINO; Fiscal Year: 2009
    ..Finally, the optimal AAV serotype carrying micro-dystrophin in the mouse will be perfused into the femoral artery of the golden retriever muscular dystrophy (GRMD) dog (Aim 3). ..
  68. PARVOVIRUS VECTORS FOR HUMAN GENE THERAPY
    Arun Srivastava; Fiscal Year: 2002
    ..The knowledge gained from these studies will be applicable in further development of AAV and parvovirus B19 vectors and their optimal use in gene therapy of beta-thalassemia and sickle-cell disease. ..
  69. PARVOVIRUS VECTORS FOR HUMAN GENE THERAPY
    Arun Srivastava; Fiscal Year: 2004
    ..The knowledge gained from these studies will be applicable in further development of AAV and parvovirus B19 vectors and their optimal use in gene therapy of beta-thalassemia and sickle-cell disease. ..
  70. Novel Gene Delivery Development for Spinal Muscular Atrophy
    Brian Kaspar; Fiscal Year: 2009
    ..We have discovered a novel delivery platform for highly efficient targeting of motor neurons in neonatal animals. We will develop these findings for the potential to translate into human SMA clinical trials. ..
  71. Scalable Production of New Generation Adeno-Associated Virus Gene Therapy Vectors
    MARTIN W LOCK; Fiscal Year: 2010
    ..The overall goal of this project is to develop a large-scale production system for the commercial manufacture of a novel therapeutic for familial hypercholesterolemia. ..
  72. Gene Therapy for the Hemophilias
    Christopher Walsh; Fiscal Year: 2006
    ..Each method will be optimized and in AAV vectors for FVIII production and tested in vivo using immunodeficient and FVIII knockout mice and hemophilic A canines. ..
  73. Enhancing Gene Therapy by Designing Chimeric AAV Virions
    JARROD JOHNSON; Fiscal Year: 2009
    ..Through manipulating these components, it will soon be possible to design virions that are specialized for delivering therapeutics to cells affected by many different genetic disorders and diseases. ..