Genomes and Genes
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.
Publications352 found, 100 shown here
- Safety and efficacy of gene transfer for Leber's congenital amaurosisAlbert 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...
- Adenovirus-associated virus vector-mediated gene transfer in hemophilia BAmit 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...
- Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 yearsSamuel 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...
- Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune responseCatherine 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...
- Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapyGuang 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....
- Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injectionCarmela 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...
- 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 trialWilliam 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...
- Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challengesFederico 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...
- Effect of gene therapy on visual function in Leber's congenital amaurosisJames 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].)...
- Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytesKevin 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...
- Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administrationFrancesca 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...
- 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 systemCorinna 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...
- Next generation of adeno-associated virus 2 vectors: point mutations in tyrosines lead to high-efficiency transduction at lower dosesLi 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...
- 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 vectorsSylvie 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...
- The 37/67-kilodalton laminin receptor is a receptor for adeno-associated virus serotypes 8, 2, 3, and 9Bassel 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...
- Intravenous scAAV9 delivery of a codon-optimized SMN1 sequence rescues SMA miceElisa 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...
- A viral assembly factor promotes AAV2 capsid formation in the nucleolusFlorian 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...
- Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMNKevin 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...
- Dystrophin immunity in Duchenne's muscular dystrophyJerry 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.)...
- Comparative cardiac gene delivery of adeno-associated virus serotypes 1-9 reveals that AAV6 mediates the most efficient transduction in mouse heartCarmela 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...
- Robust systemic transduction with AAV9 vectors in mice: efficient global cardiac gene transfer superior to that of AAV8Katsuya 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...
- Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trialMichael 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...
- CERE-110, an adeno-associated virus-based gene delivery vector expressing human nerve growth factor for the treatment of Alzheimer's diseaseRonald 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...
- High-resolution labeling and functional manipulation of specific neuron types in mouse brain by Cre-activated viral gene expressionSandra J Kuhlman
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America
PLoS ONE 3:e2005. 2008....
- Preclinical differences of intravascular AAV9 delivery to neurons and glia: a comparative study of adult mice and nonhuman primatesSteven 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...
- Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 yearArtur 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...
- AAV-mediated hippocampal expression of short and long Homer 1 proteins differentially affect cognition and seizure activity in adult ratsMatthias 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...
- High-efficiency transduction of the mouse retina by tyrosine-mutant AAV serotype vectorsHilda 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...
- Optimizing promoters for recombinant adeno-associated virus-mediated gene expression in the peripheral and central nervous system using self-complementary vectorsSteven J Gray
Gene Therapy Center, University of North Carolina, Chapel Hill, NC 27599, USA
Hum Gene Ther 22:1143-53. 2011....
- The AAV vector toolkit: poised at the clinical crossroadsAravind 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...
- Successful attenuation of humoral immunity to viral capsid and transgenic protein following AAV-mediated gene transfer with a non-depleting CD4 antibody and cyclosporineJ 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...
- Transduction characteristics of adeno-associated virus vectors expressing cap serotypes 7, 8, 9, and Rh10 in the mouse brainCassia 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...
- CD8(+) T-cell responses to adeno-associated virus capsid in humansFederico 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...
- Systemic gene delivery in large species for targeting spinal cord, brain, and peripheral tissues for pediatric disordersAdam 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...
- Engineering of human pluripotent stem cells by AAV-mediated gene targetingIram 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...
- Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS modelBrian 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...
- New recombinant serotypes of AAV vectorsGuangping 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...
- Self-complementary AAV vectors; advances and applicationsDouglas 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...
- Recombinant adeno-associated virus serotype 9 leads to preferential cardiac transduction in vivoChristina 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....
- Real-time single-molecule imaging of the infection pathway of an adeno-associated virusG 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...
- The genome of self-complementary adeno-associated viral vectors increases Toll-like receptor 9-dependent innate immune responses in the liverAshley 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...
- Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesisD 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...
- AAV8, 9, Rh10, Rh43 vector gene transfer in the rat brain: effects of serotype, promoter and purification methodRonald 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...
- Exchange of surface proteins impacts on viral vector cellular specificity and transduction characteristics: the retina as a modelA 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...
- Schwann cell targeting via intrasciatic injection of AAV8 as gene therapy strategy for peripheral nerve regenerationJ 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...
- Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's diseaseVanesa 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...
- Adeno-associated virus serotype 4 (AAV4) and AAV5 both require sialic acid binding for hemagglutination and efficient transduction but differ in sialic acid linkage specificityN 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...
- Adeno-associated virus serotype 6 capsid tyrosine-to-phenylalanine mutations improve gene transfer to skeletal muscleChunping 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...
- Adeno-associated viruses undergo substantial evolution in primates during natural infectionsGuangping 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...
- Long-term retinal function and structure rescue using capsid mutant AAV8 vector in the rd10 mouse, a model of recessive retinitis pigmentosaJi 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...
- Intracellular transport of recombinant adeno-associated virus vectorsM Nonnenmacher
Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY 10029, USA
Gene Ther 19:649-58. 2012....
- 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 brainNikisha 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...
- A simplified baculovirus-AAV expression vector system coupled with one-step affinity purification yields high-titer rAAV stocks from insect cellsRichard 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...
- Epidermal growth factor receptor is a co-receptor for adeno-associated virus serotype 6Melodie 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...
- Characterization of a recombinant adeno-associated virus type 2 Reference Standard MaterialMartin 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...
- Comparison of adeno-associated viral vector serotypes for spinal cord and motor neuron gene deliveryBrooke 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...
- AAV-mediated photoreceptor transduction of the pig cone-enriched retinaC 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...
- Gene targeting in human pluripotent stem cells with adeno-associated virus vectorsKaoru 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...
- Novel adeno-associated virus serotypes efficiently transduce murine photoreceptorsMariacarmela Allocca
Telethon Institute of Genetics and Medicine, Via P Castellino 111, 80131 Napoli, Italy
J Virol 81:11372-80. 2007....
- Novel AAV serotypes for improved ocular gene transferCorinna 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...
- The TLR9-MyD88 pathway is critical for adaptive immune responses to adeno-associated virus gene therapy vectors in miceJiangao Zhu
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
J Clin Invest 119:2388-98. 2009....
- Preferential labeling of inhibitory and excitatory cortical neurons by endogenous tropism of adeno-associated virus and lentivirus vectorsJ 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...
- Production and characterization of adeno-associated viral vectorsJoshua 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...
- Gene therapy restores vision in a canine model of childhood blindnessG 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...
- Expression of shRNA from a tissue-specific pol II promoter is an effective and safe RNAi therapeuticJeffery C Giering
Department of Pediatrics, Stanford University, Stanford, California 94305, USA
Mol Ther 16:1630-6. 2008....
- 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 miceYona 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...
- Induction of functional neovascularization by combined VEGF and angiopoietin-1 gene transfer using AAV vectorsNikola 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...
- Activation of the NF-kappaB pathway by adeno-associated virus (AAV) vectors and its implications in immune response and gene therapyGiridhara 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....
- Adeno-associated virus (AAV) serotype 9 provides global cardiac gene transfer superior to AAV1, AAV6, AAV7, and AAV8 in the mouse and ratLawrence 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...
- Insect cells as a factory to produce adeno-associated virus type 2 vectorsMasashi 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...
- 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 miMarco 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....
- Adeno-associated virus serotype-9 efficiently transduces the retinal outer plexiform layerBo 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...
- Alpha2,3 and alpha2,6 N-linked sialic acids facilitate efficient binding and transduction by adeno-associated virus types 1 and 6Zhijian 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....
- Intrastriatal rAAV-mediated delivery of anti-huntingtin shRNAs induces partial reversal of disease progression in R6/1 Huntington's disease transgenic miceEdgardo 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...
- Enhancement of adeno-associated virus infection by mobilizing capsids into and out of the nucleolusJarrod 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...
- 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 vectorsMei 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...
- Changes in adeno-associated virus-mediated gene delivery in retinal degenerationKathleen 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...
- Cell-type-specific characteristics modulate the transduction efficiency of adeno-associated virus type 2 and restrain infection of endothelial cellsKatri 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...
- H2AX is required for cell cycle arrest via the p53/p21 pathwayMichalis 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...
- Intracellular trafficking of adeno-associated viral vectorsW 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...
- 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 deliveryMichel 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...
- Restoration of cone vision in the CNGA3-/- mouse model of congenital complete lack of cone photoreceptor functionStylianos 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...
- High-efficiency transduction and correction of murine hemophilia B using AAV2 vectors devoid of multiple surface-exposed tyrosinesDavid 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...
- Differential transgene expression in brain cells in vivo and in vitro from AAV-2 vectors with small transcriptional control unitsS 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...
- Production of CFTR-null and CFTR-DeltaF508 heterozygous pigs by adeno-associated virus-mediated gene targeting and somatic cell nuclear transferChristopher 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...
- Worldwide epidemiology of neutralizing antibodies to adeno-associated virusesRoberto 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...
- A single intravenous injection of adeno-associated virus serotype-9 leads to whole body skeletal muscle transduction in dogsYongping 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...
- The mutant human ND4 subunit of complex I induces optic neuropathy in the mouseXiaoping 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...
- Stereotaxic gene delivery in the rodent brainAli 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...
- Long-term inhibition of glycosphingolipid accumulation in Fabry model mice by a single systemic injection of AAV1 vector in the neonatal periodKoichi 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...
- Adeno-associated virus gene repair corrects a mouse model of hereditary tyrosinemia in vivoNICOLE 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...
- Correction of neurological disease of mucopolysaccharidosis IIIB in adult mice by rAAV9 trans-blood-brain barrier gene deliveryHaiyan 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...
- Dimerizer regulation of AADC expression and behavioral response in AAV-transduced 6-OHDA lesioned ratsLaura 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...
- AAV vector-mediated reversal of hypoglycemia in canine and murine glycogen storage disease type IaDwight 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...
- Therapeutic neonatal hepatic gene therapy in mucopolysaccharidosis VII dogsKatherine 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...
- Disease rescue and increased lifespan in a model of cardiomyopathy and muscular dystrophy by combined AAV treatmentsCarmen 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...
- Controlling neuropathic pain by adeno-associated virus driven production of the anti-inflammatory cytokine, interleukin-10Erin 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...
- Versatility of AAV vectors for retinal gene transferEnrico 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...
- Long-term inducible gene expression in the eye via adeno-associated virus gene transfer in nonhuman primatesCorinna 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...
- Differential activation of innate immune responses by adenovirus and adeno-associated virus vectorsAnne Kathrin Zaiss
Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta T2N 4N1, Canada
J Virol 76:4580-90. 2002....
- High-level transgene expression in nonhuman primate liver with novel adeno-associated virus serotypes containing self-complementary genomesGuang 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...
- NIH Director's Pioneer AwardERICH JARVIS; Fiscal Year: 2009..Repairing the pathway in vocal learners, when damaged, would have profound impact for correcting neurological disorders of speech. ..
- Ethanol Regulation of Serum Glucocorticoid Kinase IBLAIR 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. ..
- Gene Therapy with Cardiotropic Vectors for the Treatment of Heart FailureRoger J Hajjar; Fiscal Year: 2013....
- Role of Potent Trophic Factors on Glia and Motor Neurons in ALSBrian 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. ..
- CTL response to AAV VectorRichard J Samulski; Fiscal Year: 2013....
- RNA interference therapy for Huntington's disease: studies in non-human primatesBeverly 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. ..
- Testing the efficacy of PGC-1alpha as a therapeutic target for Parkinson's diseasHANS BUELER; Fiscal Year: 2010..abstract_text> ..
- Leptin function &resistance in midbrain VTA &SN in reward eating &obesityYI 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. ..
- Gene-Engineered and Targeted Stem Cell Therapy for MyelomaSelvarangan Ponnazhagan; Fiscal Year: 2013..Successful completion of these studies will allow us to initiate phase-1 human clinical trials. ..
- Gene Therapy for Retinitis PigmentosaRajendra Kumar-Singh; Fiscal Year: 2012..that are collectively the most common causes of blindness in the United States. ..
- Modeling schizophrenia gamma deficits using cell-specific RNAi knockdown of GAD67RITCHIE EDWARD BROWN; Fiscal Year: 2012....
- Novel therapy for monoamine neurotransmitter deficiency in PKUCary 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. ..
- MECHANISMS OF MALADAPTATION IN HEART FAILUREHoward A Rockman; Fiscal Year: 2013..Furthermore, the proposed studies will lead to new targets to treat cardiac hypertrophy and heart failure in humans. ..
- Regulated Transgene Expression in the RetinaJames M Wilson; Fiscal Year: 2010....
- Role of Stasimon Dysfunction in Spinal Muscular AtrophyLivio 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. ..
- Effects of ozone exposure on expression and function of surfactant protein DAngela 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. ..
- Gene therapy in the corneaRAJIV 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. ..
- Control of Breathing and Pompe DiseaseDavid D Fuller; Fiscal Year: 2013..This renewal application targets optimization of adeno-associated virus (AAV) based therapies to treat respiratory neurons in Pompe disease. ..
- c-Myc transcription in intestinal growth, differentiation, and carcinogenesisGregory 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. ..
- Inflammation and Oxidative Stress in Parkinsons DiseasePaula C Bickford; Fiscal Year: 2013..If these therapies have significant clinical potential this will be a step forward for Parkinsons therapeutics. ..
- Role of complement in alpha-synuclein based models of Parkinson diseaseHEATHER 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. ..
- AAV vectors for retinal delivery in a mouse model of age-related retinopathyKATHARINE 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. ..
- TBI epileptogenesis: pathologic hippocampal L-glut synaptic plasticityJohn T Slevin; Fiscal Year: 2011....
- Dual AAV Vectors for Duchenne Muscular Dystrophy TherapyDongsheng Duan; Fiscal Year: 2012..Our findings will pave the way to eventually move dual AAV gene therapy to human trials in the future. ..
- Viral Gene Expression to Therapeutic Levels in Models of Heart FailureJoseph 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. ..
- Towards a Model of Fanconi AnemiaBEVERLY 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. ..
- Novel Protective Antiapoptotic Action of Alpha 1-Antitrypsin In EmphysemaRubin M Tuder; Fiscal Year: 2011..abstract_text> ..
- Neuroprotective role of RAB3B in rodent models of Parkinson's diseaseChee 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. ..
- Neuron-specific block of T-type calcium channelsEdward 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. ..
- Novel Adeno-Associated Viral Therapy for Wet Age-Related Macular DegenerationJames M Wilson; Fiscal Year: 2012....
- Diabetes Erectile dysfunction and apoptosis of cavernous tissuesRajvir 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. ..
- Defining a clinically relevant time point for astrocyte targeted therapy in ALSBrian 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. ..
- Phase 2 Study of rAAV1-CB-hAAT for Treatment of Alpha-1 Antitrypsin DeficiencyJeffrey 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. ..
- Novel Adeno-Associated Viral Therapy for X-linked Retinitis PigmentosaJames 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. ..
- FAH-Deficient PigsScott L Nyberg; Fiscal Year: 2011..Thus the demand for these new pigs is worthy of commercialization. ..
- Glioma immunotherapy with strategies based on autonomous parvovirus MVMpJUSTIN 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. ..
- Development of a human Oct-4 gene-targeted reporter cell lineGREGORY LENO; Fiscal Year: 2010..Efficiently reprogrammed human cells have viable commercial applications in regenerative medicine. ..
- Translating CNS therapies for the NCLs from rodent models to humansBeverly L Davidson; Fiscal Year: 2010....
- Gene enhanced cartilage repair in a cytokine permissive environmentAlan 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. ..
- Role of Calcium-Activated Chloride Channels in Airway Disease PhenotypesANAND 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. ..
- Molecular Evolution Strategies to Derive New Recombinant AAV VectorsMark A Kay; Fiscal Year: 2012..Once the new AAV vectors are created, they will be tested in animal models of human disease. ..
- Novel Vaginal Microbicides Based On Stable AAV-Neutralizing Antibody Gene TransfeWayne A Marasco; Fiscal Year: 2010..A protective genetic microbicide delivered to the female lower genital track could dramatically slow the spread of HIV/AIDS. ..
- 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. ..
- Screens for host DNA replication and repair factors involved in viral infectionMatthew 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. ..
- VGF function in depression and antidepressant treatmentStephen R Salton; Fiscal Year: 2013....
- Modification of AdenoAssociated Virus to deliver DNA directly to MitochondriaJohn Guy; Fiscal Year: 2011..We will share the vector with other groups whose goal it is to treat these disorders. ..
- Histone Deacetylases: Regulators of Cocaine Reward and Targets for TherapeuticsMARCELO 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. ..
- PTEN Gene Therapy for Vein Graft DiseaseChristopher 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. ..
- Investigating the RhoA/ROCK pathway for the treatment of Alzheimer's diseaseJEREMY HARTFORD HERSKOWITZ; Fiscal Year: 2013....
- Exosome based therapeutics in Huntington's diseaseNeil 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. ..
- Ultrasound-Assisted AQP1 Gene Therapy for Functional Restoration of Salivary GlanMichael 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. ..
- Kidney-targeted gene delivery for cystinosisStephanie Cherqui; Fiscal Year: 2012..It also represents a proof of concept for a kidney-specific therapy for other hereditary nephropathies. ..
- Identifying and testing new targets for Parkinson Disease gene therapyNicholas Muzyczka; Fiscal Year: 2013....
- Altering Energy Balance by Systemic Delivery of RNAi to the Neuroendocrine BrainSergio 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. ..
- Self-complementary rAAV9 Systemic Gene Delivery Treatment for MPS Type IIIADouglas 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. ..
- XIAP Gene Therapy in Huntington's DiseaseMichael 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. ..
- MicroRNA to decrease vascular CaV1.2 in hypertensionPhilip 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. ..
- rAAV-GDNF to study mesolimbic control of body massRonald 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. ..
- Achromatopsia - Disease Mechanisms and Cone-Directed Gene TherapyAndras 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 ..
- Muscle-Resident Stem Cells for Angiogenesis and Vascular Maturation in PADChristopher D Kontos; Fiscal Year: 2013..Furthermore, these studies may lead to effective therapies for the treatment of PAD. ..
- Neural Plasticity During Acclimatization to HypoxiaFrank L Powell; Fiscal Year: 2013....
- Tailoring AAV Vectors for Glioma ImmunotherapyOu Cao; Fiscal Year: 2011....
- WEILL CORNELL PROGRAM OF EXCELLENCE IN GENE THERAPYRonald Crystal; Fiscal Year: 2005..End of Abstract) ..
- Novel RNAi Inhibits Both Inflammation and Bone Resorption in Oral DiseasesYi 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 ..
- Transduction of the Mouse Auditory System with AAVDIANA 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. ..
- Gene Therapy for hemophilia using muscle-expressed FVIIaKatherine 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. ..
- Dystrophin restoration in two animal models of Duchenne Muscular DystrophyLOUISE 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). ..
- PARVOVIRUS VECTORS FOR HUMAN GENE THERAPYArun 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. ..
- PARVOVIRUS VECTORS FOR HUMAN GENE THERAPYArun 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. ..
- Novel Gene Delivery Development for Spinal Muscular AtrophyBrian 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. ..
- Scalable Production of New Generation Adeno-Associated Virus Gene Therapy VectorsMARTIN 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. ..
- Gene Therapy for the HemophiliasChristopher 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. ..
- Enhancing Gene Therapy by Designing Chimeric AAV VirionsJARROD 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. ..