gene therapy


Summary: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia.

Top Publications

  1. pmc The ERBB3 receptor in cancer and cancer gene therapy
    G Sithanandam
    SAIC Frederick, MD 21702, USA
    Cancer Gene Ther 15:413-48. 2008
  2. ncbi Results from a phase I safety trial of hAADC gene therapy for Parkinson disease
    J L Eberling
    Department of Molecular Imaging and Neuroscience, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
    Neurology 70:1980-3. 2008
  3. 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
  4. pmc A third-generation lentivirus vector with a conditional packaging system
    T Dull
    Cell Genesys, Foster City, California 94404, USA
    J Virol 72:8463-71. 1998
  5. ncbi LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1
    S Hacein-Bey-Abina
    INSERM Unit 429, Cedex 15, France
    Science 302:415-9. 2003
  6. ncbi Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy
    Nathalie Cartier
    INSERM UMR745, University Paris Descartes, 75279 Paris, France
    Science 326:818-23. 2009
  7. pmc Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1
    Salima Hacein-Bey-Abina
    Department of Biotherapy, Hopital Necker Enfants Malades, Assistance Publique Hopitaux de Paris AP HP, Universite Rene Descartes, Paris, France
    J Clin Invest 118:3132-42. 2008
  8. pmc Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia
    Marina Cavazzana-Calvo
    Clinical Investigation Center in Biotherapy, Groupe Hospitalier Universitaire Ouest, Inserm Assistance Publique Hôpitaux de Paris, Paris 75015, France
    Nature 467:318-22. 2010
  9. 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
  10. 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

Detail Information

Publications293 found, 100 shown here

  1. pmc The ERBB3 receptor in cancer and cancer gene therapy
    G Sithanandam
    SAIC Frederick, MD 21702, USA
    Cancer Gene Ther 15:413-48. 2008
    ..Several approaches for targeting ERBB3 in cancers have been tested or proposed. Small inhibitory RNA (siRNA) to ERBB3 or AKT is showing promise as a therapeutic approach to treatment of lung adenocarcinoma...
  2. ncbi Results from a phase I safety trial of hAADC gene therapy for Parkinson disease
    J L Eberling
    Department of Molecular Imaging and Neuroscience, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
    Neurology 70:1980-3. 2008
    ..These studies led to the initiation of a phase I safety trial. Here we report the findings for the first cohort of five patients...
  3. 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.
  4. pmc A third-generation lentivirus vector with a conditional packaging system
    T Dull
    Cell Genesys, Foster City, California 94404, USA
    J Virol 72:8463-71. 1998
    ..While the actual biosafety of the vector will ultimately be proven in vivo, the improved design presented here should facilitate testing of lentivirus vectors...
  5. ncbi LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1
    S Hacein-Bey-Abina
    INSERM Unit 429, Cedex 15, France
    Science 302:415-9. 2003
    ..However, almost 3 years after gene therapy, uncontrolled exponential clonal proliferation of mature T cells (with gammadelta+ or alphabeta+ T cell ..
  6. ncbi Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy
    Nathalie Cartier
    INSERM UMR745, University Paris Descartes, 75279 Paris, France
    Science 326:818-23. 2009
    ..ALD progression can be halted by allogeneic hematopoietic cell transplantation (HCT). We initiated a gene therapy trial in two ALD patients for whom there were no matched donors...
  7. pmc Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1
    Salima Hacein-Bey-Abina
    Department of Biotherapy, Hopital Necker Enfants Malades, Assistance Publique Hopitaux de Paris AP HP, Universite Rene Descartes, Paris, France
    J Clin Invest 118:3132-42. 2008
    Previously, several individuals with X-linked SCID (SCID-X1) were treated by gene therapy to restore the missing IL-2 receptor gamma (IL2RG) gene to CD34+ BM precursor cells using gammaretroviral vectors...
  8. pmc Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia
    Marina Cavazzana-Calvo
    Clinical Investigation Center in Biotherapy, Groupe Hospitalier Universitaire Ouest, Inserm Assistance Publique Hôpitaux de Paris, Paris 75015, France
    Nature 467:318-22. 2010
    The β-haemoglobinopathies are the most prevalent inherited disorders worldwide. Gene therapy of β-thalassaemia is particularly challenging given the requirement for massive haemoglobin production in a lineage-specific manner and the ..
  9. 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...
  10. 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.
  11. 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.
  12. ncbi Restoration of anti-Aspergillus defense by neutrophil extracellular traps in human chronic granulomatous disease after gene therapy is calprotectin-dependent
    Matteo Bianchi
    Division of Immunology Hematology BMT, University Children s Hospital Zurich, Zurich, Switzerland
    J Allergy Clin Immunol 127:1243-52.e7. 2011
    ..This process is defective in chronic granulomatous disease (CGD) because of impaired phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase function...
  13. 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
    ..Vectors based on these novel, nonhuman primate AAVs should be considered for human gene therapy because of low reactivity to antibodies directed to human AAVs and because gene transfer efficiency in muscle ..
  14. ncbi Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease
    Stefan Stein
    Institute for Biomedical Research, Georg Speyer Haus, Frankfurt, Germany
    Nat Med 16:198-204. 2010
    ..Here we report on the molecular and cellular events observed in two young adults with X-CGD treated by gene therapy in 2004...
  15. pmc Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen
    Laura A Johnson
    Surgery Branch, Hatfield Clinical Research Center, National Cancer Institute NIH, Bethesda, MD 20892, USA
    Blood 114:535-46. 2009
    b>Gene therapy of human cancer using genetically engineered lymphocytes is dependent on the identification of highly reactive T-cell receptors (TCRs) with antitumor activity...
  16. 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...
  17. 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.
  18. ncbi Design and development of polymers for gene delivery
    Daniel W Pack
    Department of Chemical and Biomolecular Engineering, University of Illinois, Box C 3, 600 South Mathews Avenue, Urbana, IL 61801, USA
    Nat Rev Drug Discov 4:581-93. 2005
    The lack of safe and efficient gene-delivery methods is a limiting obstacle to human gene therapy. Synthetic gene-delivery agents, although safer than recombinant viruses, generally do not possess the required efficacy...
  19. ncbi Progress and problems with the use of viral vectors for gene therapy
    Clare E Thomas
    Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA
    Nat Rev Genet 4:346-58. 2003
    b>Gene therapy has a history of controversy. Encouraging results are starting to emerge from the clinic, but questions are still being asked about the safety of this new molecular medicine...
  20. ncbi Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial
    Albert M Maguire
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Lancet 374:1597-605. 2009
    b>Gene therapy has the potential to reverse disease or prevent further deterioration of vision in patients with incurable inherited retinal degeneration...
  21. 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 and efficacy of gene therapy for inherited retinal diseases is being tested in humans affected with Leber's congenital amaurosis (LCA), an autosomal recessive blinding disease...
  22. ncbi Gene therapy for immunodeficiency due to adenosine deaminase deficiency
    Alessandro Aiuti
    San Raffaele Telethon Institute for Gene Therapy, Milan, Italy
    N Engl J Med 360:447-58. 2009
    We investigated the long-term outcome of gene therapy for severe combined immunodeficiency (SCID) due to the lack of adenosine deaminase (ADA), a fatal disorder of purine metabolism and immunodeficiency.
  23. 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. ( number, NCT00643747 [].)...
  24. pmc Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector
    Dawn E Bowles
    Department of Surgery, Division of Surgical Sciences, Duke University Medical Center, Durham, North Carolina, USA
    Mol Ther 20:443-55. 2012
    ..g., limb infusion gene delivery) and should usher in the next generation of viral delivery systems for human gene transfer...
  25. ncbi Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer
    Steven E Raper
    Department of Surgery, University of Pennsylvania School of Medicine, BRB II III Rm, 607 421 Curie Blvd, Philadelphia, PA 19104, USA
    Mol Genet Metab 80:148-58. 2003
    ..male with partial ornithine transcarbamylase (OTC) deficiency who participated in a pilot (safety) study of gene therapy. The vector used for this trial was based on human adenovirus type 5, deleted in E1 and E4, and contained human ..
  26. 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
    The adeno-associated virus (AAV) is one of the most promising viral vectors for human gene therapy. As with any potential therapeutic system, a thorough understanding of it at the in vitro and in vivo levels is required...
  27. ncbi Zinc-finger nucleases: the next generation emerges
    Toni Cathomen
    Institute of Virology CBF, Charite Medical School, Berlin, Germany
    Mol Ther 16:1200-7. 2008
    Methods of modifying the human genome precisely and efficiently hold great promise for revolutionizing the gene therapy arena...
  28. pmc Progress and prospects: zinc-finger nucleases as gene therapy agents
    D Carroll
    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112 5650, USA
    Gene Ther 15:1463-8. 2008
    ..A number of recent papers have shown how this technology can be applied effectively to models of human gene therapy. Significant target genes and useful methods of ZFN delivery have been reported...
  29. 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...
  30. ncbi Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure
    Mariell Jessup
    Heart Failure Transplant Program, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA
    Circulation 124:304-13. 2011
    ..Adeno-associated virus type 1/sarcoplasmic reticulum Ca(2+)-ATPase was assessed in a randomized, double-blind, placebo-controlled, phase 2 study in patients with advanced heart failure...
  31. 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
    ..2%). Vectors based on AAV5, AAV8, and AAV9 may have an advantage for gene therapy in humans...
  32. ncbi AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial
    Peter A LeWitt
    Wayne State University School of Medicine, Parkinson s Disease and Movement Disorders Program, Henry Ford West Bloomfield Hospital, MI, USA
    Lancet Neurol 10:309-19. 2011
    ..We aimed to assess the effect of bilateral delivery of AAV2-GAD in the subthalamic nucleus compared with sham surgery in patients with advanced Parkinson's disease...
  33. pmc Cancer regression in patients after transfer of genetically engineered lymphocytes
    Richard A Morgan
    Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
    Science 314:126-9. 2006
    ..This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer...
  34. ncbi Highly efficient endogenous human gene correction using designed zinc-finger nucleases
    Fyodor D Urnov
    Sangamo BioSciences, Inc, Pt Richmond Tech Center 501, Canal Blvd, Suite A100 Richmond, California 94804, USA
    Nature 435:646-51. 2005
    ..recombination in human cells, a fact that hampers biomedical research and progress towards safe and effective gene therapy. Here we report a general solution using two fundamental biological processes: DNA recognition by C2H2 zinc-..
  35. pmc The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapy
    Eugenio Montini
    San Raffaele Telethon Institute for Gene Therapy, Via Olgettina 58, 20132 Milan, Italy
    J Clin Invest 119:964-75. 2009
    gamma-Retroviral vectors (gammaRVs), which are commonly used in gene therapy, can trigger oncogenesis by insertional mutagenesis...
  36. pmc Restoration of NET formation by gene therapy in CGD controls aspergillosis
    Matteo Bianchi
    Division of Immunology Haematology BMT, University Children s Hospital Zurich, Zurich, Switzerland
    Blood 114:2619-22. 2009
    ..The aim of this study was to determine whether gene therapy restores NET formation in CGD by complementation of NADPH oxidase function, and whether NETs have antimicrobial ..
  37. pmc Clades of Adeno-associated viruses are widely disseminated in human tissues
    Guangping Gao
    Gene Therapy Program, Division of Medical Genetics, Department of Medicine, University of Pennsylvania School of Medicine, 3601 Spruce Street, Philadelphia, PA 19104, USA
    J Virol 78:6381-8. 2004
    The potential for using Adeno-associated virus (AAV) as a vector for human gene therapy has stimulated interest in the Dependovirus genus...
  38. pmc Stem-cell gene therapy for the Wiskott-Aldrich syndrome
    Kaan Boztug
    Department of Pediatric Hematology Oncology, Hannover Medical School, Hannover, Germany
    N Engl J Med 363:1918-27. 2010
    ..We found sustained expression of WAS protein expression in HSC, lymphoid and myeloid cells, and platelets after gene therapy. T and B cells, natural killer (NK) cells, and monocytes were functionally corrected...
  39. pmc Gene therapy in the cornea: 2005--present
    Rajiv R Mohan
    Harry S Truman Memorial Veterans Hospital, 800 Hospital Drive, Columbia, MO 65201, USA
    Prog Retin Eye Res 31:43-64. 2012
    Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders...
  40. pmc Transgenesis by lentiviral vectors: lack of gene silencing in mammalian embryonic stem cells and preimplantation embryos
    Alexander Pfeifer
    The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 99:2140-5. 2002
    ..Ability to transfer foreign genes into human ES cells has potential relevance for the development of gene and cell-based therapies...
  41. ncbi Production and purification of serotype 1, 2, and 5 recombinant adeno-associated viral vectors
    Sergei Zolotukhin
    Powell Gene Therapy Center, 1600 SW Archer Road, College of Medicine, University of Florida, 32610 0266, Gainesville, FL 32610 0266, USA
    Methods 28:158-67. 2002
    ..The purified vector stocks are 99% pure with titers of 1 x 10(12) to 1 x 10(13)vector genomes/ml...
  42. pmc Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa
    William A Beltran
    Section of Ophthalmology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 109:2132-7. 2012
    ..b>Gene therapy in mouse and dog models of a primary retinal pigment epithelium disease has already been translated to human ..
  43. pmc Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells
    Ronald T Mitsuyasu
    Center for Clinical AIDS Research and Education, University of California Los Angeles, 9911 West Pico Boulevard, Suite 980, Los Angeles, California 90035, USA
    Nat Med 15:285-92. 2009
    ..This study indicates that cell-delivered gene transfer is safe and biologically active in individuals with HIV and can be developed as a conventional therapeutic product...
  44. pmc Gene therapy using adeno-associated virus vectors
    Shyam Daya
    Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida 32610 3610, USA
    Clin Microbiol Rev 21:583-93. 2008
    ..In addition, several novel approaches and recent findings that promise to expand AAV's utility are discussed, especially in the context of combining gene therapy ex vivo with new advances in stem or progenitor cell biology.
  45. ncbi Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene
    Luis G Melo
    Department of Medicine, Brigham and Women s Hospital, and Harvard Medical School, Boston, Massachusetts, USA
    Circulation 105:602-7. 2002
  46. ncbi Glucagon-like peptide-1 gene therapy in obese diabetic mice results in long-term cure of diabetes by improving insulin sensitivity and reducing hepatic gluconeogenesis
    Young Sun Lee
    Rosalind Franklin Comprehensive Diabetes Center, Department of Pathology, Chicago Medical School, North Chicago, IL 60064, USA
    Diabetes 56:1671-9. 2007
    ..We hypothesized that continuous production of therapeutic levels of GLP-1 in vivo by a gene therapy strategy may remit hyperglycemia and maintain prolonged normoglycemia...
  47. 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
    Human gene therapy with rAAV2-vector was performed for the RPE65 form of childhood blindness called Leber congenital amaurosis...
  48. ncbi Effective gene therapy with nonintegrating lentiviral vectors
    Rafael J Yáñez-Muñoz
    Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
    Nat Med 12:348-53. 2006
    ..For therapeutic application to postmitotic tissues, this system substantially reduces the risk of insertional mutagenesis...
  49. ncbi Effects of antioxidant gene therapy on retinal neurons and oxidative stress in a model of retinal ischemia/reperfusion
    Yu Liu
    Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, People s Republic of China
    Free Radic Biol Med 52:909-15. 2012
    ..Delivery of the antioxidant gene inhibited I/R-induced RGC and IPL damage by reducing oxidative stress and nitrative stress, suggesting that MnSOD may be relevant for the neuroprotection of the inner retina from I/R-related diseases...
  50. pmc Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma
    Adil I Daud
    Cutaneous Oncology and Experimental Therapeutics Programs, H Lee Moffitt Cancer Center, University of South Florida, Tampa, FL, USA
    J Clin Oncol 26:5896-903. 2008
    ..In vivo electroporation, in preclinical models, significantly enhances gene transfer efficiency while retaining the safety advantages of plasmid DNA...
  51. pmc Efficacy of gene therapy for X-linked severe combined immunodeficiency
    Salima Hacein-Bey-Abina
    Department of Biotherapy, Necker Enfants Malades Hospital, Paris, France
    N Engl J Med 363:355-64. 2010
    The outcomes of gene therapy to correct congenital immunodeficiencies are unknown...
  52. pmc SERCA2a gene therapy restores microRNA-1 expression in heart failure via an Akt/FoxO3A-dependent pathway
    Regalla Kumarswamy
    Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Carl Neuberg Str 1, 30625 Hannover, Germany
    Eur Heart J 33:1067-75. 2012
    ..sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) activity is a hallmark of failing hearts, and SERCA2a gene therapy improves cardiac function in animals and patients with heart failure (HF)...
  53. 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
    ..b>Gene therapy treatment of several mouse and canine models with novel AAV vectors achieved long term phenotypic corrections...
  54. pmc Restoration of hearing in the VGLUT3 knockout mouse using virally mediated gene therapy
    Omar Akil
    Department of Otolaryngology, Head and Neck Surgery, University of California San Francisco, San Francisco, CA 94143, USA
    Neuron 75:283-93. 2012
    ..These findings represent a successful restoration of hearing by gene replacement in mice, which is a significant advance toward gene therapy of human deafness.
  55. ncbi The mitotic clock in skeletal muscle regeneration, disease and cell mediated gene therapy
    V Mouly
    CNRS UMR 7000 faculté de Médecine Pitié Salpétrière, Cytosquelette et Développement, 105 bd de l Hopital, 75634 Paris Cedex 13, France
    Acta Physiol Scand 184:3-15. 2005
    ..This is the case of Oculo-Pharyngeal Muscular Dystrophy (OPMD), a late onset muscular dystrophy, and we participate to a clinical trial using autologous satellite cells isolated from muscles spared by the disease...
  56. ncbi Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury: evidence that angiogenesis participates in alveolarization
    Bernard Thebaud
    Division of Neonatology, Department of Pediatrics, University of Alberta, Edmonton, Canada
    Circulation 112:2477-86. 2005
    ..Vascular endothelial growth factor (VEGF) is a trophic factor required for endothelial cell survival and is abundantly expressed in the lung...
  57. pmc Meganucleases and other tools for targeted genome engineering: perspectives and challenges for gene therapy
    George Silva
    Cellectis Genome Surgery, 102 Avenue Gaston Roussel, Romainville Cedex, France
    Curr Gene Ther 11:11-27. 2011
    The importance of safer approaches for gene therapy has been underscored by a series of severe adverse events (SAEs) observed in patients involved in clinical trials for Severe Combined Immune Deficiency Disease (SCID) and Chromic ..
  58. ncbi Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs
    Maurilio Sampaolesi
    San Raffaele Scientific Institute, Universita Vita e Salute, Stem Cell Research Institute, Via Olgettina 58, 20132 Milan, Italy
    Nature 444:574-9. 2006
    ..The outcome is a remarkable clinical amelioration and preservation of active motility. These data qualify mesoangioblasts as candidates for future stem cell therapy for Duchenne patients...
  59. 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; number, NCT00428935.)...
  60. pmc MECP2 isoform-specific vectors with regulated expression for Rett syndrome gene therapy
    Mojgan Rastegar
    Developmental and Stem Cell Biology Program, SickKids Hospital, Toronto, Ontario, Canada
    PLoS ONE 4:e6810. 2009
    ..Our objective is to develop viral vectors for MECP2 gene transfer into Neural Stem Cells (NSC) and neurons suitable for gene therapy of Rett Syndrome.
  61. ncbi Mesenchymal progenitor cells as cellular vehicles for delivery of oncolytic adenoviruses
    Svetlana Komarova
    Division of Human Gene Therapy, Department of Medicine, Gene Therapy Center, University of Alabama at Birmingham, 901 19th Street South, BMR2 572, Birmingham, AL 35294 3300, USA
    Mol Cancer Ther 5:755-66. 2006
    ..These data show that MPCs can serve as intermediate carriers for replicative adenoviruses and suggest that the natural homing properties of specific cell types can be used for targeted delivery of these virions...
  62. pmc Gene therapy using genetically modified lymphocytes targeting VEGFR-2 inhibits the growth of vascularized syngenic tumors in mice
    Dhanalakshmi Chinnasamy
    Surgery Branch, National Cancer Institute, Clinical Research Center, Bethesda, Maryland 20892, USA
    J Clin Invest 120:3953-68. 2010
    ..T cells transduced with VEGFR-2 CAR showed durable and increased tumor infiltration, correlating with their antitumor effect. This approach provides a potential method for the gene therapy of a variety of human cancers.
  63. ncbi Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease
    J H Kordower
    Department of Neurological Sciences, Rush Presbyterian St Luke s Medical Center, Chicago, IL 60612, USA
    Science 290:767-73. 2000
    ..These data indicate that GDNF delivery using a lentiviral vector system can prevent nigrostriatal degeneration and induce regeneration in primate models of PD and might be a viable therapeutic strategy for PD patients...
  64. ncbi Stem and progenitor cell-mediated tumor selective gene therapy
    K S Aboody
    Division of Hematology Hematopoietic Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA, USA
    Gene Ther 15:739-52. 2008
  65. pmc Worsening of cardiomyopathy using deflazacort in an animal model rescued by gene therapy
    Ida Luisa Rotundo
    Telethon Institute of Genetics and Medicine, Napoli, Italy
    PLoS ONE 6:e24729. 2011
    We have previously demonstrated that gene therapy can rescue the phenotype and extend lifespan in the delta-sarcoglycan deficient cardiomyopathic hamster...
  66. pmc Toward brain tumor gene therapy using multipotent mesenchymal stromal cell vectors
    Daniel Bexell
    Lund Stem Cell Center, Lund University, Lund, Sweden
    Mol Ther 18:1067-75. 2010
    b>Gene therapy of solid cancers has been severely restricted by the limited distribution of vectors within tumors. However, cellular vectors have emerged as an effective migratory system for gene delivery to invasive cancers...
  67. pmc A phase I study of aromatic L-amino acid decarboxylase gene therapy for Parkinson's disease
    Shin Ichi Muramatsu
    Division of Neurology, Department of Medicine, Jichi Medical University, Tochigi, Japan
    Mol Ther 18:1731-5. 2010
    ..Our findings provide class IV evidence regarding the safety and efficacy of AADC gene therapy and warrant further evaluation in a randomized, controlled, phase 2 setting.
  68. pmc Five siRNAs targeting three SNPs may provide therapy for three-quarters of Huntington's disease patients
    Edith L Pfister
    Department of Medicine, Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Curr Biol 19:774-8. 2009
    ..We have designed and validated selective siRNAs for the three SNP sites, laying the foundation for allele-specific RNA interference (RNAi) therapy for HD...
  69. ncbi Clinico-pathological rescue of a model mouse of Huntington's disease by siRNA
    Yu Lai Wang
    Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry NCNP, Tokyo 187 8502, Japan
    Neurosci Res 53:241-9. 2005
    ..Treatments using this siRNA significantly prolonged model mice longevity, improved motor function and slowed down the loss of body weight. This work suggests that siRNA-based therapy is promising as a future treatment for HD...
  70. ncbi Progress in developing cationic vectors for non-viral systemic gene therapy against cancer
    Marie Morille
    Inserm U646, Ingenierie de la Vectorisation Particulaire, Universite d Angers, 10, rue André Boquel, 49100 Angers, France
    Biomaterials 29:3477-96. 2008
    Initially, gene therapy was viewed as an approach for treating hereditary diseases, but its potential role in the treatment of acquired diseases such as cancer is now widely recognized...
  71. ncbi Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy
    D Baksh
    Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892 8022, USA
    J Cell Mol Med 8:301-16. 2004
    ..Current research efforts focused on elucidating the mechanisms regulating MSC differentiation should facilitate the design of optimal in vitro culture conditions to enhance their clinical utility cell and gene therapy.
  72. pmc Hematopoietic-stem-cell-based gene therapy for HIV disease
    Hans Peter Kiem
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Cell Stem Cell 10:137-47. 2012
    ..Here, we review this and other strategies for HSC-based gene therapy for HIV disease.
  73. pmc In vitro and in vivo gene therapy vector evolution via multispecies interbreeding and retargeting of adeno-associated viruses
    Dirk Grimm
    Department of Pediatrics, School of Medicine, Stanford University, Stanford, CA 94305, USA
    J Virol 82:5887-911. 2008
    ..broadly in transduction efficacies and tissue tropisms and thus hold enormous potential as vectors for human gene therapy. In reality, however, their use in patients is restricted by prevalent anti-AAV immunity or by their inadequate ..
  74. ncbi Delivering the goods: viral and non-viral gene therapy systems and the inherent limits on cargo DNA and internal sequences
    Helen Atkinson
    School of Biomedical Sciences, University of Nottingham, Queen s Medical Center, Nottingham NG7 2UH, UK
    Genetica 138:485-98. 2010
    Viruses have long been considered to be the most promising tools for human gene therapy. However, the initial enthusiasm for the use of viruses has been tarnished in the light of potentially fatal side effects...
  75. pmc Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies
    Anneke I den Hollander
    Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
    J Clin Invest 120:3042-53. 2010
  76. 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...
  77. 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 ..
  78. ncbi Emerging potential of transposons for gene therapy and generation of induced pluripotent stem cells
    Thierry VandenDriessche
    Flanders Institute for Biotechnology VIB, Vesalius Research Center, University of Leuven, Leuven, Belgium
    Blood 114:1461-8. 2009
    Effective gene therapy requires robust delivery of the desired genes into the relevant target cells, long-term gene expression, and minimal risks of secondary effects...
  79. ncbi Comprehensive genomic access to vector integration in clinical gene therapy
    Richard Gabriel
    Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany
    Nat Med 15:1431-6. 2009
    Retroviral vectors have induced subtle clonal skewing in many gene therapy patients and severe clonal proliferation and leukemia in some of them, emphasizing the need for comprehensive integration site analyses to assess the biosafety and ..
  80. pmc Allele-specific silencing of dominant disease genes
    Victor M Miller
    Department of Neurology, Graduate Program in Genetics, University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, IA 52242, USA
    Proc Natl Acad Sci U S A 100:7195-200. 2003
    ..These studies establish that siRNA can be engineered to silence disease genes differing by a single nucleotide and highlight a key role for SNPs in extending the utility of siRNA in dominantly inherited disorders...
  81. pmc Effects on proliferation and differentiation of multipotent bone marrow stromal cells engineered to express growth factors for combined cell and gene therapy
    Fernando A Fierro
    Institute for Regenerative Cures, University of California, Davis, California 95817, USA
    Stem Cells 29:1727-37. 2011
  82. ncbi Long-term phenotypic correction in factor IX knockout mice by using ΦC31 integrase-mediated gene therapy
    A Keravala
    Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA
    Gene Ther 18:842-8. 2011
    ..bleeding disorder caused by a deficiency of coagulation factor IX (FIX), is an excellent candidate for gene therapy. However, to date, success in hemophilia gene therapy clinical trials has been limited due to failure to ..
  83. ncbi Gene therapy using TRAIL-secreting human umbilical cord blood-derived mesenchymal stem cells against intracranial glioma
    Seong Muk Kim
    Department of Biomedical Science, College of Medicine, Kangnam St Mary s Hospital, The Catholic University of Korea
    Cancer Res 68:9614-23. 2008
    ..These results suggest that human UCB-MSCs have potential use as effective delivery vehicles for therapeutic genes in the treatment of intracranial glioma...
  84. ncbi Polyethylenimine-based non-viral gene delivery systems
    U Lungwitz
    Department of Pharmacy and Chemistry, Pharmaceutical Technology Unit, University of Regensburg, Regensburg, Germany
    Eur J Pharm Biopharm 60:247-66. 2005
    b>Gene therapy has become a promising strategy for the treatment of many inheritable or acquired diseases that are currently considered incurable...
  85. pmc Long-term preservation of cone photoreceptors and restoration of cone function by gene therapy in the guanylate cyclase-1 knockout (GC1KO) mouse
    Sanford L Boye
    Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
    Invest Ophthalmol Vis Sci 52:7098-108. 2011
    ..Here, the authors compared therapy conferred by the aforementioned vectors to that achieved with the highly efficient capsid tyrosine mutant AAV8(Y733F) and asked whether long-term therapy is achievable in this model...
  86. pmc Foamy virus vector integration sites in normal human cells
    Grant D Trobridge
    Department of Medicine, Division of Hematology, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 103:1498-503. 2006
    ..Transcriptional profiling showed that gene expression had little influence on integration site selection. Our findings suggest that FV vectors may have desirable integration properties for gene therapy applications.
  87. ncbi Sustained reduction of vein graft neointima formation by ex vivo TIMP-3 gene therapy
    Sarah J George
    Bristol Heart Institute, University of Bristol, Bristol, United Kingdom
    Circulation 124:S135-42. 2011
    ..However, it is essential to determine whether this approach will provide longer-term benefits...
  88. ncbi Adipose tissue-derived human mesenchymal stem cells mediated prodrug cancer gene therapy
    Lucia Kucerova
    Laboratory of Molecular Oncology, Cancer Research Institute of Slovak Academy of Sciences, Bratislava, Slovakia
    Cancer Res 67:6304-13. 2007
    ..Taken together, these data characterize MSC derived from adipose tissue as suitable delivery vehicles for prodrug converting gene and show their utility for a personalized cell-based targeted cancer gene therapy.
  89. pmc Lens epithelium-derived growth factor fusion proteins redirect HIV-1 DNA integration
    Andrea L Ferris
    HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA
    Proc Natl Acad Sci U S A 107:3135-40. 2010
    ..The ability to redirect HIV-1 DNA integration may help solve the problems associated with the activation of oncogenes when retroviruses are used in gene therapy.
  90. pmc Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study
    Maria Kinali
    The Dubowitz Neuromuscular Centre, University College London Institute of Child Health London, London, UK
    Lancet Neurol 8:918-28. 2009
  91. ncbi Recent developments in transposon-mediated gene therapy
    Mario Di Matteo
    Free University of Brussels, Division of Gene Therapy and Regenerative Medicine, Laarbeeklaan 103, B 1090 Brussels, Belgium
    Expert Opin Biol Ther 12:841-58. 2012
    ..improvement of gene transfer technologies has broad implications for stem cell biology, gene discovery, and gene therapy. Although viral vectors are efficient gene delivery vehicles, their safety, immunogenicity and manufacturing ..
  92. ncbi VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond
    M Giacca
    Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste, Italy
    Gene Ther 19:622-9. 2012
    ..Here, we critically review the VEGF-based therapies that have already reached clinical experimentation and highlight the pleiotropic activities of VEGF factors that might create new opportunities for therapeutic application...
  93. ncbi Gene therapy-directed osteogenesis: BMP-7-transduced human fibroblasts form bone in vivo
    P H Krebsbach
    Center for Biorestoration of Oral Health, University of Michigan, School of Dentistry, Ann Arbor 48109, USA
    Hum Gene Ther 11:1201-10. 2000
    An ex vivo gene therapy strategy was used to achieve localized skeletal regeneration in vivo...
  94. pmc Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension
    M Sean McMurtry
    The Vascular Biology Group and Pulmonary Hypertension Program, University of Alberta, Edmonton, Alberta, Canada
    J Clin Invest 115:1479-91. 2005
    ..b>Gene therapy with inhalation of an adenovirus carrying a phosphorylation-deficient survivin mutant with dominant-negative ..
  95. pmc Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients
    Steven J Howe
    Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, University College London, London, United Kingdom
    J Clin Invest 118:3143-50. 2008
    X-linked SCID (SCID-X1) is amenable to correction by gene therapy using conventional gammaretroviral vectors...
  96. pmc LEDGF hybrids efficiently retarget lentiviral integration into heterochromatin
    Rik Gijsbers
    Division of Molecular Medicine, Katholieke Universiteit Leuven, Leuven, Belgium
    Mol Ther 18:552-60. 2010
    ..Thus, engineered LEDGF/p75 chimeras provide technology for controlling integration site selection by lentiviral vectors...
  97. ncbi Current status of polymeric gene delivery systems
    Tae Gwan Park
    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305 701, Korea
    Adv Drug Deliv Rev 58:467-86. 2006
    b>Gene therapy provides great opportunities for treating diseases from genetic disorders, infections and cancer. To achieve successful gene therapy, development of proper gene delivery systems could be one of the most important factors...
  98. pmc Current advances in retroviral gene therapy
    Youngsuk Yi
    TissueGene, Inc, Rockville, MD 20850, USA
    Curr Gene Ther 11:218-28. 2011
    ..changes since the incidents of leukemia development in X-SCID patients after the treatments using retroviral gene therapy. Due to the risk of oncogenesis caused by retroviral insertional activation of host genes, most of the efforts ..
  99. pmc Viral vectors for neurotrophic factor delivery: a gene therapy approach for neurodegenerative diseases of the CNS
    Seung T Lim
    Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, United States
    Pharmacol Res 61:14-26. 2010
    ..In this review, we discuss viral vector-mediated gene transfer of NTFs to treat neurodegenerative diseases of the central nervous system...
  100. pmc CNS-targeted gene therapy improves survival and motor function in a mouse model of spinal muscular atrophy
    Marco A Passini
    Genzyme Corporation, 49 New York Avenue, Room 2410, Framingham, MA 01701, USA
    J Clin Invest 120:1253-64. 2010
    ..that leads to earlier onset of gene expression compared with standard AAV vectors - led to improved efficacy of gene therapy, including a substantial extension in median survival to 157 days...
  101. ncbi A two-stage poly(ethylenimine)-mediated cytotoxicity: implications for gene transfer/therapy
    S Moein Moghimi
    Molecular Targeting and Polymer Toxicology Group, School of Pharmacy, University of Brighton, Brighton BN2 4GJ, UK
    Mol Ther 11:990-5. 2005
    ..The reported observations have important implications for the design and execution of gene therapy protocols as well for controlling intracellular distribution of drugs with cationic-based polymer-delivery ..

Research Grants77

  1. Non-viral Genetic Modification of Antigen-presenting Cells in Allografts
    Wilson S Meng; Fiscal Year: 2011
    ..In summary, we expect the research to provide strong rationale for testing ex vivo IL-10 gene therapy in transplantation of DC-rich organs to achieve specific immunosuppression...
  2. Sphingolipid Metabolism in Drosophila Development
    Julie D Saba; Fiscal Year: 2013
    ..Skeletal muscle is also a prime target organ for gene therapy, since engineered myoblasts can be made to fuse with mature muscle, generating a stable hybrid organ within the ..
    David Allen; Fiscal Year: 2009
    ..commonly referred to as biologics) include vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, monoclonal antibodies, and recombinant therapeutic proteins that are used to treat or protect humans ..
  4. Pathobiology of Cystic Fibrosis-Related Diabetes in a Ferret Model
    Zoe Stewart; Fiscal Year: 2013
    ..of cystic fibrosis (CF) and strategies to utilize recombinant adenovirus-associated viruses (rAAV) as gene therapy vectors. Dr...
  5. Twenty-second Annual Fanconi Anemia Research Fund Scientific Symposium
    GROVER CARLTON BAGBY; Fiscal Year: 2010
    ..The disease is an ideal candidate for gene therapy because of the inherent selectability of complemented stem cells...
  6. 24th Annual Fanconi Anemia Research Fund Scientific Symposium
    GROVER CARLTON BAGBY; Fiscal Year: 2012
    ..The disease is an ideal candidate for gene therapy because of the inherent selectability of complemented stem cells...
  7. Gene Therapy with Cardiotropic Vectors for the Treatment of Heart Failure
    Roger J Hajjar; Fiscal Year: 2013
    ..a program of targeting important calcium cycling proteins which has led to the first in man clinical trial of gene therapy for heart failure using adeno-associated type 1 (AAV) vector carrying the cardiac Sarcoplasmic Reticulum ..
  8. Present Homologous and Heterologous Antigen with Hepatitis E Virus
    R Holland Cheng; Fiscal Year: 2012
    ..with Dr Kit Lam and Dr Christopher Walker, two experts respectively in drug discovery and HBV vaccine development, we expect to obtain sufficient data leading us to repeated use of HEV-VLPs as carrier for clinical gene therapy.
  9. Antibody-mediated Gene Therapy for the Treatment of Cancer
    TRACY RUTH DANIELS-WELLS; Fiscal Year: 2013 applicant): The proposed studies focus on the development and characterization of new highly targeted gene therapy approaches for the systemic treatment of aggressive B-cell lymphomas with an emphasis on mantle cell lymphoma (..
  10. Impaired mitochondrial fusion in pulmonary arterial hypertension
    Stephen L Archer; Fiscal Year: 2010
    ..Indeed, when first cloned, mitofusin-2 was named hyperplasia suppressor gene. Mitofusin-2 gene therapy reduces intimal hyperplasia in a systemic arterial injury model...
    J Evan Sadler; Fiscal Year: 2013
    ..include: pathogenesis of hemorrhagic and thrombotic disorders;regulation of blood coagulation and fibrinolysis;gene therapy of hemophilia and lysosomal storage diseases;phosphoinositide metabolism and cell signaling pathways;mechanisms ..
  12. Retroviral Vector-mediated Liver Gene Therapy for MPS I
    Katherine P Ponder; Fiscal Year: 2013
    ..The development of an effective and safe gene therapy for MPS I could have a dramatic positive impact on the lives of patients and the families that care for them...
  13. Mechanism of Irradiation Pulmonary Fibrosis
    Joel S Greenberger; Fiscal Year: 2012
    ..are significantly reduced by intrapulmonary manganese superoxide dismutase-plasmid liposome (MnSOD-PL) gene therapy. We now propose to elucidate the cellular and molecular mechanism(s) of initiation of the late pulmonary lesion ..
  14. A Ribozyme Rescue Strategy for Dry Age-Related Macular Degeneration
    John M Sullivan; Fiscal Year: 2013
    ..The long term objective is to develop a safe and effective gene therapy for dAMD/JMD...
  15. Mechanisms of Diabetic Hyperphagia and Insulin Resistance
    Michael W Schwartz; Fiscal Year: 2012
    ..Specifically, we will use a combination of Cre-loxP genetic and adenoviral gene therapy techniques to increase PKB specifically in NPY/Agrp neurons, POMC neurons, neurons that express leptin ..
  16. Neonatal Chemoselection Following Ex Vivo Gene Transfer For Hereditary Disorders
    KARIN L GAENSLER; Fiscal Year: 2012 disease (GVHD). Hurdles to the application of gene therapy for hereditary disorders include variable gene expression, inefficient transduction of HSC, and immune ..
  17. CTL response to AAV Vector
    Richard J Samulski; Fiscal Year: 2013
    Adeno-associated virus (AAV) is a very promising gene therapy vector in pre-clinical and clinical trials...
  18. New Molecular and Cellular Mechanisms of Glaucoma
    Andrei Surguchov; Fiscal Year: 2013
    ..described in Specific Aim 2will be a base for translational studies aimed at the treatment of glaucoma by gene therapy. PUBLIC HEALTH RELEVANCE: Glaucoma is the second leading cause of blindness worldwide...
  19. Macrophage-based Human Gene Therapy for Hereditary PAP
    Bruce C Trapnell; Fiscal Year: 2012
    ..will be tested in 3 Specific Aims: (1) macrophage-mediated cell therapy of hPAP in mice;(2) macrophage-mediated gene therapy of hPAP in mice;(3) preclinical correction of CSF2RA expression and surfactant catabolism in macrophages from ..
  20. Inhibition of matrix proteases to sensitize medulloblastoma cells to radiation
    Andrei L Gartel; Fiscal Year: 2013
    ..b>Gene therapy consists of the introduction of genetic material into diseased cellular targets to bring about therapeutic ..
  21. Engineering the Brain Immune System for Tumor Therapy
    Maria G Castro; Fiscal Year: 2013 intracranial brain tumor model we have shown that a novel combined conditional cytotoxic/immune-stimulatory gene therapy eliminates the growing tumor, and induces immunological memory which protects animals from tumor recurrence...
  22. Optimization of adoptive immunotherapy with autologous CD20-specific T cells
    Brian Till; Fiscal Year: 2013 well as managing the many other facets of a gene therapy trial as principal investigator...
  23. Non-viral gene therapy for sickle cell anemia
    CLIFFORD JOHN STEER; Fiscal Year: 2012
    ..To accomplish our objective, we propose an R21/R33 phased innovation grant application using a novel non- viral gene therapy that will be optimized in transgenic sickle mice and ultimately tested in patients with SCA...
  24. Intravenous Protein Therapy for Myotonic Dystrophy Type 1
    Richard Weisbart; Fiscal Year: 2010
    ..association through small-molecule and nucleotide-based therapies, [3] transgenic overexpression of MBNL1 via gene therapy, and [4] direct intravenous application of exogenous MBNL1...
  25. DNA Methylation Control Hematopoietic Stem Cell Lineage Differentiation
    GRANT ANTHONY CHALLEN; Fiscal Year: 2013
    ..As part of the Center for Cell and Gene Therapy (CAGT) and the Stem Cells and Regenerative Medicine (STaR) Center, I will have access to diverse core ..
  26. Double Humanization of Liver and Blood in Mice
    ELIZABETH MARIE WILSON; Fiscal Year: 2012
    ..drug metabolism and pharmacokinetics, drug-drug interactions, toxicology and gene therapy among others...
  27. Over-Expression of microRNA-126 in Macrophages for Treatment of Atherosclerosis
    Suzette Laing; Fiscal Year: 2013
    ..detrimental genes in macrophages, or using the macrophage as a delivery mechanism is gaining attention in the gene therapy field...
  28. Twenty-first Annual Fanconi Anemia Research Fund Scientific Symposium
    Grover Bagby; Fiscal Year: 2009
    ..The disease is an ideal candidate for gene therapy because of the inherent selectability of complemented stem cells...
  29. Role in Myopia Development of Retinal Pigment Epithelium - A New Therapeutic Targ
    Yan Zhang; Fiscal Year: 2013
    ..BMPs) in eye growth regulation and myopia development, with the RPE targeted in related exploratory studies of gene therapy for myopia treatment. Over the course of her studies to-date, Dr...
  30. Aqueous humor dynamics studies in vivo and in vitro
    PAUL LEON KAUFMAN; Fiscal Year: 2010
    ..b>Gene therapy approaches will be utilized to lower IOP by enhancing outflow via the uveoscleral pathway...
  31. Gene Therapy for Retinitis Pigmentosa
    Rajendra Kumar-Singh; Fiscal Year: 2012
    ..This is in stark contrast to the success gene therapy approaches have had in other ocular tissues such as the retinal pigment epithelium (RPE) and specifically in ..
  32. Gene-Engineered and Targeted Stem Cell Therapy for Myeloma
    Selvarangan Ponnazhagan; Fiscal Year: 2013
    ..By combining the OPG therapy with tumor-targeted chemotherapy and tumor vasculature-targeted anti-angiogenic gene therapy we seek to establish a novel treatment paradigm for MM in a preclinical mouse model...
  33. Gene-Targeted Pro-Drug Therapy for Colorectal Cancer
    Hiremagalur N Jayaram; Fiscal Year: 2013
    ..that design of targeted therapy for colorectal cancer is possible by a two-step approach which combines gene therapy to enhance metabolism of a pro-drug, Tiazofurin within cancer cells following therapy...
  34. Mechanisms of Pleural Fibrosis in Empyema
    Kamal A Mohammed; Fiscal Year: 2013 pharmacological means to prevent fibrosis in pleural empyema;2) via targeting miR-26a by intrapleural gene therapy to prevent fibrosis in pleural empyema...
  35. Lentiviral-transduced hematopoictic stem cell transplantation for cystinosis
    Stephanie Cherqui; Fiscal Year: 2013
    ..This work represents the first stem cell and gene therapy treatment strategies for cystinosis and builds the foundations for a future clinical trial...
    HYUNG D RYOO; Fiscal Year: 2010
    ..Tools to manipulate cells'secretory capacity may be used to enhance production of recombinant proteins in cultured cells or in gene therapy or cell therapy in vivo.
  37. Gene therapy to support cone metabolism in retinitis pigmentosa
    Constance L Cepko; Fiscal Year: 2013
    ..As an alternative, gene therapy can be used to attack a problem common to multiple genetic forms of blindness...
  38. Experimental Optic Neuritis: Gene Therapy
    John Guy; Fiscal Year: 2011
    During the past grant cycle, our gene therapy studies showed that genes encoding enzymes that detoxify reactive oxygen species (ROS) have a protective effect on suppressing experimental allergic encephalomyelitis (EAE), an animal model ..
  39. Novel therapy for monoamine neurotransmitter deficiency in PKU
    Cary O Harding; Fiscal Year: 2013
    ..through dietary phenylalanine restriction or recombinant adeno-associated virus (rAAV)- mediated liver-directed gene therapy. In the final aim of the project, we will investigate, using microdialysis methods, whether acute ..
  40. Bioengineering of Novel Synthetic Lipid-Peptide Lung Surfactants
    Robert H Notter; Fiscal Year: 2013
    ..use of synthetic surfactants to facilitate the delivery of exogenous DNA to animals with lung injury for future gene therapy or multi-drug therapy applications...
  41. Genetic correction of human beta-thalassemic induced pluripotent stem cells
    EIRINI PAPAPETROU; Fiscal Year: 2012
    ..stem cell technology, this proof-of-principle study can provide a new paradigm of integrated iPS-based cell and gene therapy, generally applicable to genetic disorders and advance this new field towards translation to the clinic...
    Jay A Nelson; Fiscal Year: 2012
    ..immune response, transcriptional control, regulation of gene expression, chemotherapeutic targets, and virus gene therapy. Public Health Relevance: The International Herpesvirus Workshop is the premier scientific meeting for ..
  43. Dysfunction of neurofilaments in disease: an iPS model of Giant Axonal Neuropathy
    ..determine if replacement of gigaxonin can reverse any GAN-related phenotypes, as a first proof of concept for gene therapy. GAN and control iPSCs will be differentiated into MNs and characterized for MN markers and activity...
  44. Striated Muscle Gene Transcription and Regulatory Gene Cassettes for Gene Therapy
    ..Aims 1 &2, as well as control regions from other muscle genes, to design optimal regulatory cassettes for gene therapy. Proteins expressed from these cassettes could be used for treating muscle diseases, muscle aging &injury ..
  45. Nanodiagnostics and Nanotherapeutics: Building Research Ethics and Oversight
    Susan M Wolf; Fiscal Year: 2010
    ..This 2-year project will examine current and emerging nanomedicine research on drugs, devices, and gene therapy in order to map the issues raised by nanodiagnostic and nanotherapeutic research and oversight and formulate ..
  46. Development of CNS-targeted AAV vectors
    MIGUEL S ESTEVES; Fiscal Year: 2012
    ..However development of gene therapy approaches for many other neurological diseases will require global gene delivery to the CNS...
  47. Identification of Disease-Causing Mutations in SCID Using Exome-Wide Sequencing
    Joseph L Roberts; Fiscal Year: 2010
    ..cohort of 29 patients is crucial for: 1) better understanding of immune system development and function;2) genetic counseling and prenatal diagnosis;and 3) possible future application of gene therapy to the treatment of these infants.
  48. Gutless Adenovirus Mediated Gene Therapy for Glioma
    Maria G Castro; Fiscal Year: 2011
    ..We have tested in a large syngeneic rodent intracranial glioma model a combined gene therapy approach using first generation recombinant adenovirus vectors expressing fms-like tyrosine kinase 3 ligand (..
  49. Stem cells for novel gene delivery of nitric oxide in the gut
    Hiroshi Mashimo; Fiscal Year: 2013
    ..therapy as has been the initial focus for their use, but as a novel means of chronic and local drug delivery or gene therapy in the adult gastrointestinal tract...
  50. Unfolded Protein Response as a Therapeutic Target for ADRP Animal Models
    Marina Gorbatyuk; Fiscal Year: 2013
    ..Protein Response (UPR) in autosomal dominant retinitis pigmentosa (ADRP) pathogenesis and development of the gene therapy based on modulation of the UPR signaling markers...
    Jay A Nelson; Fiscal Year: 2011
    ..immune response, transcriptional control, regulation of gene expression, chemotherapeutic targets, and virus gene therapy. PUBLIC HEALTH RELEVANCE: The International Herpesvirus Workshop is the premier scientific meeting for ..
  52. Hepatic Non-viral Gene Therapy
    Leaf Huang; Fiscal Year: 2013
    Abstract Many genetic and acquired diseases of the liver can be theoretically treated with gene therapy. The efficiency of non-viral vectors typically falls behind that of viral vectors, except the hydrodynamic injection method...
  53. Identifying the Atoh1 targetome in hair cells with deep sequencing
    Andrew K Groves; Fiscal Year: 2013
    ..For these reasons, Atoh1 has been proposed as tool for gene therapy to replace lost auditory or vestibular hair cells...
  54. Myosin 15:Genetics, Pathology and Therapeutic Potential
    Sally A Camper; Fiscal Year: 2013
    ..We established adenoviral vectors for gene therapy and a database of genes exhibiting differential expression in the cochlea between weaning and adulthood in ..
  55. Regulated Transgene Expression in the Retina
    James M Wilson; Fiscal Year: 2010
    ..Diseases that affect visual acuity have emerged as potential candidates for gene therapy. Direct injection of viral vectors, such as those based on adeno- associated viruses (AAV), into different ..
  56. Protein Therapy for Recessive Dystrophic Epidermolysis Bullosa
    David T Woodley; Fiscal Year: 2010
    ..mouse), we developed four therapeutic strategies to treat RDEB patients - (i) keratinocyte-based ex vivo gene therapy;(ii) fibroblast based-cell therapy;(iii) lentiviral vector-based therapy;and (iv) recombinant C7 protein ..
  57. Novel Approach to Oral Gene Therapy for Chronic Granulomatous Disease
    Peter E Newburger; Fiscal Year: 2010
    ..The results of these studies, if successful, should demonstrate the feasibility of this novel gene therapy system for CGD and would provide a strong basis for large animal studies and translational research to bridge ..
  58. Gene Therapy of Mucopolysaccharidosis VII
    Mark E Haskins; Fiscal Year: 2012
    ..The development of an effective and safe gene therapy for MPS VII could have a dramatic positive impact on the lives of patients and the families that care for them...
  59. Molecular Analysis of Juvenile Hormone Action
    Subba R Palli; Fiscal Year: 2013
    ..receptors identified can also be used in medicine by developing gene switches for various applications such as gene therapy, tissue engineering and therapeutic protein production...
  60. Platelet-Derived FVIII Gene Therapy of Hemophilia A
    Qizhen Shi; Fiscal Year: 2013
    ..Generation of such inhibitors might have the potential to preclude gene therapy for hemophilia A...
  61. Pathogenesis/Treatment-Inherited Cholesterol Deficiency
    Gordon L Watson; Fiscal Year: 2013
    ..Three Specific Aims are proposed: (Aim 1) Define the limitations of post-natal, systemic gene therapy. The ratio of DHC/C is an indicator of SLOS severity...
  62. Gene therapy in the cornea
    RAJIV RAVINDRA MOHAN; Fiscal Year: 2012
    ..5 million Americans each year. Tissue-targeted and localized gene therapy for the cornea offers promise to cure, reduce and/or prevent corneal blindness caused by trauma, injury, ..
    Ronald Crystal; Fiscal Year: 2005
    ..Raffi, S. Worgall, R. Crystal) and 1 at Memorial-Sloan Kettering (M. Sadelain). At the center of our gene therapy program is the Belfer Gene Therapy Core Facility, a 12,000 ft2, state-of-the-art wet laboratory, experimental ..
    Mark Kay; Fiscal Year: 2005
    The following application is to continue support an inter-institutional Program of Excellence in Gene Therapy (PEGT)...
  65. A gene therapy for bacterial translocation in mice with whole body irradiation
    Fujio Suzuki; Fiscal Year: 2010
    ..Severely burned mice were subjected to gene therapy using CCL2 antisense oligodeoxynucleotides (ODN), because these mice early after burn injury were carriers of ..
  66. Pilot Studies of Gene Therapy for Primary Ciliary Dyskinesia
    Lawrence E Ostrowski; Fiscal Year: 2010
    ..Specifically, this application is focused on developing gene therapy as a treatment for the rare disease Primary Ciliary Dyskinesia (PCD)...
  67. Enhancing Suicide Gene Therapy Through Mechanism-Based Approaches
    Donna Shewach; Fiscal Year: 2007
    Suicide gene therapy is an attractive approach to treatment of cancer because it is more selective than traditional cancer chemotherapy...
  68. Gene Therapy for the Hemophilias
    Christopher Walsh; Fiscal Year: 2006
    unreadable] DESCRIPTION (provided by applicant): Effective gene therapy will revolutionize the treatment of the hemophilias...
    Rafael Amado; Fiscal Year: 2002
    ..of this Investigator Award proposal is to consolidate the applicant's career in the field of translational gene therapy research for the treatment of HIV infection...
  70. Retroviral replicating vector for prodrug activator gene therapy
    Douglas J Jolly; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Many strategies for gene therapy of solid tumors involve the use of replication-defective Moloney murine leukemia (MLV)-based retroviral vectors, but efficacy has been limited due to lack of adequate ..
    DANIEL MC BRIDE; Fiscal Year: 2001
    ..caused by mutations in type 1 procollagen genes, is one example of a disease that may benefit from somatic gene therapy. Since bone fragility in 01 is caused by structural mutations in the genes that encode type 1 procollagen, ..
  72. Gene Delivery of P53 in a Tumor-bearing Mouse Model
    ARCHIBALD MIXSON; Fiscal Year: 2007
    ..Although gene therapy with p53 may include several antiturnor mechanisms, antiangiogenesis is one important mechanism by which p53 ..
  73. Sleeping Beauty-mediated Gene Therapy of X-linked SCID
    Kendra A Hyland; Fiscal Year: 2010
    ..These diseases are considered prime candidates for gene therapy by introduction of the missing gene into hematopoietic stem cells that can then differentiate into lymphoid ..
  74. Testing the safety and efficacy of inhibitory RNA mediated purine analog resistan
    Christopher C Porter; Fiscal Year: 2010
    b>Gene therapy has long been touted to hold the promise of cure for a variety of congenital diseases...
  75. Stem Cells as Delivery Vehicles and Imaging Probes for Glioma Gene Therapy
    Syed Ali; Fiscal Year: 2009
    ..b>Gene therapy promises to improve the prognosis of GBM, however, several factors including the lack of an efficient vector ..
  76. Brain Tumor Stem Cell-targeted Gene Therapy
    JOHN OHLFEST; Fiscal Year: 2007
    ..our Sleeping Beauty (SB) Transposon plasmid-based gene transfer system for treatment of brain tumors with INF-? gene therapy. In contrast to conventional plasmid DNA vectors, SB mediates sustained gene expression in glioma cells and ..
    Paul Monahan; Fiscal Year: 2003
    ..virus (AAV) is a dependent parvovirus whose unique biology recommends it as a safe and efficient vector for gene therapy. In the absence of co-infection with a helper virus (adenovirus), the wtAAV integrates and persists in the host ..