Genomes and Genes
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.
Publications293 found, 100 shown here
- The ERBB3 receptor in cancer and cancer gene therapyG 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...
- Results from a phase I safety trial of hAADC gene therapy for Parkinson diseaseJ 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...
- 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.
- A third-generation lentivirus vector with a conditional packaging systemT 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...
- LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1S 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 ..
- Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophyNathalie 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...
- Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1Salima 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. 2008Previously, 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...
- Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemiaMarina Cavazzana-Calvo
Clinical Investigation Center in Biotherapy, Groupe Hospitalier Universitaire Ouest, Inserm Assistance Publique Hôpitaux de Paris, Paris 75015, France
Nature 467:318-22. 2010The 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 ..
- 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...
- 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.
- 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. 2012To 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.
- Restoration of anti-Aspergillus defense by neutrophil extracellular traps in human chronic granulomatous disease after gene therapy is calprotectin-dependentMatteo 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...
- 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..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 ..
- Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous diseaseStefan 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...
- Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigenLaura A Johnson
Surgery Branch, Hatfield Clinical Research Center, National Cancer Institute NIH, Bethesda, MD 20892, USA
Blood 114:535-46. 2009b>Gene therapy of human cancer using genetically engineered lymphocytes is dependent on the identification of highly reactive T-cell receptors (TCRs) with antitumor activity...
- 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.
- Design and development of polymers for gene deliveryDaniel 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. 2005The 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...
- Progress and problems with the use of viral vectors for gene therapyClare E Thomas
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA
Nat Rev Genet 4:346-58. 2003b>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...
- Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trialAlbert M Maguire
F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Lancet 374:1597-605. 2009b>Gene therapy has the potential to reverse disease or prevent further deterioration of vision in patients with incurable inherited retinal degeneration...
- 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. 2010The 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...
- Gene therapy for immunodeficiency due to adenosine deaminase deficiencyAlessandro Aiuti
San Raffaele Telethon Institute for Gene Therapy, Milan, Italy
N Engl J Med 360:447-58. 2009We 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.
- 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].)...
- Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vectorDawn 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...
- Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transferSteven 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 ..
- 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. 2006The 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...
- Zinc-finger nucleases: the next generation emergesToni Cathomen
Institute of Virology CBF, Charite Medical School, Berlin, Germany
Mol Ther 16:1200-7. 2008Methods of modifying the human genome precisely and efficiently hold great promise for revolutionizing the gene therapy arena...
- Progress and prospects: zinc-finger nucleases as gene therapy agentsD 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...
- 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...
- 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 failureMariell 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...
- 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..2%). Vectors based on AAV5, AAV8, and AAV9 may have an advantage for gene therapy in humans...
- AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trialPeter 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...
- Cancer regression in patients after transfer of genetically engineered lymphocytesRichard 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...
- Highly efficient endogenous human gene correction using designed zinc-finger nucleasesFyodor 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-..
- The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapyEugenio Montini
San Raffaele Telethon Institute for Gene Therapy, Via Olgettina 58, 20132 Milan, Italy
J Clin Invest 119:964-75. 2009gamma-Retroviral vectors (gammaRVs), which are commonly used in gene therapy, can trigger oncogenesis by insertional mutagenesis...
- Restoration of NET formation by gene therapy in CGD controls aspergillosisMatteo 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 ..
- Clades of Adeno-associated viruses are widely disseminated in human tissuesGuangping 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. 2004The potential for using Adeno-associated virus (AAV) as a vector for human gene therapy has stimulated interest in the Dependovirus genus...
- Stem-cell gene therapy for the Wiskott-Aldrich syndromeKaan 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...
- Gene therapy in the cornea: 2005--presentRajiv R Mohan
Harry S Truman Memorial Veterans Hospital, 800 Hospital Drive, Columbia, MO 65201, USA
Prog Retin Eye Res 31:43-64. 2012Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders...
- Transgenesis by lentiviral vectors: lack of gene silencing in mammalian embryonic stem cells and preimplantation embryosAlexander 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...
- Production and purification of serotype 1, 2, and 5 recombinant adeno-associated viral vectorsSergei 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...
- Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosaWilliam 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 ..
- Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cellsRonald 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...
- Gene therapy using adeno-associated virus vectorsShyam 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.
- Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase geneLuis G Melo
Department of Medicine, Brigham and Women s Hospital, and Harvard Medical School, Boston, Massachusetts, USA
Circulation 105:602-7. 2002....
- Glucagon-like peptide-1 gene therapy in obese diabetic mice results in long-term cure of diabetes by improving insulin sensitivity and reducing hepatic gluconeogenesisYoung 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...
- 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. 2009Human gene therapy with rAAV2-vector was performed for the RPE65 form of childhood blindness called Leber congenital amaurosis...
- Effective gene therapy with nonintegrating lentiviral vectorsRafael 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...
- Effects of antioxidant gene therapy on retinal neurons and oxidative stress in a model of retinal ischemia/reperfusionYu 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...
- Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanomaAdil 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...
- Efficacy of gene therapy for X-linked severe combined immunodeficiencySalima Hacein-Bey-Abina
Department of Biotherapy, Necker Enfants Malades Hospital, Paris, France
N Engl J Med 363:355-64. 2010The outcomes of gene therapy to correct congenital immunodeficiencies are unknown...
- SERCA2a gene therapy restores microRNA-1 expression in heart failure via an Akt/FoxO3A-dependent pathwayRegalla 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)...
- 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..b>Gene therapy treatment of several mouse and canine models with novel AAV vectors achieved long term phenotypic corrections...
- Restoration of hearing in the VGLUT3 knockout mouse using virally mediated gene therapyOmar 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.
- The mitotic clock in skeletal muscle regeneration, disease and cell mediated gene therapyV 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...
- 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 alveolarizationBernard 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...
- Meganucleases and other tools for targeted genome engineering: perspectives and challenges for gene therapyGeorge Silva
Cellectis Genome Surgery, 102 Avenue Gaston Roussel, Romainville Cedex, France
Curr Gene Ther 11:11-27. 2011The 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 ..
- Mesoangioblast stem cells ameliorate muscle function in dystrophic dogsMaurilio 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...
- 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.)...
- MECP2 isoform-specific vectors with regulated expression for Rett syndrome gene therapyMojgan 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.
- Mesenchymal progenitor cells as cellular vehicles for delivery of oncolytic adenovirusesSvetlana 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...
- Gene therapy using genetically modified lymphocytes targeting VEGFR-2 inhibits the growth of vascularized syngenic tumors in miceDhanalakshmi 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.
- Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's diseaseJ 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...
- Stem and progenitor cell-mediated tumor selective gene therapyK 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....
- Worsening of cardiomyopathy using deflazacort in an animal model rescued by gene therapyIda Luisa Rotundo
Telethon Institute of Genetics and Medicine, Napoli, Italy
PLoS ONE 6:e24729. 2011We have previously demonstrated that gene therapy can rescue the phenotype and extend lifespan in the delta-sarcoglycan deficient cardiomyopathic hamster...
- Toward brain tumor gene therapy using multipotent mesenchymal stromal cell vectorsDaniel Bexell
Lund Stem Cell Center, Lund University, Lund, Sweden
Mol Ther 18:1067-75. 2010b>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...
- A phase I study of aromatic L-amino acid decarboxylase gene therapy for Parkinson's diseaseShin 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.
- Five siRNAs targeting three SNPs may provide therapy for three-quarters of Huntington's disease patientsEdith 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...
- Clinico-pathological rescue of a model mouse of Huntington's disease by siRNAYu 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...
- Progress in developing cationic vectors for non-viral systemic gene therapy against cancerMarie Morille
Inserm U646, Ingenierie de la Vectorisation Particulaire, Universite d Angers, 10, rue André Boquel, 49100 Angers, France
Biomaterials 29:3477-96. 2008Initially, 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...
- Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapyD 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.
- Hematopoietic-stem-cell-based gene therapy for HIV diseaseHans 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.
- In vitro and in vivo gene therapy vector evolution via multispecies interbreeding and retargeting of adeno-associated virusesDirk 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 ..
- Delivering the goods: viral and non-viral gene therapy systems and the inherent limits on cargo DNA and internal sequencesHelen Atkinson
School of Biomedical Sciences, University of Nottingham, Queen s Medical Center, Nottingham NG7 2UH, UK
Genetica 138:485-98. 2010Viruses 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...
- Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophiesAnneke I den Hollander
Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
J Clin Invest 120:3042-53. 2010....
- 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...
- 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 ..
- Emerging potential of transposons for gene therapy and generation of induced pluripotent stem cellsThierry VandenDriessche
Flanders Institute for Biotechnology VIB, Vesalius Research Center, University of Leuven, Leuven, Belgium
Blood 114:1461-8. 2009Effective gene therapy requires robust delivery of the desired genes into the relevant target cells, long-term gene expression, and minimal risks of secondary effects...
- Comprehensive genomic access to vector integration in clinical gene therapyRichard Gabriel
Department of Translational Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany
Nat Med 15:1431-6. 2009Retroviral 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 ..
- Allele-specific silencing of dominant disease genesVictor 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...
- Effects on proliferation and differentiation of multipotent bone marrow stromal cells engineered to express growth factors for combined cell and gene therapyFernando A Fierro
Institute for Regenerative Cures, University of California, Davis, California 95817, USA
Stem Cells 29:1727-37. 2011....
- Long-term phenotypic correction in factor IX knockout mice by using ΦC31 integrase-mediated gene therapyA 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 ..
- Gene therapy using TRAIL-secreting human umbilical cord blood-derived mesenchymal stem cells against intracranial gliomaSeong 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...
- Polyethylenimine-based non-viral gene delivery systemsU Lungwitz
Department of Pharmacy and Chemistry, Pharmaceutical Technology Unit, University of Regensburg, Regensburg, Germany
Eur J Pharm Biopharm 60:247-66. 2005b>Gene therapy has become a promising strategy for the treatment of many inheritable or acquired diseases that are currently considered incurable...
- Long-term preservation of cone photoreceptors and restoration of cone function by gene therapy in the guanylate cyclase-1 knockout (GC1KO) mouseSanford 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...
- Foamy virus vector integration sites in normal human cellsGrant 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.
- Sustained reduction of vein graft neointima formation by ex vivo TIMP-3 gene therapySarah 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...
- Adipose tissue-derived human mesenchymal stem cells mediated prodrug cancer gene therapyLucia 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.
- Lens epithelium-derived growth factor fusion proteins redirect HIV-1 DNA integrationAndrea 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.
- 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 studyMaria Kinali
The Dubowitz Neuromuscular Centre, University College London Institute of Child Health London, London, UK
Lancet Neurol 8:918-28. 2009....
- Recent developments in transposon-mediated gene therapyMario 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 ..
- VEGF gene therapy: therapeutic angiogenesis in the clinic and beyondM 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...
- Gene therapy-directed osteogenesis: BMP-7-transduced human fibroblasts form bone in vivoP H Krebsbach
Center for Biorestoration of Oral Health, University of Michigan, School of Dentistry, Ann Arbor 48109, USA
Hum Gene Ther 11:1201-10. 2000An ex vivo gene therapy strategy was used to achieve localized skeletal regeneration in vivo...
- Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertensionM 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 ..
- Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patientsSteven 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. 2008X-linked SCID (SCID-X1) is amenable to correction by gene therapy using conventional gammaretroviral vectors...
- LEDGF hybrids efficiently retarget lentiviral integration into heterochromatinRik 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...
- Current status of polymeric gene delivery systemsTae Gwan Park
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305 701, Korea
Adv Drug Deliv Rev 58:467-86. 2006b>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...
- Current advances in retroviral gene therapyYoungsuk 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 ..
- Viral vectors for neurotrophic factor delivery: a gene therapy approach for neurodegenerative diseases of the CNSSeung 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...
- CNS-targeted gene therapy improves survival and motor function in a mouse model of spinal muscular atrophyMarco 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...
- A two-stage poly(ethylenimine)-mediated cytotoxicity: implications for gene transfer/therapyS 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 ..
- Non-viral Genetic Modification of Antigen-presenting Cells in AllograftsWilson 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...
- Sphingolipid Metabolism in Drosophila DevelopmentJulie 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 ..
- SUPPORT CONTRACT FOR THE NTP INTERAGENCY CENTER/VALIDATION OF ALT METHODSDavid 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 ..
- Pathobiology of Cystic Fibrosis-Related Diabetes in a Ferret ModelZoe Stewart; Fiscal Year: 2013..of cystic fibrosis (CF) and strategies to utilize recombinant adenovirus-associated viruses (rAAV) as gene therapy vectors. Dr...
- Twenty-second Annual Fanconi Anemia Research Fund Scientific SymposiumGROVER CARLTON BAGBY; Fiscal Year: 2010..The disease is an ideal candidate for gene therapy because of the inherent selectability of complemented stem cells...
- 24th Annual Fanconi Anemia Research Fund Scientific SymposiumGROVER CARLTON BAGBY; Fiscal Year: 2012..The disease is an ideal candidate for gene therapy because of the inherent selectability of complemented stem cells...
- Gene Therapy with Cardiotropic Vectors for the Treatment of Heart FailureRoger 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 ..
- Present Homologous and Heterologous Antigen with Hepatitis E VirusR 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.
- Antibody-mediated Gene Therapy for the Treatment of CancerTRACY RUTH DANIELS-WELLS; Fiscal Year: 2013..by 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 (..
- Impaired mitochondrial fusion in pulmonary arterial hypertensionStephen 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...
- PRE- AND POSTGRADUATE TRAINING IN MOLECULAR HEMATOLOGYJ 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 ..
- Retroviral Vector-mediated Liver Gene Therapy for MPS IKatherine 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...
- Mechanism of Irradiation Pulmonary FibrosisJoel 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 ..
- A Ribozyme Rescue Strategy for Dry Age-Related Macular DegenerationJohn M Sullivan; Fiscal Year: 2013..The long term objective is to develop a safe and effective gene therapy for dAMD/JMD...
- Mechanisms of Diabetic Hyperphagia and Insulin ResistanceMichael 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 ..
- Neonatal Chemoselection Following Ex Vivo Gene Transfer For Hereditary DisordersKARIN L GAENSLER; Fiscal Year: 2012..host disease (GVHD). Hurdles to the application of gene therapy for hereditary disorders include variable gene expression, inefficient transduction of HSC, and immune ..
- CTL response to AAV VectorRichard J Samulski; Fiscal Year: 2013Adeno-associated virus (AAV) is a very promising gene therapy vector in pre-clinical and clinical trials...
- New Molecular and Cellular Mechanisms of GlaucomaAndrei 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...
- Macrophage-based Human Gene Therapy for Hereditary PAPBruce 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 ..
- Inhibition of matrix proteases to sensitize medulloblastoma cells to radiationAndrei L Gartel; Fiscal Year: 2013..b>Gene therapy consists of the introduction of genetic material into diseased cellular targets to bring about therapeutic ..
- Engineering the Brain Immune System for Tumor TherapyMaria G Castro; Fiscal Year: 2013..an 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...
- Optimization of adoptive immunotherapy with autologous CD20-specific T cellsBrian Till; Fiscal Year: 2013..as well as managing the many other facets of a gene therapy trial as principal investigator...
- Non-viral gene therapy for sickle cell anemiaCLIFFORD 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...
- Intravenous Protein Therapy for Myotonic Dystrophy Type 1Richard Weisbart; Fiscal Year: 2010..association through small-molecule and nucleotide-based therapies,  transgenic overexpression of MBNL1 via gene therapy, and  direct intravenous application of exogenous MBNL1...
- DNA Methylation Control Hematopoietic Stem Cell Lineage DifferentiationGRANT 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 ..
- Double Humanization of Liver and Blood in MiceELIZABETH MARIE WILSON; Fiscal Year: 2012..drug metabolism and pharmacokinetics, drug-drug interactions, toxicology and gene therapy among others...
- Over-Expression of microRNA-126 in Macrophages for Treatment of AtherosclerosisSuzette Laing; Fiscal Year: 2013..detrimental genes in macrophages, or using the macrophage as a delivery mechanism is gaining attention in the gene therapy field...
- Twenty-first Annual Fanconi Anemia Research Fund Scientific SymposiumGrover Bagby; Fiscal Year: 2009..The disease is an ideal candidate for gene therapy because of the inherent selectability of complemented stem cells...
- Role in Myopia Development of Retinal Pigment Epithelium - A New Therapeutic TargYan 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...
- Aqueous humor dynamics studies in vivo and in vitroPAUL LEON KAUFMAN; Fiscal Year: 2010..b>Gene therapy approaches will be utilized to lower IOP by enhancing outflow via the uveoscleral pathway...
- Gene Therapy for Retinitis PigmentosaRajendra 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 ..
- Gene-Engineered and Targeted Stem Cell Therapy for MyelomaSelvarangan 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...
- Gene-Targeted Pro-Drug Therapy for Colorectal CancerHiremagalur 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...
- Mechanisms of Pleural Fibrosis in EmpyemaKamal A Mohammed; Fiscal Year: 2013..by pharmacological means to prevent fibrosis in pleural empyema;2) via targeting miR-26a by intrapleural gene therapy to prevent fibrosis in pleural empyema...
- Lentiviral-transduced hematopoictic stem cell transplantation for cystinosisStephanie 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...
- METABOLIC REGULATION IN THE ACUTE PHASEHYUNG 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.
- Gene therapy to support cone metabolism in retinitis pigmentosaConstance L Cepko; Fiscal Year: 2013..As an alternative, gene therapy can be used to attack a problem common to multiple genetic forms of blindness...
- Experimental Optic Neuritis: Gene TherapyJohn Guy; Fiscal Year: 2011During 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 ..
- Novel therapy for monoamine neurotransmitter deficiency in PKUCary 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 ..
- Bioengineering of Novel Synthetic Lipid-Peptide Lung SurfactantsRobert 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...
- Genetic correction of human beta-thalassemic induced pluripotent stem cellsEIRINI 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...
- INTERNATIONAL HERPESVIRUS WORKSHOPJay 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 ..
- Dysfunction of neurofilaments in disease: an iPS model of Giant Axonal NeuropathyBETHANY LESLIE JOHNSON-KERNER; Fiscal Year: 2012..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...
- Striated Muscle Gene Transcription and Regulatory Gene Cassettes for Gene TherapySTEPHEN DENISON HAUSCHKA; Fiscal Year: 2012..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 ..
- Nanodiagnostics and Nanotherapeutics: Building Research Ethics and OversightSusan 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 ..
- Development of CNS-targeted AAV vectorsMIGUEL S ESTEVES; Fiscal Year: 2012..However development of gene therapy approaches for many other neurological diseases will require global gene delivery to the CNS...
- Identification of Disease-Causing Mutations in SCID Using Exome-Wide SequencingJoseph 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.
- Gutless Adenovirus Mediated Gene Therapy for GliomaMaria 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 (..
- Stem cells for novel gene delivery of nitric oxide in the gutHiroshi 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...
- Unfolded Protein Response as a Therapeutic Target for ADRP Animal ModelsMarina 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...
- INTERNATIONAL HERPESVIRUS WORKSHOPJay 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 ..
- Hepatic Non-viral Gene TherapyLeaf Huang; Fiscal Year: 2013Abstract 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...
- Identifying the Atoh1 targetome in hair cells with deep sequencingAndrew 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...
- Myosin 15:Genetics, Pathology and Therapeutic PotentialSally 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 ..
- Regulated Transgene Expression in the RetinaJames 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 ..
- Protein Therapy for Recessive Dystrophic Epidermolysis BullosaDavid 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 ..
- Novel Approach to Oral Gene Therapy for Chronic Granulomatous DiseasePeter 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 ..
- Gene Therapy of Mucopolysaccharidosis VIIMark 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...
- Molecular Analysis of Juvenile Hormone ActionSubba 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...
- Platelet-Derived FVIII Gene Therapy of Hemophilia AQizhen Shi; Fiscal Year: 2013..Generation of such inhibitors might have the potential to preclude gene therapy for hemophilia A...
- Pathogenesis/Treatment-Inherited Cholesterol DeficiencyGordon 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...
- Gene therapy in the corneaRAJIV 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, ..
- WEILL CORNELL PROGRAM OF EXCELLENCE IN GENE THERAPYRonald 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 ..
- GENE THERAPY FOR HEMOPHILIAMark Kay; Fiscal Year: 2005The following application is to continue support an inter-institutional Program of Excellence in Gene Therapy (PEGT)...
- A gene therapy for bacterial translocation in mice with whole body irradiationFujio 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 ..
- Pilot Studies of Gene Therapy for Primary Ciliary DyskinesiaLawrence 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)...
- Enhancing Suicide Gene Therapy Through Mechanism-Based ApproachesDonna Shewach; Fiscal Year: 2007Suicide gene therapy is an attractive approach to treatment of cancer because it is more selective than traditional cancer chemotherapy...
- Gene Therapy for the HemophiliasChristopher Walsh; Fiscal Year: 2006unreadable] DESCRIPTION (provided by applicant): Effective gene therapy will revolutionize the treatment of the hemophilias...
- CLINICAL GENE THERAPY PROGRAM FOR THE TREATMENT OF AIDSRafael 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...
- Retroviral replicating vector for prodrug activator gene therapyDouglas J Jolly; Fiscal Year: 2012DESCRIPTION (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 ..
- BONE MARROW TRANSPLANTATION IN OIM--A GENE THERAPY MODELDANIEL 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, ..
- Gene Delivery of P53 in a Tumor-bearing Mouse ModelARCHIBALD MIXSON; Fiscal Year: 2007..Although gene therapy with p53 may include several antiturnor mechanisms, antiangiogenesis is one important mechanism by which p53 ..
- Sleeping Beauty-mediated Gene Therapy of X-linked SCIDKendra 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 ..
- Testing the safety and efficacy of inhibitory RNA mediated purine analog resistanChristopher C Porter; Fiscal Year: 2010b>Gene therapy has long been touted to hold the promise of cure for a variety of congenital diseases...
- Stem Cells as Delivery Vehicles and Imaging Probes for Glioma Gene TherapySyed Ali; Fiscal Year: 2009..b>Gene therapy promises to improve the prognosis of GBM, however, several factors including the lack of an efficient vector ..
- Brain Tumor Stem Cell-targeted Gene TherapyJOHN 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 ..
- AAV DIRECTED MUSCLE GENE THERAPY FOR HEMOPHILIA BPaul 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 ..