gene transfer techniques

Summary

Summary: The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.

Top Publications

  1. pmc Safety and efficacy of gene transfer for Leber's congenital amaurosis
    Albert M Maguire
    Scheie Eye Institute, University of Pennsylvania, USA
    N Engl J Med 358:2240-8. 2008
  2. 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
  3. ncbi A transposon-mediated gene trap approach identifies developmentally regulated genes in zebrafish
    Koichi Kawakami
    Division of Molecular and Developmental Biology, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411 8540, Japan
    Dev Cell 7:133-44. 2004
  4. ncbi Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges
    Federico Mingozzi
    Center for Cellular and Molecular Therapeutics, The Children s Hospital of Philadelphia, 3501 Civic Center Boulevard, 5th Floor CTRB, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Genet 12:341-55. 2011
  5. 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
  6. 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
  7. 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
  8. 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
  9. pmc Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes
    Kevin D Foust
    Center for Gene Therapy, The Research Institute at Nationwide Children s Hospital, 700 Children s Drive, Columbus, Ohio 43205, USA
    Nat Biotechnol 27:59-65. 2009
  10. 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

Detail Information

Publications285 found, 100 shown here

  1. pmc Safety and efficacy of gene transfer for Leber's congenital amaurosis
    Albert M Maguire
    Scheie Eye Institute, University of Pennsylvania, USA
    N Engl J Med 358:2240-8. 2008
    ..Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA...
  2. 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
    ..Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter...
  3. ncbi A transposon-mediated gene trap approach identifies developmentally regulated genes in zebrafish
    Koichi Kawakami
    Division of Molecular and Developmental Biology, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411 8540, Japan
    Dev Cell 7:133-44. 2004
    ..We propose our gene trap approach should facilitate studies of vertebrate development and organogenesis...
  4. ncbi Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges
    Federico Mingozzi
    Center for Cellular and Molecular Therapeutics, The Children s Hospital of Philadelphia, 3501 Civic Center Boulevard, 5th Floor CTRB, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Genet 12:341-55. 2011
    ..Recent exciting results have raised hopes for the treatment of many other diseases. As we discuss here, the prospects and challenges for AAV gene therapy are to a large extent dependent on the target tissue and the specific disease...
  5. 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
    ..With the growing understanding of polymer gene-delivery mechanisms and continued efforts of creative polymer chemists, it is likely that polymer-based gene-delivery systems will become an important tool for human gene therapy...
  6. 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...
  7. ncbi Effect of gene therapy on visual function in Leber's congenital amaurosis
    James W B Bainbridge
    Institute of Ophthalmology, University College London, London, United Kingdom
    N Engl J Med 358:2231-9. 2008
    ..These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747 [ClinicalTrials.gov].)...
  8. 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...
  9. pmc Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes
    Kevin D Foust
    Center for Gene Therapy, The Research Institute at Nationwide Children s Hospital, 700 Children s Drive, Columbus, Ohio 43205, USA
    Nat Biotechnol 27:59-65. 2009
    ..It may also be useful for rapid postnatal genetic manipulations in basic neuroscience studies...
  10. 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 systems...
  11. 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...
  12. pmc piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells
    Knut Woltjen
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
    Nature 458:766-70. 2009
    ..We anticipate that the unique properties of this virus-independent simplification of iPS cell production will accelerate this field further towards full exploration of the reprogramming process and future cell-based therapies...
  13. pmc AAV-mediated photoreceptor transduction of the pig cone-enriched retina
    C Mussolino
    Telethon Institute of Genetics and Medicine, Naples, Italy
    Gene Ther 18:637-45. 2011
    ..The data presented here on AAV-mediated transduction of the cone-enriched porcine retina may affect the development of gene-based therapies for rare and common severe photoreceptor diseases...
  14. pmc The hyperactive Sleeping Beauty transposase SB100X improves the genetic modification of T cells to express a chimeric antigen receptor
    Z Jin
    Division of Pediatrics, Children s Cancer Hospital, The University of Texas Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, USA
    Gene Ther 18:849-56. 2011
    ..In aggregate, SB100X improves SB transposition in primary human T cells and can be titrated with an SB transposon plasmid to improve the generation of CD19-specific CAR+ T cells...
  15. ncbi Gold nanoparticles in delivery applications
    Partha Ghosh
    Department of Chemistry, University of Massachusetts, Amherst, MA 01003, USA
    Adv Drug Deliv Rev 60:1307-15. 2008
    ..An additional attractive feature of AuNPs is their interaction with thiols, providing an effective and selective means of controlled intracellular release...
  16. pmc Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN
    Kevin D Foust
    Center for Gene Therapy, The Research Institute at Nationwide Children s Hospital, Columbus, Ohio, USA
    Nat Biotechnol 28:271-4. 2010
    ..This demonstration that scAAV9 traverses the blood-brain barrier in a nonhuman primate emphasizes the clinical potential of scAAV9 gene therapy for SMA...
  17. pmc Selection of target sites for mobile DNA integration in the human genome
    Charles Berry
    Department of Family and Preventive Medicine, School of Medicine, University of California San Diego, La Jolla, California, United States of America
    PLoS Comput Biol 2:e157. 2006
    ....
  18. ncbi New recombinant serotypes of AAV vectors
    Guangping Gao
    Division of Medical Genetics, Department of Medicine, University of Pennsylvania School of Medicine, 2000, Translational Research Laboratories, 125S, 31st Street, Philadelphia, PA 19104 3403, USA
    Curr Gene Ther 5:285-97. 2005
    ..Vectors based on new primate AAVs could become the next generation of efficient gene transfer vehicles for various gene therapy applications...
  19. ncbi Efficient in utero gene transfer system to the developing mouse brain using electroporation: visualization of neuronal migration in the developing cortex
    H Tabata
    Department of Molecular Neurobiology, Institute of DNA Medicine, Jikei University School of Medicine, Minato-ku, 105-8461, Tokyo, Japan
    Neuroscience 103:865-72. 2001
    ..Thus, this system is much easier and more efficient than virus-mediated gene transfer, and is useful for gain-of-function analysis of neural cell fate determination, migration, positioning and axon path-finding in mouse embryos...
  20. ncbi Zebrafish enhancer detection (ZED) vector: a new tool to facilitate transgenesis and the functional analysis of cis-regulatory regions in zebrafish
    Jose Bessa
    Centro Andaluz de Biologia del Desarrollo, CSIC Universidad Pablo de Olavide, Campus UPO, Seville, Spain
    Dev Dyn 238:2409-17. 2009
    ..More strikingly, insulator sequences from mouse and chicken, but not conserved in zebrafish, maintain their insulator capacity when tested in this model...
  21. ncbi IRES-dependent second gene expression is significantly lower than cap-dependent first gene expression in a bicistronic vector
    H Mizuguchi
    Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo, Japan
    Mol Ther 1:376-82. 2000
    ..e., care should be taken regarding the decreased capacity of IRES-dependent downstream gene expression as well as in determining which gene should be positioned as the first or second gene in a bicistronic vector...
  22. ncbi Evaluating the biological relevance of putative enhancers using Tol2 transposon-mediated transgenesis in zebrafish
    Shannon Fisher
    McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Nat Protoc 1:1297-305. 2006
    ..This system is amenable to large-scale application, facilitating rapid functional analysis of noncoding sequences from both mammalian and teleost species...
  23. ncbi Exploring polyethylenimine-mediated DNA transfection and the proton sponge hypothesis
    Akin Akinc
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Gene Med 7:657-63. 2005
    ..According to the proton sponge hypothesis, the buffering capacity of PEI leads to osmotic swelling and rupture of endosomes, resulting in the release of the vector into the cytoplasm...
  24. pmc Harnessing a high cargo-capacity transposon for genetic applications in vertebrates
    Darius Balciunas
    The Arnold and Mabel Beckman Center for Transposon Research, Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota, United States of America
    PLoS Genet 2:e169. 2006
    ..Together, Tol2 provides a novel nonviral vector for the delivery of large genetic payloads for gene therapy and other transgenic applications...
  25. pmc Sleeping beauty system to redirect T-cell specificity for human applications
    Sourindra N Maiti
    Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
    J Immunother 36:112-23. 2013
    ..01%. These findings lay the groundwork as the basis of our first-in-human clinical trials of the nonviral SB system for the investigational treatment of CD19 B-cell malignancies (currently under 3 INDs: 14193, 14577, and 14739)...
  26. pmc Agrobacterium-mediated plant transformation: the biology behind the "gene-jockeying" tool
    Stanton B Gelvin
    Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907 1392, USA
    Microbiol Mol Biol Rev 67:16-37, table of contents. 2003
    ..Knowledge of fundamental biological principles embracing both the host and the pathogen have been and will continue to be key to extending the utility of Agrobacterium for genetic engineering purposes...
  27. pmc Retroviral DNA integration: viral and cellular determinants of target-site selection
    Mary K Lewinski
    Infectious Disease Laboratory, The Salk Institute, La Jolla, California, USA
    PLoS Pathog 2:e60. 2006
    ....
  28. 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
    ..In this context, materials, facilitating the design of novel PEI-based non-viral vectors are described...
  29. pmc Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer
    George Buchlis
    Division of Hematology and Center for Cellular and Molecular Therapeutics, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Blood 119:3038-41. 2012
    ..This is the longest reported transgene expression to date from a parenterally administered AAV vector, with broad implications for the future of muscle-directed gene transfer...
  30. pmc Successful attenuation of humoral immunity to viral capsid and transgenic protein following AAV-mediated gene transfer with a non-depleting CD4 antibody and cyclosporine
    J H McIntosh
    Department of Haematology, UCL Cancer Institute, University College London, Oxford, UK
    Gene Ther 19:78-85. 2012
    ..These observations could significantly improve the prospects of using rAAV vectors for chronic disorders by allowing for repeated vector administration and avoiding the development of antibodies to the transgene product...
  31. pmc High-resolution labeling and functional manipulation of specific neuron types in mouse brain by Cre-activated viral gene expression
    Sandra J Kuhlman
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America
    PLoS ONE 3:e2005. 2008
    ....
  32. pmc Systemic gene delivery in large species for targeting spinal cord, brain, and peripheral tissues for pediatric disorders
    Adam K Bevan
    Center for Gene Therapy, The Research Institute at Nationwide Children s Hospital, Columbus, Ohio 43205, USA
    Mol Ther 19:1971-80. 2011
    ..Our findings support the use of AAV9 for gene transfer to the CNS for disorders in pediatric populations...
  33. ncbi Low-molecular-weight polyethylenimine as a non-viral vector for DNA delivery: comparison of physicochemical properties, transfection efficiency and in vivo distribution with high-molecular-weight polyethylenimine
    Klaus Kunath
    Department of Pharmaceutics and Biopharmacy, Philipps University of Marburg, Ketzerbach 63, D 35032, Marburg Lahn, Germany
    J Control Release 89:113-25. 2003
    ....
  34. 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...
  35. ncbi A multifunctional envelope type nano device (MEND) for gene delivery to tumours based on the EPR effect: a strategy for overcoming the PEG dilemma
    Hiroto Hatakeyama
    Faculty of Pharmaceutical Sciences, Hokkaido University, Japan
    Adv Drug Deliv Rev 63:152-60. 2011
    ....
  36. ncbi High efficiency gene transfer using chitosan/DNA nanoparticles with specific combinations of molecular weight and degree of deacetylation
    Marc Lavertu
    Department of Chemical Engineering, Institute of Biomedical Engineering, Ecole Polytechnique of Montreal, P O Box 6079, Station Centre Ville, Montreal, Que, Canada H3C 3A7
    Biomaterials 27:4815-24. 2006
    ....
  37. ncbi Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives
    Michael Neu
    Department of Pharmaceutics and Biopharmacy, Philipps University, Ketzerbach 63, 35037 Marburg, Germany
    J Gene Med 7:992-1009. 2005
    ..Rational design of optimized polycations is an objective for further research and may provide the basis for a successful cationic polymer-based gene delivery system in the future...
  38. ncbi CD8(+) T-cell responses to adeno-associated virus capsid in humans
    Federico Mingozzi
    The Children s Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA
    Nat Med 13:419-22. 2007
    ..In addition, we show that AAV-2 induced human T cells proliferate upon exposure to alternate AAV serotypes, indicating that other serotypes are unlikely to evade capsid-specific immune responses...
  39. ncbi Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5
    J M Bergelson
    Division of Infectious Diseases, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 275:1320-3. 1997
    ..Identification of CAR as a receptor for these two unrelated and structurally distinct viral pathogens is important for understanding viral pathogenesis and has implications for therapeutic gene delivery with adenovirus vectors...
  40. ncbi Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo
    F Scherer
    Technische Universitat Munchen, Institute of Experimental Oncology, Munich, Germany
    Gene Ther 9:102-9. 2002
    ..Magnetofection provides a novel tool for high throughput gene screening in vitro and can help to overcome fundamental limitations to gene therapy in vivo...
  41. pmc Neutralizing antibodies against AAV serotypes 1, 2, 6, and 9 in sera of commonly used animal models
    Kleopatra Rapti
    Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA
    Mol Ther 20:73-83. 2012
    ..Our results suggest that prescreening of animals for neutralizing antibodies will be important for future gene transfer experiments in these animal models...
  42. pmc The use of inhibitors to study endocytic pathways of gene carriers: optimization and pitfalls
    Dries Vercauteren
    Laboratory of General Biochemistry and Physical Pharmacy, Department of Pharmaceutics, Ghent University, Ghent, Belgium
    Mol Ther 18:561-9. 2010
    ..Finally, we demonstrate that any inhibitory effects are highly cell line dependent. Overall, the data question the significance of performing endocytosis studies with these agents in the absence of very stringent controls...
  43. pmc Sustained miRNA-mediated knockdown of mutant AAT with simultaneous augmentation of wild-type AAT has minimal effect on global liver miRNA profiles
    Christian Mueller
    Department of Pediatrics and Gene Therapy Center, UMass Medical School, Worcester, Massachusetts 01605, USA
    Mol Ther 20:590-600. 2012
    ..This safe dual-therapy approach can be applied to other disorders such as amyotrophic lateral sclerosis, Huntington disease, cerebral ataxia, and optic atrophies...
  44. ncbi Math1 gene transfer generates new cochlear hair cells in mature guinea pigs in vivo
    Kohei Kawamoto
    Kresge Hearing Research Institute, Department of Otolaryngology, The University of Michigan, Ann Arbor, Michigan 48109 0648, USA
    J Neurosci 23:4395-400. 2003
    ....
  45. ncbi Reversal of cardiac dysfunction after long-term expression of SERCA2a by gene transfer in a pre-clinical model of heart failure
    Yoshiaki Kawase
    Mount Sinai School of Medicine, New York, New York 10029, USA
    J Am Coll Cardiol 51:1112-9. 2008
    ..The aim of this study was to examine the effects of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) gene transfer in a swine heart failure (HF) model...
  46. pmc Efficient production of germline transgenic chickens using lentiviral vectors
    Michael J McGrew
    Roslin Institute, Roslin, Midlothian EH25 9PS, UK
    EMBO Rep 5:728-33. 2004
    ....
  47. ncbi Immune responses to AAV in clinical trials
    Federico Mingozzi
    Children s Hospital of Philadelphia, PA 19104, USA
    Curr Gene Ther 11:321-30. 2011
    ....
  48. ncbi Development of hyperactive sleeping beauty transposon vectors by mutational analysis
    Hatem Zayed
    Max Delbruck Center for Molecular Medicine, Robert Rössle Strasse10, D 13092 Berlin, Germany
    Mol Ther 9:292-304. 2004
    ..The improved vector system should prove useful for efficient gene transfer in vertebrates...
  49. pmc Induction of immune tolerance to coagulation factor IX antigen by in vivo hepatic gene transfer
    Federico Mingozzi
    Department of Pediatrics, The Children s Hospital of Philadelphia, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA
    J Clin Invest 111:1347-56. 2003
    ..With a strain-dependent rate of success, tolerance to murine F.IX was induced in mice with a large F.IX gene deletion, supporting the relevance of these data for treatment of hemophilia B and other genetic diseases...
  50. ncbi Electroporation gene therapy preclinical and clinical trials for melanoma
    Loree C Heller
    Frank Reidy Research Center for Bioelectrics, Old Dominion University, 4211 Monarch Way, Suite 300, Norfolk, VA 23508, USA
    Curr Gene Ther 10:312-7. 2010
    ..This review discusses preclinically tested electroporation gene therapies for melanoma with clinical potential and the conversion of these therapies to clinical trials...
  51. pmc Novel AAV serotypes for improved ocular gene transfer
    Corinna Lebherz
    Gene Therapy Program, Division of Medical Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    J Gene Med 10:375-82. 2008
    ..We show here that AAV7 and 8 enable superior long-term transduction of retinal and also anterior chamber structures...
  52. ncbi Ex vivo gene transfer and correction for cell-based therapies
    Luigi Naldini
    HSR TIGET, San Raffaele Telethon Institute for Gene Therapy and Vita Salute San Raffaele University, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy
    Nat Rev Genet 12:301-15. 2011
    ..As these approaches marry with our growing capacity for genetic reprogramming of mammalian cells, they may fulfil the promise of safe and effective therapies for currently untreatable diseases...
  53. ncbi Minicircle DNA vectors devoid of bacterial DNA result in persistent and high-level transgene expression in vivo
    Zhi Ying Chen
    Department of Pediatrics and Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA
    Mol Ther 8:495-500. 2003
    ..Our data suggest that minicircles are capable of expressing high and persistent levels of therapeutic products in vivo and have a great potential to serve as episomal vectors for the treatment of a wide variety of diseases...
  54. ncbi A hybrid vector for ligand-directed tumor targeting and molecular imaging
    Amin Hajitou
    Department of Genitourinary Medical Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Cell 125:385-98. 2006
    ..This new class of targeted hybrid viral particles will enable a wide range of applications in biology and medicine...
  55. ncbi Gene transfer into genomes of human cells by the sleeping beauty transposon system
    Aron M Geurts
    Department of Genetics, Cell Biology and Development and The Arnold and Mabel Beckman Center for Transposon Research, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Mol Ther 8:108-17. 2003
    ..With the recently described improvements to the transposon itself, the SB system appears to be a potential gene-transfer tool for human gene therapy...
  56. ncbi Gene delivery by lentivirus vectors
    Adam S Cockrell
    Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Mol Biotechnol 36:184-204. 2007
    ..Concluding remarks address some of the successes in preclinical animals, and the recent transition of lentiviral vectors to human clinical trials as therapy for a variety of infectious and genetic diseases...
  57. pmc Gene transfer efficiency and genome-wide integration profiling of Sleeping Beauty, Tol2, and piggyBac transposons in human primary T cells
    Xin Huang
    Division of Pediatric Blood and Marrow Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota, USA
    Mol Ther 18:1803-13. 2010
    ....
  58. ncbi Lung-directed gene therapy in mice using the nonviral Sleeping Beauty transposon system
    Lalitha R Belur
    The Arnold and Mabel Beckman Center for Transposon Research, Institute of Human Genetics, Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA
    Nat Protoc 2:3146-52. 2007
    ..The procedure can be completed within 24 h, starting from preparation of DNA-PEI complexes to analysis of transient transgene expression...
  59. ncbi Ultrasound-based nonviral gene delivery induces bone formation in vivo
    D Sheyn
    Skeletal Biotech Laboratory, Hebrew University of Jerusalem, Jerusalem, Israel
    Gene Ther 15:257-66. 2008
    ..We conclude that ultrasound-mediated osteogenic gene delivery could serve as a therapeutic solution in conditions requiring bone tissue regeneration after further development that will increase the transfection efficiency...
  60. ncbi Purification of polyethylenimine polyplexes highlights the role of free polycations in gene transfer
    Sabine Boeckle
    Pharmaceutical Biology Biotechnology, Department of Pharmacy, Ludwig Maximilians Universitat, Butenandtstr 5 13, D 81377 Munich, Germany
    J Gene Med 6:1102-11. 2004
    ..Nonviral vectors based on polyethylenimine (PEI) usually contain an excess of PEI that is not complexed to DNA. Since unbound PEI contributes to cellular and systemic toxicity, purification of polyplexes from unbound PEI is desirable...
  61. 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
    ....
  62. ncbi Chitosan-DNA nanoparticles as non-viral vectors in gene therapy: strategies to improve transfection efficacy
    Sania Mansouri
    Laboratoire de Recherche en Orthopédie, Hôpital du Sacré Coeur, Montreal, Quebec, Canada
    Eur J Pharm Biopharm 57:1-8. 2004
    ..The objective of this paper was to summarize the state of the art in gene therapy and particularly the use of chitosan to improve the transfection efficiency in vivo and in vitro...
  63. pmc Tropism and toxicity of adeno-associated viral vector serotypes 1, 2, 5, 6, 7, 8, and 9 in rat neurons and glia in vitro
    Douglas B Howard
    Neural Protection and Regeneration Section, Molecular Neuropsychiatry Branch, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, USA
    Virology 372:24-34. 2008
    ..Collectively, a differential tropism and toxicity was observed among the AAV serotypes on primary cortical cultures with an overall preferential glial transduction and toxicity...
  64. ncbi RNA as a source of transposase for Sleeping Beauty-mediated gene insertion and expression in somatic cells and tissues
    Andrew Wilber
    The Arnold and Mabel Beckman Center for Transposon Research, University of Minnesota, Minneapolis, MN 55455, USA
    Mol Ther 13:625-30. 2006
    ..We conclude that in vitro-transcribed mRNA can be used as an effective source of transposase for SB-mediated transposition in mammalian cells and tissues...
  65. ncbi The innate immune response to adenovirus vectors
    Daniel A Muruve
    Department of Medicine, University of Calgary, Calgary, AB, T2N 4N1 Canada
    Hum Gene Ther 15:1157-66. 2004
    ..This review aims to describe data examining cellular and molecular mechanisms involved in the adenovirus-mediated innate immune response...
  66. ncbi Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras
    James O McNamara
    Duke Center for Translational Research, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
    Nat Biotechnol 24:1005-15. 2006
    ..These studies demonstrate an approach for targeted delivery of siRNAs with numerous potential applications, including cancer therapeutics...
  67. ncbi Efficient gene delivery and gene expression in zebrafish using the Sleeping Beauty transposon
    Ann E Davidson
    The Arnold and Mabel Beckman Center for Transposon Research, Institute of Human Genetics, University of Minnesota, Minneapolis, MN 55455, USA
    Dev Biol 263:191-202. 2003
    ....
  68. pmc Site-directed transposon integration in human cells
    Stephen R Yant
    Department of Pediatrics and Genetics, Stanford University School of Medicine, Stanford, CA 94305 5208, USA
    Nucleic Acids Res 35:e50. 2007
    ..These findings illustrate the feasibility of directed transposon integration and highlight potential means for future development...
  69. pmc Nonviral gene delivery: what we know and what is next
    Xiang Gao
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA
    AAPS J 9:E92-104. 2007
    ..A brief discussion of future development and further improvement of the current systems is intended to stimulate new ideas and encourage rapid advancement in this new and promising field...
  70. pmc Efficacy and safety of long-term prophylaxis in severe hemophilia A dogs following liver gene therapy using AAV vectors
    Denise E Sabatino
    Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Mol Ther 19:442-9. 2011
    ..These data demonstrate that both approaches are safe and achieve dose-dependent therapeutic levels of FVIII expression, which supports translational studies of AAV-mediated delivery for HA...
  71. pmc Exogenous and cell surface glycosaminoglycans alter DNA delivery efficiency of arginine and lysine homopeptides in distinctly different ways
    Rangeetha J Naik
    Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India
    J Biol Chem 286:18982-93. 2011
    ..Our results indicate that the role of both the cell surface and exogenous glycosaminoglycans in gene delivery is controlled by the nature of the peptide and its complex with DNA...
  72. ncbi Subretinal delivery of recombinant AAV serotype 8 vector in dogs results in gene transfer to neurons in the brain
    Knut Stieger
    INSERM U649, CHU Hotel Dieu, Nantes, France
    Mol Ther 16:916-23. 2008
    ..Vector sequences were detected in many parts of the brain, but chiefly in the contralateral hemisphere...
  73. ncbi Gene therapy for primary immunodeficiencies: Part 2
    Alessandro Aiuti
    San Raffaele Telethon Institute for Gene Therapy HSR TIGET, Division of Regenerative Medicine, San Raffaele Scientific Institute, Milan, Italy
    Curr Opin Immunol 24:585-91. 2012
    ..In this review we present the status of gene therapy for WAS and CGD, and discuss the emerging application of similar strategies to a broader range of PIDs, such as IPEX syndrome...
  74. pmc Efficient gene delivery and selective transduction of glial cells in the mammalian brain by AAV serotypes isolated from nonhuman primates
    Patricia A Lawlor
    Department of Molecular Medicine and Pathology, The University of Auckland, Auckland, New Zealand
    Mol Ther 17:1692-702. 2009
    ....
  75. pmc Comparative analysis of the recently discovered hAT transposon TcBuster in human cells
    Lauren E Woodard
    Department of Medicine, Division of Nephrology, Baylor College of Medicine, Houston, Texas, USA
    PLoS ONE 7:e42666. 2012
    ..TcBuster, a novel hAT-family transposon system derived from the red flour beetle Tribolium castaneum, was shown to be highly active in previous studies in insect embryoes...
  76. ncbi Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia: phase II results of the Kuopio
    Marja Hedman
    A I Virtanen Institute, University of Kuopio, PO Box 1627, FIN 70211 Kuopio, Finland
    Circulation 107:2677-83. 2003
    ..However, only limited data are available about local VEGF gene transfer given during angioplasty (PTCA) and stenting...
  77. ncbi Systemic delivery systems of angiogenic gene by novel bubble liposomes containing cationic lipid and ultrasound exposure
    Yoichi Negishi
    Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432 1 Horinouchi, Hachioji, Tokyo 192 0392, Japan
    Mol Pharm 9:1834-40. 2012
    ..The gene delivery system into the ischemic hindlimb using the combination of p-BLs and US exposure could be an effective tool for angiogenic gene therapy via systemic injection...
  78. ncbi Selective gene delivery to cancer cells using an integrated cationic amphiphilic peptide
    Qiong Tang
    Department of Chemical and Biomolecular Engineering, University of Akron, Akron, Ohio 44325, United States
    Langmuir 28:16126-32. 2012
    ..The high specificity and transfection efficiency of the integrated peptide-based vector make it a very promising material for targeted gene delivery in cancer therapy...
  79. pmc Generating transgenic mice from bacterial artificial chromosomes: transgenesis efficiency, integration and expression outcomes
    Margaret L Van Keuren
    Transgenic Animal Model Core, University of Michigan Medical School, 2560 MSRB II, Ann Arbor, MI 48109, USA
    Transgenic Res 18:769-85. 2009
    ..Consistent and reproducible success in BAC transgenesis required the combination of careful DNA purification, the use of polyamine buffer, and sensitive genotyping assays...
  80. pmc Nanoparticle-mediated gene transfer specific to retinal pigment epithelial cells
    Adarsha Koirala
    Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
    Biomaterials 32:9483-93. 2011
    ..Overall, our results demonstrate that NPs can efficiently deliver genes to the RPE and hold great potential for the treatment of RPE-associated diseases...
  81. pmc Adeno-associated virus (AAV) serotype 9 provides global cardiac gene transfer superior to AAV1, AAV6, AAV7, and AAV8 in the mouse and rat
    Lawrence T Bish
    Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Hum Gene Ther 19:1359-68. 2008
    ..AAV9 should be used in rodent cardiac studies and may be the vector of choice for clinical trials of cardiac gene transfer...
  82. ncbi Pigment epithelium-derived factor gene therapy inhibits human pancreatic cancer in mice
    Ryunosuke Hase
    Department of Surgical Oncology, Division of Cancer Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
    Clin Cancer Res 11:8737-44. 2005
    ..The purpose of this study was to investigate whether PEDF gene is a potent tumor suppressor and a potential candidate for cancer gene therapy...
  83. pmc Lentiviral gene transfer into the dorsal root ganglion of adult rats
    Hongwei Yu
    Department of Anesthesiology, Medical College of Wisconsin, 8100 Watertown Plank Rd, Milwaukee, Wisconsin 53226, USA
    Mol Pain 7:63. 2011
    ....
  84. ncbi Highly efficient gene delivery by mRNA electroporation in human hematopoietic cells: superiority to lipofection and passive pulsing of mRNA and to electroporation of plasmid cDNA for tumor antigen loading of dendritic cells
    V F Van Tendeloo
    Laboratory of Experimental Hematology, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
    Blood 98:49-56. 2001
    ..Therefore, electroporation of mRNA-encoding tumor antigens is a powerful technique to charge human dendritic cells with tumor antigens and could serve applications in future DC-based tumor vaccines...
  85. ncbi Paving the way for transgenic schistosomes
    S Beckmann
    Institute for Parasitology, Justus Liebig University, 35392 Giessen, Germany
    Parasitology 139:651-68. 2012
    ....
  86. ncbi Targeted gene delivery to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption
    Qin Huang
    Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
    Exp Neurol 233:350-6. 2012
    ..01). The method by using MRI-guided FUS to induce the local BBB disruption could accomplish effective targeted exogenous gene transfer in CNS. This technique may provide a new option for the treatment of various CNS diseases...
  87. ncbi Role of clathrin- and caveolae-mediated endocytosis in gene transfer mediated by lipo- and polyplexes
    Joanna Rejman
    Institute for Experimental Treatment of Cystic Fibrosis, HSR Scientific Institute, Via Olgettina 58, 20132 Milan, Italy
    Mol Ther 12:468-74. 2005
    ....
  88. pmc Cell-type specific oxytocin gene expression from AAV delivered promoter deletion constructs into the rat supraoptic nucleus in vivo
    Raymond L Fields
    Laboratory of Neurochemistry, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS ONE 7:e32085. 2012
    ..We hypothesize that within this 116 bp domain a repressor exists that inhibits expression specifically in AVP MCNs, thereby leading to the cell-type specific expression of the OXT gene only in the OXT MCNs...
  89. ncbi Directed evolution of novel adeno-associated viruses for therapeutic gene delivery
    M A Bartel
    Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA
    Gene Ther 19:694-700. 2012
    ..Here we outline progress in creating novel classes of AAV variant libraries and highlight the successful isolation of variants with novel and advantageous in vitro and in vivo gene delivery properties...
  90. ncbi Insect cells as a factory to produce adeno-associated virus type 2 vectors
    Masashi Urabe
    Laboratory of Biochemical Genetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Hum Gene Ther 13:1935-43. 2002
    ..This robust system provides a simple, cost-effective method for AAV vector production...
  91. pmc Rapid bacterial artificial chromosome modification for large-scale mouse transgenesis
    Shiaoching Gong
    The Rockefeller University, New York, New York, USA
    Nat Protoc 5:1678-96. 2010
    ..CNS anatomical expression maps of the mice are available to the public at http://www.gensat.org/...
  92. pmc Development of a gene transfer-based treatment for radiation-induced salivary hypofunction
    Bruce J Baum
    National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA
    Oral Oncol 46:4-8. 2010
    ..A Phase I/II clinical trial, using a recombinant adenoviral vector to mediate gene transfer, is currently underway...
  93. ncbi AAV9-mediated erythropoietin gene delivery into the brain protects nigral dopaminergic neurons in a rat model of Parkinson's disease
    Y Q Xue
    Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA
    Gene Ther 17:83-94. 2010
    ..This highlights the importance of using an inducible gene delivery system for EPO gene delivery...
  94. ncbi Polymer-functionalized nanodiamond platforms as vehicles for gene delivery
    Xue Qing Zhang
    Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208, USA
    ACS Nano 3:2609-16. 2009
    ..This platform approach represents an efficient avenue toward gene delivery via DNA-functionalized NDs, and serves as a rapid, scalable, and broadly applicable gene therapy strategy...
  95. ncbi Chemical vectors for gene delivery: uptake and intracellular trafficking
    Chantal Pichon
    Centre de Biophysique Moléculaire CNRS UPR 4301, University of Orléans and Inserm, rue Charles Sadron, 45071 Orleans Cedex 2, France
    Curr Opin Biotechnol 21:640-5. 2010
    ..So, intensive investigations to increase the cytosolic delivery of pDNA and its migration toward nuclear pores make sense to bring the transfection efficiency closer to that of viruses...
  96. ncbi Robust spinal motor neuron transduction following intrathecal delivery of AAV9 in pigs
    T Federici
    Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA 30322, USA
    Gene Ther 19:852-9. 2012
    ..These promising results can be translated to many MN diseases requiring diffuse gene delivery...
  97. ncbi Global gene transfer into the CNS across the BBB after neonatal systemic delivery of single-stranded AAV vectors
    Noriko Miyake
    Department of Biochemistry and Molecular Biology, Division of Gene Therapy Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo 113 8602, Japan
    Brain Res 1389:19-26. 2011
    ..These vectors should prove highly useful for efficient and long-term overexpression or downregulation of genes in CNS and spinal cord and could be a useful means of treating genetic neurological diseases...
  98. pmc N-Alkyl-PEI-functionalized iron oxide nanoclusters for efficient siRNA delivery
    Gang Liu
    Laboratory of Molecular Imaging and Nanomedicine LOMIN, National Institute of Biomedical Imaging and Bioengineering NIBIB, National Institutes of Health NIH, Bethesda, MD 20892, USA
    Small 7:2742-9. 2011
    ..In conclusion, Alkyl-PEI2k-IOs demonstrate highly efficient delivery of siRNA and an innocuous toxic profile, making it a potential carrier for gene therapy...
  99. ncbi Enhancement of magnetic nanoparticle-mediated gene transfer to astrocytes by 'magnetofection': effects of static and oscillating fields
    Mark Pickard
    Cellular and Neural Engineering Group, Institute for Science and Technology in Medicine, Keele University, Staffordshire, ST5 5BG, UK
    Nanomedicine (Lond) 5:217-32. 2010
    ..To assess the feasibility of using magnetic nanoparticles (MNPs) to transfect astrocytes derived for transplantation and determine if transfection efficacy can be enhanced by static and oscillating magnetic fields...
  100. ncbi Efficient generation of transgenic pigs using equine infectious anaemia virus (EIAV) derived vector
    C Bruce A Whitelaw
    Department of Gene Function and Development, Roslin Institute, Roslin, Midlothian EH25 9PS, UK
    FEBS Lett 571:233-6. 2004
    ....
  101. pmc PiggyBac transposon-mediated, reversible gene transfer in human embryonic stem cells
    You Tzung Chen
    Graduate Institute of Clinical Genomics and Graduate Institute of Clinical Medicine, Stem Cell Core Laboratory, NTU Research Center for Medical Excellence, Taipei, Taiwan
    Stem Cells Dev 19:763-71. 2010
    ..We also demonstrate that the integrated piggyBac transposon can be removed and an undisrupted insertion site can be restored, which implies potential applications for its use in gene therapy and genetics studies...

Research Grants72

  1. Collagen X and heparan sulfate proteoglycan in the hematopoietic stem cell niche.
    ELIZABETH G SWEENEY; Fiscal Year: 2012
    ..Cancro and Akintoe (my collaborators), and the numerous faculty members that I will interact with at the many journal club, seminar, and symposiums offered at Penn and the surrounding schools. ..
  2. Transgenesis and Xenotransplantation
    Jorge A Piedrahita; Fiscal Year: 2013
    ....
  3. Targeting Cell Death to Prevent Ventricular Remodeling and Heart Failure
    Abhinav Diwan; Fiscal Year: 2011
    ..abstract_text> ..
  4. A XENOPUS LAEVIS RESEARCH RESOURCE FOR IMMUNOBIOLOGY
    Jacques Robert; Fiscal Year: 2013
    ..We are proposing to continue the maintenance and the development of this unique non-mammalian resource facility for biomedical research for the benefit of the whole scientific community. ..
  5. Serotonin, Autism, and investigating cell types for CNS disorders.
    Joseph D Dougherty; Fiscal Year: 2010
    ..The approach proposed here has the potential to provide those cellular targets for treatments. ..
  6. ROLE OF ENHANCERS REGULATING RENIN GENE EXPRESSION
    CURT DANIEL SIGMUND; Fiscal Year: 2013
    ..These studies will link transcriptional signals regulating the renin gene with physiological endpoints controlling blood pressure and metabolism which may go awry in hypertension. I..
  7. Genetic Regulation of Rhombomere Formation
    CHARLES G SAGERSTROM; Fiscal Year: 2013
    ..g. hematopoiesis). The results from our proposed experiments will therefore be applicable to a broad set of biological processes and human disease conditions. ..
  8. Induced Pluripotent Stem Cells from Swine: application to genetic modification
    ROBERT MICHAEL ROBERTS; Fiscal Year: 2013
    ..As the pig is an important reservoir for Salmonella, the LDLR-/- model will have a dual purpose for both agricultural and biomedical applications. ..
  9. Systematic functional analysis of non-coding sequences in transgenic zebrafish
    Shannon Fisher; Fiscal Year: 2010
    ..Through application of this approach, we aim to establish a paradigm and generate reagents that will aid our understanding of the wealth of information arising out of genome sequencing efforts. ..
  10. EVOLUTIONARY ORIGINS OF IMMUNE-TYPE GENES
    GARY WILLIAM LITMAN; Fiscal Year: 2013
    ....
  11. Alveolar Cell Dysfunction and Pulmonary Fibrosis
    Lisa R Young; Fiscal Year: 2011
    ..Simply put, this proposal will use a powerful genetic mouse model to understand how scarring occurs in the lung, and how scarring in the lung might be prevented. (End of Abstract) ..
  12. Wnt Signaling in Hematopoietic Stem Cell Specification and Leukemia
    WILSON KENDRICK CLEMENTS; Fiscal Year: 2013
    ..Finally, I will use the B-cell transgenic animals as a platform for unbiased discovery of additional mutations that are involved in B-cell leukemia by forward genetics. ..
  13. TrkB Agonist(s), a Potential Therapy for Autism Spectrum Disorders
    Yi Eve Sun; Fiscal Year: 2010
    ..In this application, we hypothesize that activation of BDNF signaling through small molecule TrkB agonist(s) may benefit not only RTT but also other ASDs. ..
  14. Let-7 miRNA control of heart development
    Cathy J Hatcher; Fiscal Year: 2010
    ..The types of molecules being studied in this project are ideal candidate targets for such novel approaches to treat individuals with congenital heart defects. ..
  15. Cellular and Genetic Basis of Systemic Lupus
    Shu Man Fu; Fiscal Year: 2013
    ..In addition, these results have significant clinical implication in that genetic factors may allow us to tailor individual therapeutic regimens for lupus nephritis to maximize therapeutic goals and to minimize toxic side effects. ..
  16. A Novel Approach to Decoding Vertebrate Gene Regulation
    SAMANTHA JEAN RIESENFELD; Fiscal Year: 2013
    ..In addition, it will pave the way for gene therapy by genetically engineering regulatory elements that drive compounds to specific tissues at different time points. ..
  17. Do we need Y chromosome for successful reproduction?
    Monika A Ward; Fiscal Year: 2013
    ..Our results should translate to enhance treatment of human infertility associated with Y chromosome deletions. ! ..
  18. EXPRESSION OF EXOGENOUS GENES IN VECTOR MOSQUITOES
    Anthony A James; Fiscal Year: 2013
    ..stephensi to the human malaria parasite, P. falciparum. ..
  19. An.gambiae immune signaling gene SNPs and natural P. falciparum infection
    Shirley Luckhart; Fiscal Year: 2013
    ..Our studies will identify responses that are important in natural populations of An. gambiae with the long-term goal that this information can contribute to novel malaria control methods. ..
  20. Pig to human thymic xenotransplantation
    Megan Sykes; Fiscal Year: 2013
    ....
  21. TFE3 and TFEB in CD40L Dependent Murine Autoimmunity and Human Lupus
    CHRISTOPHER AJ ROMAN; Fiscal Year: 2010
    ..Such information is important to fully understand the molecular basis of this immune pathology, to devise new treatment strategies, and possibly identify new prognostic markers. ..
  22. Hydra: New Models for Aging Research
    Steven N Austad; Fiscal Year: 2013
    ..Because aging is the ultimate cause of many late life maladies, the research has the potential to not only enhance health but delay and mitigate numerous late life diseases. ..
  23. Genetic Analysis of Tbx1 in Ear Disorders
    Bernice E Morrow; Fiscal Year: 2013
    ..The goal of this project is to understand the molecular basis of inner ear defects in patients with congenital malformation disorders. ..
  24. Core Facilities for Neurobiology at Brandeis
    Michael Rosbash; Fiscal Year: 2013
    ..abstract_text> ..
  25. Molecular Regulation of an Epilepsy Modifier Gene
    BENJAMIN JORGE; Fiscal Year: 2013
    ....
  26. Development of Genetic Tools for a Short-lived Fish Model in Aging Research
    Cunming Duan; Fiscal Year: 2013
    ..A better understanding of the biology of aging regulation will likely lead to the development of diagnostic and therapeutic tools that will increase the healthy lifespan of the aging population in the United States. ..
  27. Genomic survey of cis-regulatory element function by high-throughput transgenesis
    Robert M Grainger; Fiscal Year: 2012
    ....
  28. Microbial Regulation of Host Nutrient Metabolism
    John F Rawls; Fiscal Year: 2012
    ..This new knowledge could lead to novel therapeutic approaches for prevention and treatment of obesity and related diseases. ..
  29. Functional Dissection of the Sudden Cardiac Death Associated BAZ2B locus
    Dan E Arking; Fiscal Year: 2013
    ....
  30. NF-kappaB in myeloma cell growth and survival in vivo
    Babatunde Oyajobi; Fiscal Year: 2009
    ..The research outlined will provide the basis for generation of novel therapeutic approaches to treat MM. ..
  31. Mechanisms of Pbx-directed Genetic &Transcriptional Control of Limb Development
    Licia Selleri; Fiscal Year: 2013
    ..Broadly, given the involvement of human HOX genes in leukemias and solid tumors, our studies will inform general comprehension of HOX regulation also in human neoplasia. ..
  32. The Drosophila Gene Tagging Project: Transgenes with Swappable Protein Tags
    ROGER ALLEN HOSKINS; Fiscal Year: 2013
    ..Finally, as the components of P[acman] and the tag can function in many other species, our approach is a model for other species including the mouse and human cell culture. ..
  33. EVOLUTIONARY ORIGINS OF IMMUNE-TYPE GENES
    GARY LITMAN; Fiscal Year: 2009
    ..Such information is of particular relevance to current concepts of host responses to pathogen challenge and mechanisms used to create and maintain functional polymorphism of immune receptors. ..
  34. Involvement of Nonclassical MHC in Early T Cell Ontogeny in Xenopus
    Jacques Robert; Fiscal Year: 2010
    ..For this, the investigators will use an evolutionary approach that takes advantage of the frog X. laevis, which is a unique non-mammalian comparative model that permits easy access of the thymus early during development. ..
  35. Comprehensive Identification of Worm and Fly Transcription Factor Binding Sites
    Robert H Waterston; Fiscal Year: 2012
    ..abstract_text> ..
  36. Developmental Mechanisms for the Evolution of Bone Loss
    JOHN HARVEY POSTLETHWAIT; Fiscal Year: 2012
    ..abstract_text> ..
  37. Analysis of Cis-Regulatory Mechanisms in Drosophila CNS Midline Genes
    JOSEPH CARLISLE PEARSON; Fiscal Year: 2011
    ..The Drosophila CNS midline is analogous to the vertebrate floorplate, so regulatory and signaling components may be functionally equivalent. ..
  38. Molecular and Cellular Basis for the Efficacy of Bariatric Surgery
    David H Wasserman; Fiscal Year: 2013
    ....
  39. Developing tools for genetic manipulation of hookworms
    John M Hawdon; Fiscal Year: 2013
    ..Furthermore, transgenesis would enable us to exploit the data from the imminent release of several sequenced hookworm genomes and transcriptomes for the development of novel hookworm control strategies. ..
  40. Creating Comprehensive Maps of Worm and Fly Transcription Factor Binding Sites
    Robert H Waterston; Fiscal Year: 2013
    ....
  41. Hypoxia-Inducible Factors in Liver Metabolism
    Volker H Haase; Fiscal Year: 2013
    ..The proposal has relevance for all patients with non-alcoholic fatty liver disease, obesity, diabetes and those that suffer from cardio-pulmonary conditions resulting in chronically low blood oxygen levels. ..
  42. Transposon Based Mammalian Transgenesis and Transfection
    Stefan Moisyadi; Fiscal Year: 2012
    ..Therefore, this grant should lead to improved non-viral integrating vectors for use in mammalian transgenesis and animal gene therapy experiments. ..
  43. Engineering chaperones for extracellular amyloids
    Diego E Rincon-Limas; Fiscal Year: 2013
    ....
  44. Selectin-dependent lineage-specific leukocyte recruitment in atherogenesis.
    Jonathon Homeister; Fiscal Year: 2012
    ....
  45. Characterization of the First HSCs During Mouse Ontogeny
    Elaine A Dzierzak; Fiscal Year: 2013
    ..If indeed embryonic aorta-derived HSCs migrate and colonize the adult bone marrow, our insights into their generation and expansion should lead to novel methods for clinical HSC expansion and thus, improve transplantation therapies. ..
  46. Zinc finger nuclease induced knockout and knock-in models in zebrafish
    Meera T Saxena; Fiscal Year: 2011
    ....
  47. ABCG1 and endothelial function
    ALAN RICHARD TALL; Fiscal Year: 2013
    ..These studies will use novel animal and cellular models to provide new insights into the mechanisms of athero-protective effects of HDL involving arterial endothelium. ..
  48. Role of TGF beta in Airway Hyperresponsiveness in Vivo
    Blanca Camoretti-Mercado; Fiscal Year: 2012
    ..They will also be the foundation for building a high-quality translational research program and securing independent federal funding. (End of Abstract) ..
  49. Plasticity of intact circuits restores function after a spinal cord injury.
    WILLIAM BEN CAFFERTY; Fiscal Year: 2012
    ..abstract_text> ..
  50. Genomics Resources and Infrastucture for the Zebrafish
    Chris T Amemiya; Fiscal Year: 2012
    ..In addition in keeping with the educational mission of NCRR, science outreach will be established for undergraduates and science teachers through partnerships with local educational and science outreach programs. ..
  51. Fragile X pre-mutation and ovarian insufficiency
    Katherine F Roby; Fiscal Year: 2013
    ..With the completion of these studies we will have both global and targeted premutation expansion mouse models specifically suited to explore the mechanisms whereby FMR1 premutation impacts the reproductive system in women. ..
  52. Therapeutic Targeting of Wnt Signaling
    Dianqing Wu; Fiscal Year: 2012
    ..2) To further characterize the Wnt antagonistic compounds and to refine and expand the virtual screen. ..
  53. Introducing restriction factors into the genome of an AIDS virus host species
    Eric M Poeschla; Fiscal Year: 2013
    ....
  54. Oncogene susceptibility: physiological state &breast cell differentiation
    Yi Li; Fiscal Year: 2013
    ....
  55. Transposon-based screens for colorectal cancer genes
    DAVID ANDREW LARGAESPADA; Fiscal Year: 2013
    ..We will discover what genes, when damaged, can cause these tumors. This will help us decide how best to treat this very common and often lethal disease. ..
  56. B Cells and Type 1 Diabetes
    John C Cambier; Fiscal Year: 2013
    ..The experiments will address the overarching hypothesis that in Type 1 Diabetes the silence of high affinity insulin-specific B cells is broken and these cells promote disease by presentation of autoantigen to CD4 T cells. ..
  57. Request for support for the Second International Symposium: Facing the Challenges
    ALEXANDER SIMEON RAIKHEL; Fiscal Year: 2012
    ..The symposium strives to engage senior faculty with junior faculty and students in order to ensure that new and sustainable solutions to the global health problems caused by these vectors can be found. ..
  58. Generation of an In Vivo Human Genome Enhancer Dataset
    LEN ALEXANDER PENNACCHIO; Fiscal Year: 2013
    ..The identification of positive signatures of enhancers in vivo is expected to significantly fill our void in gene regulatory annotation of the human genome and to decipher their mutation as a cause of human disease. ..
  59. Gene networks regulating sex determination in vertebrates
    Thomas D Kocher; Fiscal Year: 2011
    ..This knowledge will contribute to the discovery of new therapies for these defects in humans. ..
  60. GENE EXPRESSION IN NORMAL AND CATARACTOUS LENS
    Suraj P Bhat; Fiscal Year: 2010
    ....
  61. Transgenesis in songbirds for the genetic manipulation of neuronal circuits
    Carlos Lois; Fiscal Year: 2013
    ..We propose to develop new molecular tools that will allow for genetic manipulation of songbirds to generate animal models of human diseases that affect complex cognitive functions and communication disorders. ..
  62. Thyroidal Macrophages in Autoimmune Hypothyroidism and Hurthle Cells
    Patrizio Caturegli; Fiscal Year: 2010
    ..The present proposal mainly aims to characterize the role of LMP2 and macrophages in autoimmune thyroiditis. ..
  63. GFP Reporters for the chondrocyte lineage
    David Rowe; Fiscal Year: 2009
    ..The GFP tool set that this grant will produce will be the first step in a more knowledge based approach to regenerative medicine for diseases of the joint. ..
  64. FRACTIONATED HYPERTHERMIA AND HEAT SHOCK PROTEINS
    Gloria Li; Fiscal Year: 1999
    ..Results from this study will assist us in understanding the functions of HSF1 and CHBF, and their involvement in the dual control mechanism of heat shock gene expression. ..
  65. Do estrogen receptors in B cells and DC mediate sex bias in murine lupus?
    Susan Kovats; Fiscal Year: 2009
    ..This knowledge will help to understand why autoimmune diseases preferentially afflict women. ..
  66. Melanopsin-expressing retinal ganglion cells: novel genetic tools
    Paulo Kofuji; Fiscal Year: 2009
    ..Determining how the intrinsically photosensitive ganglion cells work may allow the treatment of disorders such as sleep disorders and seasonal depression. ..
  67. STRATEGIES FOR PRIMATE TRANSGENESIS
    Thaddeus Golos; Fiscal Year: 2003
    ..abstract_text> ..
  68. Craniofacial defects in ethanol-exposed zebrafish
    Sara Ahlgren; Fiscal Year: 2004
    ..These experiments will lay the groundwork to expand our understanding of the mechanisms of craniofacial defects following embryonic exposure to alcohol. ..
  69. Transgenesis-Ready Mice with Tn5 Transposase
    JOANNE EBESU; Fiscal Year: 2007
    ..Thus, this research fits with NIH's goals to advance the understanding of basic biological systems, improve the control of disease, and enhance health. [unreadable] [unreadable] [unreadable]..
  70. Structure & function of cardiac contractile proteins
    Jeffrey Robbins; Fiscal Year: 2004
    ..Together with the models above, it will provide a comprehensive picture of the alpha-MHC's effects on the development of hypertrophy, dilation and failure. ..
  71. Avian transgenesis via site-directed integration
    ALEX HARVEY; Fiscal Year: 2004
    ..This novel technology will expedite the creation of poultry that can produce pharmaceuticals, thereby facilitating drug development, enhancing clinical trials and lowering the cost of pharmaceuticals. ..
  72. FAMILIAL PATENT DUCTUS ARTERIOSUS
    Bruce Gelb; Fiscal Year: 2004
    ..Aside from illuminating one pathway toward the clinical endpoint of PDA, it will provide the starting place for identifying genes critical to ductal development that are activated by Char syndrome-related genes. ..