gene targeting

Summary

Summary: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination.

Top Publications

  1. pmc A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity
    Claudio Mussolino
    Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany
    Nucleic Acids Res 39:9283-93. 2011
  2. ncbi Heterologous modules for efficient and versatile PCR-based gene targeting in Schizosaccharomyces pombe
    J Bahler
    Department of Biology, University of North Carolina, Chapel Hill 27599 3280, USA
    Yeast 14:943-51. 1998
  3. pmc Targeting DNA double-strand breaks with TAL effector nucleases
    Michelle Christian
    Department of Plant Pathology, Iowa State University, Ames, Iowa 50011, USA
    Genetics 186:757-61. 2010
  4. pmc Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases
    Dirk Hockemeyer
    The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA
    Nat Biotechnol 27:851-7. 2009
  5. ncbi Generalized lacZ expression with the ROSA26 Cre reporter strain
    P Soriano
    Nat Genet 21:70-1. 1999
  6. pmc Targeted genome editing across species using ZFNs and TALENs
    Andrew J Wood
    Howard Hughes Medical Institute HHMI, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 3204, USA
    Science 333:307. 2011
  7. ncbi Highly efficient endogenous human gene correction using designed zinc-finger nucleases
    Fyodor D Urnov
    Sangamo BioSciences, Inc, Pt Richmond Tech Center 501, Canal Blvd, Suite A100 Richmond, California 94804, USA
    Nature 435:646-51. 2005
  8. ncbi An unbiased genome-wide analysis of zinc-finger nuclease specificity
    Richard Gabriel
    Department of Translational Oncology, National Center for Tumor Diseases NCT and German Cancer Research Center DKFZ, Heidelberg, Germany
    Nat Biotechnol 29:816-23. 2011
  9. pmc Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes
    Ting Li
    Department of Genetics, Development and Cell Biology, Laurence H Baker Center for Bioinformatics and Biological Statistics, University of Nebraska, Lincoln, NE 68588, USA
    Nucleic Acids Res 39:6315-25. 2011
  10. pmc Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases
    Yannick Doyon
    Sangamo BioSciences, Inc, Pt Richmond Tech Center, 501 Canal Blvd, Suite A100, Richmond, California 94804, USA
    Nat Biotechnol 26:702-8. 2008

Research Grants

  1. Small Molecule targeting of NADPH oxidase in neutrophils
    Marie Dominique Filippi; Fiscal Year: 2010
  2. Lipid Droplet Metabolism
    Fredric B Kraemer; Fiscal Year: 2013
  3. P38 MAP KINASE SIGNALING IN SKIN
    Tatiana Efimova; Fiscal Year: 2013
  4. DNA Damage Checkpoint and Cancer
    Toru Ouchi; Fiscal Year: 2012
  5. Development of a Porcine Model of Atherosclerosis
    Christopher Rogers; Fiscal Year: 2010
  6. CELLULAR REGULATION OF CLATHRIN ASSEMBLY AND FUNCTION
    Frances M Brodsky; Fiscal Year: 2013
  7. Role of estrogen-related receptors in cardiac and skeletal muscle
    Janice M Huss; Fiscal Year: 2010
  8. The Role of CD5 in B-Cell Development and Autoimmunity
    Chander Raman; Fiscal Year: 2012
  9. Role of Heat Shock Transcription Factor Hsf1 in Tumorigenesis
    Nahid F Mivechi; Fiscal Year: 2013
  10. Development of a Porcine Model of Ataxia-Telangiectasia
    Christopher Rogers; Fiscal Year: 2011

Detail Information

Publications365 found, 100 shown here

  1. pmc A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity
    Claudio Mussolino
    Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany
    Nucleic Acids Res 39:9283-93. 2011
    ..The combination of high nuclease activity with reduced cytotoxicity and the simple design process marks TALENs as a key technology platform for targeted modifications of complex genomes...
  2. ncbi Heterologous modules for efficient and versatile PCR-based gene targeting in Schizosaccharomyces pombe
    J Bahler
    Department of Biology, University of North Carolina, Chapel Hill 27599 3280, USA
    Yeast 14:943-51. 1998
    ..In most cases, the efficiency of homologous integration was > or = 50%, and the lowest efficiency encountered was 17%. The methodology and constructs described here should greatly facilitate analysis of gene function in S. pombe...
  3. pmc Targeting DNA double-strand breaks with TAL effector nucleases
    Michelle Christian
    Department of Plant Pathology, Iowa State University, Ames, Iowa 50011, USA
    Genetics 186:757-61. 2010
    ..Both native and custom TALE-nuclease fusions direct DNA double-strand breaks to specific, targeted sites...
  4. pmc Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases
    Dirk Hockemeyer
    The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA
    Nat Biotechnol 27:851-7. 2009
    ..cell type-specific lineage reporters, as well as reliable tools to disrupt, repair or overexpress genes by gene targeting, are inefficient at best and thus are not routinely used...
  5. ncbi Generalized lacZ expression with the ROSA26 Cre reporter strain
    P Soriano
    Nat Genet 21:70-1. 1999
  6. pmc Targeted genome editing across species using ZFNs and TALENs
    Andrew J Wood
    Howard Hughes Medical Institute HHMI, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 3204, USA
    Science 333:307. 2011
    ....
  7. ncbi Highly efficient endogenous human gene correction using designed zinc-finger nucleases
    Fyodor D Urnov
    Sangamo BioSciences, Inc, Pt Richmond Tech Center 501, Canal Blvd, Suite A100 Richmond, California 94804, USA
    Nature 435:646-51. 2005
    ..We observe comparably high frequencies in human T cells, raising the possibility of strategies based on zinc-finger nucleases for the treatment of disease...
  8. ncbi An unbiased genome-wide analysis of zinc-finger nuclease specificity
    Richard Gabriel
    Department of Translational Oncology, National Center for Tumor Diseases NCT and German Cancer Research Center DKFZ, Heidelberg, Germany
    Nat Biotechnol 29:816-23. 2011
    ..Comprehensive mapping of ZFN activity in vivo will facilitate the broad application of these reagents in translational research...
  9. pmc Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes
    Ting Li
    Department of Genetics, Development and Cell Biology, Laurence H Baker Center for Bioinformatics and Biological Statistics, University of Nebraska, Lincoln, NE 68588, USA
    Nucleic Acids Res 39:6315-25. 2011
    ....
  10. pmc Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases
    Yannick Doyon
    Sangamo BioSciences, Inc, Pt Richmond Tech Center, 501 Canal Blvd, Suite A100, Richmond, California 94804, USA
    Nat Biotechnol 26:702-8. 2008
    ..The frequency and precision of gene-disruption events observed suggest that this approach should be applicable to any loci in zebrafish or in other organisms that allow mRNA delivery into the fertilized egg...
  11. pmc Genome engineering with zinc-finger nucleases
    Dana Carroll
    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah 84112 5650, USA
    Genetics 188:773-82. 2011
    ..The bright prospects for future applications of ZFNs, including human gene therapy, are discussed...
  12. ncbi Conditional gene targeting in macrophages and granulocytes using LysMcre mice
    B E Clausen
    Institute for Genetics, University of Cologne, Germany
    Transgenic Res 8:265-77. 1999
    Conditional mutagenesis in mice has recently been made possible through the combination of gene targeting techniques and site-directed mutagenesis, using the bacteriophage P1-derived Cre/loxP recombination system...
  13. pmc Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases
    Xiangdong Meng
    Program in Gene Function and Expression, University of Massachusetts Medical School, Lazare Research Building, 6th Floor, 364 Plantation St, Worcester, Massachusetts 01605, USA
    Nat Biotechnol 26:695-701. 2008
    ..The use of engineered ZFNs to introduce heritable mutations into a genome obviates the need for embryonic stem cell lines and should be applicable to most animal species for which early-stage embryos are easily accessible...
  14. ncbi Inducible gene targeting in mice
    R Kuhn
    Institute for Genetics, University of Cologne, Germany
    Science 269:1427-9. 1995
    A method of gene targeting that allows the inducible inactivation of a target gene in mice is presented. The method uses an interferon-responsive promoter to control the expression of Cre recombinase...
  15. ncbi Fusion PCR and gene targeting in Aspergillus nidulans
    Edyta Szewczyk
    Department of Molecular Genetics, Ohio State University, 484 West 12th Avenue, Columbus, Ohio 43210, USA
    Nat Protoc 1:3111-20. 2006
    ..nidulans with fusion PCR products results in high frequencies of accurate gene targeting. Fusion PCR takes less than 2 d. Protoplast formation and transformation takes less than 1 d.
  16. pmc An optimized two-finger archive for ZFN-mediated gene targeting
    Ankit Gupta
    Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, USA
    Nat Methods 9:588-90. 2012
    ..Using this archive, we introduced lesions at 9 of 11 target sites in the zebrafish genome...
  17. pmc Gene targeting of a disease-related gene in human induced pluripotent stem and embryonic stem cells
    Jizhong Zou
    Stem Cell Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell Stem Cell 5:97-110. 2009
    We report here homologous recombination (HR)-mediated gene targeting of two different genes in human iPS cells (hiPSCs) and human ES cells (hESCs)...
  18. pmc In situ genetic correction of the sickle cell anemia mutation in human induced pluripotent stem cells using engineered zinc finger nucleases
    Vittorio Sebastiano
    Department of Pathology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford California, USA
    Stem Cells 29:1717-26. 2011
    ..However, gene targeting in human pluripotent cells has remained challenging and inefficient...
  19. pmc In vivo genome editing restores haemostasis in a mouse model of haemophilia
    Hojun Li
    Division of Hematology, CTRB 5000, Children s Hospital of Philadelphia, 3501 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA
    Nature 475:217-21. 2011
    ..The level of gene targeting achieved was sufficient to correct the prolonged clotting times in a mouse model of haemophilia B, and ..
  20. ncbi Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos
    Yuyu Niu
    Yunnan Key Laboratory of Primate Biomedical Research, Kunming 650500, China Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming 650500, China
    Cell 156:836-43. 2014
    ..By coinjection of Cas9 mRNA and sgRNAs into one-cell-stage embryos, we successfully achieve precise gene targeting in cynomolgus monkeys...
  21. pmc Efficient gene targeting by TAL effector nucleases coinjected with exonucleases in zygotes
    Tomoji Mashimo
    Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    Sci Rep 3:1253. 2013
    ..These findings demonstrate TALENs with Exo1 is an easy and efficient method of generating gene knockouts using zygotes, which increases the range of gene targeting technologies available to various species.
  22. pmc Rapid "open-source" engineering of customized zinc-finger nucleases for highly efficient gene modification
    Morgan L Maeder
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Mol Cell 31:294-301. 2008
    ..In summary, OPEN provides an "open-source" method for rapidly engineering highly active zinc-finger arrays, thereby enabling broader practice, development, and application of ZFN technology for biological research and gene therapy...
  23. ncbi Enhancing gene targeting with designed zinc finger nucleases
    Marina Bibikova
    Department of Biochemistry, University of Utah School of Medicine, 20 North 1900 East, Salt Lake City, UT 84132 3201, USA
    Science 300:764. 2003
  24. pmc High-efficiency and heritable gene targeting in mouse by transcription activator-like effector nucleases
    Zhongwei Qiu
    Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China
    Nucleic Acids Res 41:e120. 2013
    ..Together, our results suggest that TALENs are an effective genetic tool for rapid gene disruption with high efficiency and heritability in mouse with distinct genetic background...
  25. ncbi Targeted integration in rat and mouse embryos with zinc-finger nucleases
    Xiaoxia Cui
    Sigma Advanced Genetic Engineering Labs, Sigma Aldrich Biotechnology, St Louis, Missouri, USA
    Nat Biotechnol 29:64-7. 2011
    b>Gene targeting is indispensible for reverse genetics and the generation of animal models of disease...
  26. pmc Targeted chromosomal deletions in human cells using zinc finger nucleases
    Hyung Joo Lee
    Department of Chemistry, Seoul National University, Seoul, South Korea
    Genome Res 20:81-9. 2010
    ..Thus, ZFN-induced genomic deletions should be broadly useful as a novel method in biomedical research, biotechnology, and gene therapy...
  27. pmc Targeted genome modification in mice using zinc-finger nucleases
    Iara D Carbery
    Sigma Advanced Genetic Engineering Labs, Sigma Aldrich Biotechnology, St Louis, MO 63146, USA
    Genetics 186:451-9. 2010
    Homologous recombination-based gene targeting using Mus musculus embryonic stem cells has greatly impacted biomedical research...
  28. pmc Targeted chromosomal duplications and inversions in the human genome using zinc finger nucleases
    Hyung Joo Lee
    National Creative Research Initiatives Center for Genome Engineering, Department of Chemistry, Seoul National University, 599 Gwanak Ro, Seoul, South Korea
    Genome Res 22:539-48. 2012
    ..In addition, our method raises the possibility of correcting genetic defects caused by chromosomal rearrangements and holds new promise in gene and cell therapy...
  29. pmc Highly improved gene targeting by germline-specific Cas9 expression in Drosophila
    Shu Kondo
    Invertebrate Genetics Laboratory, National Institute of Genetics and Department of Genetics, The Graduate University for Advanced Studies, Mishima, Shizuoka 411 8540, Japan
    Genetics 195:715-21. 2013
    We report a simple yet extremely efficient platform for systematic gene targeting by the RNA-guided endonuclease Cas9 in Drosophila...
  30. pmc Homing endonucleases: from microbial genetic invaders to reagents for targeted DNA modification
    Barry L Stoddard
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, A3 025, Seattle, WA 98109, USA
    Structure 19:7-15. 2011
    ..Engineered homing endonucleases proteins are now being used to generate targeted genomic modifications for a variety of biotech and medical applications...
  31. ncbi Chimeric nucleases stimulate gene targeting in human cells
    Matthew H Porteus
    Department of Biology, California Institute of Technology, Pasadena CA 91125, USA
    Science 300:763. 2003
  32. pmc Requirement of bic/microRNA-155 for normal immune function
    Antony Rodriguez
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
    Science 316:608-11. 2007
    ..Our work suggests that bic/microRNA-155 plays a key role in the homeostasis and function of the immune system...
  33. ncbi Zinc-finger nucleases: the next generation emerges
    Toni Cathomen
    Institute of Virology CBF, Charite Medical School, Berlin, Germany
    Mol Ther 16:1200-7. 2008
    ..One particularly promising technology is based on the homologous recombination (HR) pathway and is known as gene targeting. Until recently, the low frequency of HR in mammalian cells, and the resulting dependence on selection to ..
  34. ncbi Mobile group II introns
    Alan M Lambowitz
    Institute for Cellular and Molecular Biology, Department of Chemistry and Biochemistry, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Texas 78712, USA
    Annu Rev Genet 38:1-35. 2004
    ..Finally, we describe the development of mobile group II introns into gene-targeting vectors, "targetrons," which have programmable target specificity...
  35. pmc The magical touch: genome targeting in epidermal stem cells induced by tamoxifen application to mouse skin
    V Vasioukhin
    Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 96:8551-6. 1999
    ..These tools now pave the way for testing the functional role of different somatic mutations that may exist in mosaic disorders of the skin, including squamous and basal cell carcinomas...
  36. ncbi Gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century
    Mario R Capecchi
    Howard Hughes Medical Institute, Department of Human Genetics, University of Utah School of Medicine, 15 North 2030 East, Room 5100, Salt Lake City, Utah 84112 5331, USA
    Nat Rev Genet 6:507-12. 2005
    b>Gene targeting in mouse embryonic stem cells has become the 'gold standard' for determining gene function in mammals. Since its inception, this technology has revolutionized the study of mammalian biology and human medicine...
  37. pmc Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus
    S Srinivas
    Department of Genetics and Development, Columbia University, New York, USA
    BMC Dev Biol 1:4. 2001
    ....
  38. pmc Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells
    A J Pierce
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, and Cornell University Graduate School of Medical Sciences, New York, New York 10021, USA
    Genes Dev 15:3237-42. 2001
    ..Neither sister-chromatid exchange nor gene-targeting frequencies show a dependence on these NHEJ proteins. A Ku-modulated two-ended versus one-ended chromosome break model is presented to explain these results...
  39. pmc High-frequency modification of plant genes using engineered zinc-finger nucleases
    Jeffrey A Townsend
    Department of Genetics, Development and Cell Biology, Iowa State University, Ames, Iowa 50011, USA
    Nature 459:442-5. 2009
    An efficient method for making directed DNA sequence modifications to plant genes (gene targeting) is at present lacking, thereby frustrating efforts to dissect plant gene function and engineer crop plants that better meet the world's ..
  40. pmc Gene targeting to the ROSA26 locus directed by engineered zinc finger nucleases
    Pablo Perez-Pinera
    Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA
    Nucleic Acids Res 40:3741-52. 2012
    ..For example, gene targeting to the ROSA26 locus by homologous recombination in embryonic stem cells is commonly used for mouse ..
  41. pmc Engineering of human pluripotent stem cells by AAV-mediated gene targeting
    Iram F Khan
    Department of Medicine, University of Washington, Seattle, Washington 98195, USA
    Mol Ther 18:1192-9. 2010
    ..Here, we show that adeno-associated virus (AAV) gene targeting vectors can be used to genetically engineer human embryonic stem cells (ESCs) and induced pluripotent stem ..
  42. pmc Gene targeting by homologous recombination in mouse zygotes mediated by zinc-finger nucleases
    Melanie Meyer
    Institute for Developmental Genetics, Helmholtz Center Munich, Munich, Germany
    Proc Natl Acad Sci U S A 107:15022-6. 2010
    b>Gene targeting by homologous recombination in embryonic stem cells is extensively used to generate specific mouse mutants. However, most mammalian species lack tools for targeted gene manipulation...
  43. ncbi Late embryonic lethality and impaired V(D)J recombination in mice lacking DNA ligase IV
    K M Frank
    The Children s Hospital, Department of Genetics, Harvard University Medical School, Boston, Massachusetts 02115, USA
    Nature 396:173-7. 1998
    ..However, Ku-deficient mice are viable, so ligase IV must also be required for processes and/or in cell types in which Ku is dispensable...
  44. pmc Evaluation and application of modularly assembled zinc-finger nucleases in zebrafish
    Cong Zhu
    Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Development 138:4555-64. 2011
    ..This work provides a resource to allow targeted germline gene inactivation in zebrafish and highlights the benefit of a definitive reverse genetic strategy to reveal gene function...
  45. pmc Efficient gene targeting in Drosophila by direct embryo injection with zinc-finger nucleases
    Kelly J Beumer
    Department of Biochemistry, University of Utah School of Medicine, 15 North Medical Drive East, Salt Lake City, UT 84112 5650, USA
    Proc Natl Acad Sci U S A 105:19821-6. 2008
    We report very high gene targeting frequencies in Drosophila by direct embryo injection of mRNAs encoding specific zinc-finger nucleases (ZFNs)...
  46. pmc Defective resection at DNA double-strand breaks leads to de novo telomere formation and enhances gene targeting
    Woo Hyun Chung
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America
    PLoS Genet 6:e1000948. 2010
    ..In contrast to this decreased and alternative DSB repair, the efficiency and accuracy of gene targeting increases dramatically in sgs1Delta exo1Delta cells, suggesting that transformed DNA is very stable in these ..
  47. ncbi Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning
    Liangxue Lai
    Department of Animal Science, University of Missouri, Columbia, MO 65211, USA
    Science 295:1089-92. 2002
    ..These pigs were produced by nuclear transfer technology; clonal fetal fibroblast cell lines were used as nuclear donors for embryos reconstructed with enucleated pig oocytes...
  48. pmc From the Cover: Directed, efficient, and versatile modifications of the Drosophila genome by genomic engineering
    Juan Huang
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Proc Natl Acad Sci U S A 106:8284-9. 2009
    ..Genomic engineering is a 2-step process that combines the ends-out (replacement) gene targeting with phage integrase phiC31-mediated DNA integration...
  49. ncbi Expression profiling reveals off-target gene regulation by RNAi
    Aimee L Jackson
    Rosetta Inpharmatics LLC, 12040 115th Avenue NE, Kirkland, Washington 98034, USA
    Nat Biotechnol 21:635-7. 2003
    ..These results demonstrate that siRNAs may cross-react with targets of limited sequence similarity...
  50. ncbi High-throughput engineering of the mouse genome coupled with high-resolution expression analysis
    David M Valenzuela
    Regeneron Pharmaceuticals, Inc, 777 Old Saw Mill Road, Tarrytown, New York 10591, USA
    Nat Biotechnol 21:652-9. 2003
    ..5-1.0% of the entire genome. We also provide dozens of informative expression patterns involving cells in the nervous system, immune system, vasculature, skeleton, fat and other tissues...
  51. ncbi Functional organization of the yeast proteome by systematic analysis of protein complexes
    Anne Claude Gavin
    Cellzome AG, Meyerhofstrasse 1, 69117 Heidelberg, Germany
    Nature 415:141-7. 2002
    ..This higher-order map contains fundamental biological information and offers the context for a more reasoned and informed approach to drug discovery...
  52. pmc Agouti C57BL/6N embryonic stem cells for mouse genetic resources
    Stephen J Pettitt
    Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK
    Nat Methods 6:493-5. 2009
    ..These cells provide a robust foundation for large-scale mouse knockout programs that aim to provide a public resource of targeted mutations in the C57BL/6 genetic background...
  53. pmc Rapid and cost-effective gene targeting in rat embryonic stem cells by TALENs
    Chang Tong
    Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
    J Genet Genomics 39:275-80. 2012
    ..Genetic manipulation in rats has lagged behind that in mice due to the lack of efficient gene targeting tools...
  54. ncbi Gene targeting by homologous recombination in Drosophila
    Y S Rong
    Department of Biology, University of Utah, Salt Lake City, UT 84112, USA
    Science 288:2013-8. 2000
    ..A method is described that enables analogous manipulations of the Drosophila genome. This technique may also be applicable to other organisms for which gene-targeting procedures do not yet exist...
  55. pmc Conditional gene targeting in mouse pancreatic ß-Cells: analysis of ectopic Cre transgene expression in the brain
    Barton Wicksteed
    Section of Adult and Pediatric Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Chicago, Chicago, llinois, USA
    Diabetes 59:3090-8. 2010
    Conditional gene targeting has been extensively used for in vivo analysis of gene function in β-cell biology...
  56. ncbi c-Myc regulates mammalian body size by controlling cell number but not cell size
    A Trumpp
    Swiss Institute for Experimental Cancer Research ISREC, Ch des Boveresses 155, CH 1066 Epalinges, Switzerland
    Nature 414:768-73. 2001
    ..We propose that in mammals c-Myc controls the decision to divide or not to divide and thereby functions as a crucial mediator of signals that determine organ and body size...
  57. ncbi Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice
    D E Cressman
    Department of Genetics and Medicine, University of Pennsylvania School of Medicine, 705a Stellar Chance, 422 Curie Boulevard, Philadelphia, PA 19104 6145, USA
    Science 274:1379-83. 1996
    ....
  58. pmc A TALE of two nucleases: gene targeting for the masses?
    Karl J Clark
    Department of Biochemistry and Molecular Biology, Mayo Addiction Research Center, Mayo Clinic, Rochester, Minnesota 55905, USA
    Zebrafish 8:147-9. 2011
    ..TALEN construction is simpler, potentially more reliable, and in the few cases examined, shows fewer off-target effects than corresponding ZFNs. TALENs promise to bring gene targeting to the majority of zebrafish laboratories.
  59. pmc The colorectal microRNAome
    Jordan M Cummins
    The Sidney Kimmel Comprehensive Cancer Center and Howard Hughes Medical Institute, Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA
    Proc Natl Acad Sci U S A 103:3687-92. 2006
    ..These studies suggest that the human genome contains many more miRNAs than currently identified and provide an approach for the large-scale experimental cloning of novel human miRNAs in human tissues...
  60. ncbi HIV-1 integration in the human genome favors active genes and local hotspots
    Astrid R W Schroder
    Infectious Disease Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell 110:521-9. 2002
    ..4 kb region containing 1% of sites. These data document unexpectedly strong biases in integration site selection and suggest how selective targeting promotes aggressive HIV replication...
  61. ncbi Vagaries of conditional gene targeting
    Marc Schmidt-Supprian
    Department of Pathology, Harvard Medical School and the CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA
    Nat Immunol 8:665-8. 2007
  62. pmc High frequency targeted mutagenesis in Arabidopsis thaliana using zinc finger nucleases
    Feng Zhang
    Department of Genetics, Cell Biology, and Development and Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA
    Proc Natl Acad Sci U S A 107:12028-33. 2010
    ..Taken together, our results suggest that it should now be possible to obtain mutations in any Arabidopsis target gene regardless of its mutant phenotype...
  63. pmc Targeted gene addition into a specified location in the human genome using designed zinc finger nucleases
    Erica A Moehle
    Sangamo BioSciences, Inc, Point Richmond Technology Center, 501 Canal Boulevard, Suite A100, Richmond, CA 94804, USA
    Proc Natl Acad Sci U S A 104:3055-60. 2007
    ....
  64. ncbi Efficient gene targeting in the moss Physcomitrella patens
    D G Schaefer
    Laboratoire de Phytogénétique Cellulaire, Universite de Lausanne, Lausanne Dorigny, Switzerland
    Plant J 11:1195-206. 1997
    ..experiments designed to target three single-copy genomic loci were performed to determine the efficiency of gene targeting in this plant...
  65. pmc Testing gene function early in the B cell lineage in mb1-cre mice
    E Hobeika
    Max Planck Institute of Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany
    Proc Natl Acad Sci U S A 103:13789-94. 2006
    ..The availability of a mouse line with efficient cre-mediated recombination at an early developmental stage in the B lineage provides an opportunity to study the role of various genes specifically in B cell development and function...
  66. pmc Tapping natural reservoirs of homing endonucleases for targeted gene modification
    Ryo Takeuchi
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North A3 025, Seattle, WA 98109, USA
    Proc Natl Acad Sci U S A 108:13077-82. 2011
    ..The ubiquitous presence and diversity of LHEs described in this study may facilitate the creation of many tailored nucleases for genome editing...
  67. pmc High efficiency site-specific genetic engineering of the mosquito genome
    D D Nimmo
    Centre for Applied Entomology and Parasitology, Keele University, Keele, Staffordshire UK
    Insect Mol Biol 15:129-36. 2006
    ..9-fold. The ability to efficiently target transgenes to specific chromosomal locations and the potential to integrate very large transgenes has broad applicability to research on many medically and economically important species...
  68. pmc Structure-guided reprogramming of serine recombinase DNA sequence specificity
    Thomas Gaj
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 108:498-503. 2011
    ..These results demonstrate that unique resolvase and invertase derivatives can be developed to site-specifically modify the human genome in the context of zinc-finger recombinase fusion proteins...
  69. pmc Efficient targeting of a SCID gene by an engineered single-chain homing endonuclease
    Sylvestre Grizot
    Cellectis SA, Cellectis Genome Surgery, 93235 Romainville, France
    Nucleic Acids Res 37:5405-19. 2009
    ..These properties rank this new generation of endonucleases among the best molecular scissors available for genome surgery strategies, potentially avoiding the deleterious effects of previous gene therapy approaches...
  70. ncbi The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells
    Kaoru Mitsui
    Laboratory of Animal Molecular Technology, Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Nara 630 0192, Japan
    Cell 113:631-42. 2003
    ..nanog-deficient ES cells lost pluripotency and differentiated into extraembryonic endoderm lineage. These data demonstrate that Nanog is a critical factor underlying pluripotency in both ICM and ES cells...
  71. ncbi Meganucleases and DNA double-strand break-induced recombination: perspectives for gene therapy
    Frédéric Pâques
    Cellectis SA, 102, route de Noisy, 93 340 Romainville Cedex France
    Curr Gene Ther 7:49-66. 2007
    ..large (>12 bp) sequence sites and several laboratories have used these proteins to induce highly efficient gene targeting in mammalian cells...
  72. pmc Expanding or restricting the target site repertoire of zinc-finger nucleases: the inter-domain linker as a major determinant of target site selectivity
    Eva Maria Händel
    Charite Medical School, Institute of Virology CBF, Berlin, Germany
    Mol Ther 17:104-11. 2009
    ..We achieved gene targeting in up to 20% of transfected cells and identified linker variants that enforce DNA cleavage at narrowly defined ..
  73. pmc The mechanism of gene targeting in Physcomitrella patens: homologous recombination, concatenation and multiple integration
    Yasuko Kamisugi
    Centre for Plant Sciences, Faculty of Biological Sciences, Leeds University, Leeds LS2 9JT, UK
    Nucleic Acids Res 34:6205-14. 2006
    The model bryophyte Physcomitrella patens exhibits high frequencies of gene targeting when transformed with DNA constructs containing sequences homologous with genomic loci...
  74. pmc Modeling disease mutations by gene targeting in one-cell mouse embryos
    Melanie Meyer
    Institute for Developmental Genetics, Helmholtz Center Munich, 85764 Munich, Germany
    Proc Natl Acad Sci U S A 109:9354-9. 2012
    b>Gene targeting by zinc-finger nucleases in one-cell embryos provides an expedite mutagenesis approach in mice, rats, and rabbits...
  75. pmc Evaluation of OPEN zinc finger nucleases for direct gene targeting of the ROSA26 locus in mouse embryos
    Mario Hermann
    Institute of Laboratory Animal Science, University of Zurich, Zurich, Switzerland
    PLoS ONE 7:e41796. 2012
    ..Commercial ZFNs were reported to enhance gene targeting directly in mouse zygotes, whereas similar approaches using publicly available resources have not yet been ..
  76. pmc Gene targeting reveals a widespread role for the high-mobility-group transcription factor Sox11 in tissue remodeling
    Elisabeth Sock
    Institut fur Biochemie, Universitat Erlangen Nurnberg, Fahrstrasse 17, D 91054 Erlangen, Germany
    Mol Cell Biol 24:6635-44. 2004
    ..This phenotype suggests a prime function for Sox11 in tissue remodeling and identifies SOX11 as a potentially mutated gene in corresponding human malformation syndromes...
  77. ncbi Reverse genetic approaches in zebrafish
    Peng Huang
    Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing, China
    J Genet Genomics 39:421-33. 2012
    ..genetic approaches for loss-of-function studies used and emerging in zebrafish, including strategies based on genome-wide mutagenesis and methods for site-specific gene targeting. Future directions and expectations will also be discussed.
  78. pmc Targeted plasmid integration into the human genome by an engineered zinc-finger recombinase
    Charles A Gersbach
    The Skaggs Institute for Chemical Biology, Department of Molecular Biology, CA, USA
    Nucleic Acids Res 39:7868-78. 2011
    ..This work demonstrates the potential for broad applicability of the ZFR technology in genome engineering, synthetic biology and gene therapy...
  79. pmc Efficient ends-out gene targeting in Drosophila
    Juan Huang
    Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennyslvania 15261, USA
    Genetics 180:703-7. 2008
    ..we describe several approaches to improve the scalability and throughput of major genetic crosses in ends-out gene targeting. We generated new sets of targeting vectors and fly stocks and introduced a novel negative selection marker ..
  80. pmc Targeting individual subunits of the FokI restriction endonuclease to specific DNA strands
    Kelly L Sanders
    Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol, UK
    Nucleic Acids Res 37:2105-15. 2009
    ..The latter extends the range of enzymes for nicking specified strands at specific sequences, and may facilitate further applications of FokI in gene targeting.
  81. ncbi Disruption of mouse RAD54 reduces ionizing radiation resistance and homologous recombination
    J Essers
    Medical Genetics Center, Department of Cell Biology and Genetics, Erasmus University Rotterdam, The Netherlands
    Cell 89:195-204. 1997
    ..b>Gene targeting experiments demonstrate that homologous recombination in mRAD54-/- cells is reduced compared to wild-type ..
  82. ncbi Gene targeting in human pluripotent stem cells with adeno-associated virus vectors
    Kaoru Mitsui
    Gene Therapy Division, Research Center for Genomic Medicine, Saitama Medical University, 1397 1 Yamane, Hidaka, Saitama 350 1241, Japan
    Biochem Biophys Res Commun 388:711-7. 2009
    ..To make full use of hESCs or hiPSCs for both basic and clinical research, genetic modification, especially gene targeting via homologous recombination (HR), would be an essential technique...
  83. ncbi Prediction of mammalian microRNA targets
    Benjamin P Lewis
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 115:787-98. 2003
    ..The predicted regulatory targets of mammalian miRNAs were enriched for genes involved in transcriptional regulation but also encompassed an unexpectedly broad range of other functions...
  84. ncbi Development of zinc finger domains for recognition of the 5'-CNN-3' family DNA sequences and their use in the construction of artificial transcription factors
    Birgit Dreier
    The Skaggs Institute for Chemical Biology, La Jolla, California 92037, USA
    J Biol Chem 280:35588-97. 2005
    ..With the addition of this collection of predefined zinc finger domains, most 5'-CNN-3'-, 5'-GNN-3'-, and 5'-ANN-3'-containing sequences can now be rapidly targeted for directed gene regulation and nuclease cleavage...
  85. ncbi Targeted disruption of the gene encoding DNA ligase IV leads to lethality in embryonic mice
    D E Barnes
    Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, UK
    Curr Biol 8:1395-8. 1998
    ..Thus, unlike Ku70/80 and DNA-PKcs [11] [12] [13] [14], DNA ligase IV has an essential function in early mammalian development...
  86. ncbi Defective T cell differentiation in the absence of Jnk1
    C Dong
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA
    Science 282:2092-5. 1998
    ..Thus, the JNK1 signaling pathway plays a key role in T cell receptor-initiated TH cell proliferation, apoptosis, and differentiation...
  87. pmc A single lentiviral vector platform for microRNA-based conditional RNA interference and coordinated transgene expression
    Kum Joo Shin
    Alliance for Cell Signaling Molecular Biology Laboratory, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 103:13759-64. 2006
    ....
  88. pmc Production of CFTR-null and CFTR-DeltaF508 heterozygous pigs by adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer
    Christopher S Rogers
    Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
    J Clin Invest 118:1571-7. 2008
    ..In addition, because gene-modified mice often fail to replicate human diseases, this approach could be used to generate models of other human genetic diseases in species other than mice...
  89. ncbi Simple one-week method to construct gene-targeting vectors: application to production of human knockout cell lines
    Susumu Iiizumi
    Yokohama City University, Yokohama, Japan
    Biotechniques 41:311-6. 2006
    ..Recently, we and others have shown that the human pre-B cell line Nalm-6 allows for high-efficiency gene targeting. The combination of the simplified vector construction system and the high-efficiency gene targeting in the ..
  90. ncbi In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death
    K P Lam
    Institute for Genetics, University of Cologne, Federal Republic of Germany
    Cell 90:1073-83. 1997
    b>Gene targeting experiments have demonstrated that the expression of immunoglobulin heavy chain in the pre-B cell receptor (pBCR) and of heavy and light chains in the B cell antigen receptor (BCR) marks checkpoints in early B cell ..
  91. pmc Attenuation of zinc finger nuclease toxicity by small-molecule regulation of protein levels
    Shondra M Pruett-Miller
    Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
    PLoS Genet 5:e1000376. 2009
    ..ZFNs) have been used successfully to create genome-specific double-strand breaks and thereby stimulate gene targeting by several thousand fold...
  92. ncbi The human pre-B cell line Nalm-6 is highly proficient in gene targeting by homologous recombination
    Noritaka Adachi
    Kihara Institute for Biological Research, Graduate School of Integrated Science, Yokohama City University, Japan
    DNA Cell Biol 25:19-24. 2006
    b>Gene targeting provides a powerful means for analyzing gene function, as exemplified by knockout mouse studies and recent work with the highly recombinogenic chicken DT40 B-lymphocyte line...
  93. pmc Group II intron-based gene targeting reactions in eukaryotes
    Marta Mastroianni
    Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, United States of America
    PLoS ONE 3:e3121. 2008
    ..This feature enabled the development of mobile group II introns into bacterial gene targeting vectors ("targetrons") with programmable target specificity...
  94. pmc Efficient gene targeting mediated by a lentiviral vector-associated meganuclease
    Araksya Izmiryan
    Hopital Necker Enfants Malades, Universite Paris Descartes, 75743 Paris, France
    Nucleic Acids Res 39:7610-9. 2011
    b>Gene targeting can be achieved with lentiviral vectors delivering donor sequences along with a nuclease that creates a locus-specific double-strand break (DSB)...
  95. pmc Molecular basis of engineered meganuclease targeting of the endogenous human RAG1 locus
    Inés G Muñoz
    Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre CNIO, Madrid, Spain
    Nucleic Acids Res 39:729-43. 2011
    ..endonucleases recognize long target DNA sequences generating an accurate double-strand break that promotes gene targeting through homologous recombination...
  96. ncbi Highly proficient gene targeting by homologous recombination in the human pre-B cell line Nalm-6
    Noritaka Adachi
    Kihara Institute for Biological Research, Yokohama City University, Yokohama, Japan
    Methods Mol Biol 435:17-29. 2008
    b>Gene targeting provides a powerful means for studying gene function by a reverse genetic approach...
  97. pmc Zinc-finger nuclease-driven targeted integration into mammalian genomes using donors with limited chromosomal homology
    Salvatore J Orlando
    Sangamo BioSciences, 501 Canal Bvld, Richmond, CA 94804, USA
    Nucleic Acids Res 38:e152. 2010
    ..Up to 50% of deletions contained a donor insertion. Targeted DNA addition via NHEJ complements our homology-directed targeted integration approaches, adding versatility to the manipulation of mammalian genomes...
  98. pmc Gene targeting in the rat: advances and opportunities
    Howard J Jacob
    Department of Dermatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    Trends Genet 26:510-8. 2010
    ..Although the genomic resources of the rat have nearly caught up, gene targeting has lagged far behind, limiting the value of the rat for many investigators...
  99. ncbi Road to precision: recombinase-based targeting technologies for genome engineering
    Dagmar Wirth
    Helmholtz Centre for Infection Research, Department of Gene Regulation and Differentiation and Model Systems for Infection and Immunity, Inhoffenstrasse 7, D 38124 Braunschweig, Germany
    Curr Opin Biotechnol 18:411-9. 2007
    ..In particular, applications for protein expression, virus production, transgenic animals and chromosome engineering are described...
  100. ncbi Robust cell line development using meganucleases
    Jean Pierre Cabaniols
    CELLECTIS S A, Romainville, France
    Methods Mol Biol 435:31-45. 2008
    ..These proteins are powerful tools for genome engineering because they can increase homologous gene targeting by several orders of magnitude in the vicinity of their cleavage site...
  101. ncbi Pluripotent stem cells--model of embryonic development, tool for gene targeting, and basis of cell therapy
    Katja Prelle
    Department of Molecular Animal Breeding and Biotechnology, Ludwig Maximilian University Munich, Hackerstrasse 27, 85764 Oberschleissheim, Germany
    Anat Histol Embryol 31:169-86. 2002
    ....

Research Grants73

  1. Small Molecule targeting of NADPH oxidase in neutrophils
    Marie Dominique Filippi; Fiscal Year: 2010
    ..the Rac GTPases, Rac1 and Rac2, are essential regulators of neutrophil migration and superoxide production in gene targeting studies, (2) our rationally designed Rac-specific small molecule inhibitor, NSC23766, functionally suppressed ..
  2. Lipid Droplet Metabolism
    Fredric B Kraemer; Fiscal Year: 2013
    ..normal adipocytes and within adipocytes in which specific LD-associated proteins have been manipulated by gene targeting. Second, we hypothesize that the formation of CE-rich LDs differs in important and identifiable ways from TAG-..
  3. P38 MAP KINASE SIGNALING IN SKIN
    Tatiana Efimova; Fiscal Year: 2013
    ..cell-specific effects of p384 loss on epithelial carcinogenesis by using conditional tissue-specific p384 gene targeting via the Cre-lox system...
  4. DNA Damage Checkpoint and Cancer
    Toru Ouchi; Fiscal Year: 2012
    ..with other DNA damage-sensing proteins, and whether cell specific-disruption of the BAAT1 pathway using RNA gene targeting approaches facilitates tumor development by genetic and environmental lesions or alters the response to tumors ..
  5. Development of a Porcine Model of Atherosclerosis
    Christopher Rogers; Fiscal Year: 2010
    ..This proposal specifically outlines the development of porcine fibroblasts with a disrupted LDLR gene. A gene targeting vector will be constructed to disrupt the coding region of LDLR...
  6. CELLULAR REGULATION OF CLATHRIN ASSEMBLY AND FUNCTION
    Frances M Brodsky; Fiscal Year: 2013
    ..crystallography and structure-based mutagenesis, RNA interference, membrane traffic and migration assays, and gene targeting strategies to produce animals that can be conditionally depleted of LCa or LCb in specific tissues, followed ..
  7. Role of estrogen-related receptors in cardiac and skeletal muscle
    Janice M Huss; Fiscal Year: 2010
    ..of metabolism using models in which ERR isoforms are selectively activated by overexpression or inhibited by gene targeting or small-interfering RNA...
  8. The Role of CD5 in B-Cell Development and Autoimmunity
    Chander Raman; Fiscal Year: 2012
    ..To test this model, we have generated by gene targeting approach mice expressing CD5 with selective inability to activate the CD5-CK2 dependent prosurvival signaling ..
  9. Role of Heat Shock Transcription Factor Hsf1 in Tumorigenesis
    Nahid F Mivechi; Fiscal Year: 2013
    ..Mutant mice deficient in Hsf1 generated in our laboratory by conventional or conditional gene targeting strategies as well as a knock-in mouse line carrying Hsf1 with the S303A/S307A phosphorylation mutation (..
  10. Development of a Porcine Model of Ataxia-Telangiectasia
    Christopher Rogers; Fiscal Year: 2011
    ..We intend to accomplish this in two steps by combining gene targeting and somatic cell nuclear transfer (SCNT)...
  11. Sphingosine 1-phosphate and cardioprotection
    JOEL SAMUEL KARLINER; Fiscal Year: 2012
    ..an essential role for the enzyme in preconditioning-induced cardioprotection using pharmacological and gene targeting approaches...
  12. Metabolic Pathways and Defects in Fructose Metabolism
    DEAN TOLAN; Fiscal Year: 2009
    ..Lastly, blood samples from African-American and Hispanic-American HFI subjects will be used for identification of gene defects by direct DNA sequencing, thus offering a reliable non-invasive diagnostic method to these Americans. ..
  13. ALS therapies and genomics for mutant TDP-43 and TLS/FUS
    Don W Cleveland; Fiscal Year: 2010
    ..New, very high through put DNA/RNA sequencing methods will be used to identify genes whose expression is altered by the mutations, thereby identifying new targets and approaches for devising a successful therapy for ALS. ..
  14. Development of a Porcine Model of Ataxia-Telangiectasia
    Christopher Rogers; Fiscal Year: 2013
    ....
  15. Innovative approach for high-volume production of endogenous reporter cells
    ROBERT E FINNEY; Fiscal Year: 2012
    ..Compounding this, current gene trapping and gene targeting methods for producing assays require large investments in resources, time, and cost, making them unattainable ..
  16. Beta-Globin Gene Correction Using Peptide Nucleic Acids for the Treatment of Sick
    GERALD FRANCIS VOVIS; Fiscal Year: 2010
    ..combination of triplex and donor DNA molecules, as well as an effective cellular delivery method for our gene targeting molecules...
  17. Functional consequences of autophagy mutations in Crohn's disease.
    David L Boone; Fiscal Year: 2012
    ..Using somatic cell gene targeting, we will generate human intestinal epithelial cells (IEC) that lack ATG16L1, express the ATG16L1 T300A ..
  18. INSULIN RECEPTOR STRUCTURE AND TURNOVER
    C Ronald Kahn; Fiscal Year: 2013
    ..The largest body of studies derived from the use of homologous recombination gene targeting to study the role of the insulin receptor in insulin action in vivo...
  19. Triplex-mediated DNA repair as a novel therapy for Hurler Syndrome patients
    Elizabeth Peterson-Roth; Fiscal Year: 2012
    ..L2 Diagnostics LLC is proposing to develop a therapeutic gene targeting protocol to correct one of the most prominent mutations responsible for HS...
  20. P53 and KRAS Targeted Pigs: A Platform for Models of Human Cancer
    Christopher Rogers; Fiscal Year: 2012
    ..We intend to accomplish this by combining gene targeting and somatic cell nuclear transfer...
  21. Induced Pluripotent Stem Cells from Swine: application to genetic modification
    ROBERT MICHAEL ROBERTS; Fiscal Year: 2013
    ..Aim 3 is to establish parameters for efficient gene targeting and transgenesis in pICM-iPSC...
  22. Functional analysis of Chk2 in DNA damage response
    Jun Hyun Kim; Fiscal Year: 2013
    ..DDR especially in S-phase, using non-transformed conditional knockout cells that will be generated by somatic gene targeting. Using this cell line, I will analyze the acute Chk2 deficiency phenotypes and perform structure- functional ..
  23. Integration of Feeding and Glucose Metabolism by the Circadian Gene Network
    JOSEPH T BASS; Fiscal Year: 2013
    ..we have assembled a unique interdisciplinary team, and now propose to combine conditional tissue-specific gene targeting with an extensive platform for behavioral, physiological and molecular analyses...
  24. Role of LHX3 Protein Isoforms in Pituitary Development
    SIMON JAMES RHODES; Fiscal Year: 2012
    ..further understand the novel form of LHX3-associated disease involving loss of the protein carboxyl terminus, gene targeting techniques will be used to generate a mouse model of the disease carrying an equivalent mutation, allowing ..
  25. Group II Intron Mobility and Gene Targeting
    Alan M Lambowitz; Fiscal Year: 2012
    The proposed research is a continued study of mobile group II introns and their applications in gene targeting. Mobile group II introns are catalytic RNAs ("ribozymes") that encode a reverse transcriptase and are thought to be ..
  26. Blood Coagulation Protein - Metal Ion - Lipid Interactions
    Francis J Castellino; Fiscal Year: 2013
    ..these issues by use of protein chemistry, enzymology, structural biology, molecular/cell biology, and gene targeting strategies...
  27. iPS-derived hepatocytes as a model of familial hypercholesterolemia
    Max A Cayo; Fiscal Year: 2013
    ..hepatocytes can serve as a model for testing and refining the efficacy of the promising AAV class of vectors for somatic gene targeting in vivo, which would significantly accelerate their usefulness as clinical therapies.
  28. GENETIC ASPECTS OF DNA METHYLATION
    Eric U Selker; Fiscal Year: 2013
    ..The work will be facilitated by valuable resources and tools including: 1. Efficient procedures for gene targeting and epitope-tagging;2. A collection of gene knockout strains covering ~80% of the genome;3...
  29. REGULATION OF APOB SECRETION IN INBRED MOUSE STRAINS
    Li Shin Huang; Fiscal Year: 2009
    ..It will also be a potential target for drug discovery and pharmacological intervention in hyperlipidemic patients in the general population. ..
  30. FAH-Deficient Pigs
    Scott L Nyberg; Fiscal Year: 2011
    ..To address the shortage of large animal models, we have utilized a novel strategy combining gene targeting by recombinant adeno-associated virus DJ serotype (rAAVdj) and somatic cell nuclear transfer (SCNT) for the ..
  31. Towards a Mouse Model of Classical Hodgkin's Disease and PTLD
    FREDERICK WAYNE ALT; Fiscal Year: 2013
    ..a strategy to target the expression of candidate genes into GC B cells, using Cre-mediated conditional gene targeting. Using and further improving these tools, we plan to analyze whether induced expression of the various EBV-..
  32. Ribozymes for studies and treatment of cytomegalovirus infections
    Fenyong Liu; Fiscal Year: 2012
    ..Our study will facilitate the development of novel macromolecules that can be used as research tools and therapeutic agents for studies and treatment of infections of human viruses including HCMV. ..
  33. Structure and Function of Endothelial Fenestrae
    RADU VIRGIL STAN; Fiscal Year: 2010
    ..These studies could also help in designing novel strategies for drugs and gene targeting to selected microvascular beds...
  34. Very Late Antigen Integrin Activity on T Cells
    Yoji Shimizu; Fiscal Year: 2010
    ..In Aim 2, we will use conditional gene targeting and adoptive transfer approaches to define the function of beta l integrin expression in controlling integrin- ..
  35. Development of a protein-driven gene targeting technology
    Francesca Storici; Fiscal Year: 2010
    ..genomes can be precisely manipulated inside cells by improving the nuclear delivery, efficiency and safety of gene targeting and expanding its applications...
  36. NEXT GENERATION SEQUENCING ADD-ON-PHARMACOGENOMICS RESEARCH NETWROK (PGRN)
    Elaine R Mardis; Fiscal Year: 2013
    ..abstract_text> ..
  37. Role of ERK1/2 in Neuromuscular Synapses and Myofiber Development in vivo
    Mendell Rimer; Fiscal Year: 2013
    ..However, no gene targeting investigations on the role of ERK1/2 in developing muscle fibers in vivo have been reported to date...
  38. Microinjection Station for Utah Transgenic and Gene Targeting Mouse Core
    SUSAN JENIFER TAMOWSKI; Fiscal Year: 2010
    ..We propose to purchase a Zeiss microinjection station for use in the University of Utah Transgenic and Gene Targeting Mouse Core...
  39. INITIATION OF HUMAN LABOR: PREVENTION OF PREMATURITY
    Carole R Mendelson; Fiscal Year: 2013
    ..of the role of hyaluronan (HA) in cervical ripening through elucidation of the effects of cervix-specific gene targeting of the key regulatory enzyme, hyaluronan synthase 2, and altered expression of HA degradative enzymes, ..
  40. A CENTER OF MOLECULAR DEVELOPMENTAL HEMATOPOIESIS
    Stuart H Orkin; Fiscal Year: 2013
    ..CORE A is a Mouse Embryonic Stem (ES) Cell and Gene Targeting Core that has supported investigators through education and consultation, oocyte and blastocyst ..
  41. Thyroid hormone receptors - regulation and function
    Mitchell A Lazar; Fiscal Year: 2013
    ..We propose to use gene targeting and mouse phenotyping to understand the physiological relevance of the HDACS corepressor complexes...
  42. Olfactory Coding in Mammals
    Minghong Ma; Fiscal Year: 2013
    ..These studies will also help to design better therapeutic agents targeting other G protein-coupled receptors, which play pivotal roles in signal transduction in all body organs. ..
  43. IN VIVO ANALYSIS OF MOUSE H1 HISTONE FUNCTION
    Arthur I Skoultchi; Fiscal Year: 2013
    ..to generate and characterize mice and ES cell lines in which one or more H1 genes have been inactivated by gene targeting. We have generated a large collection of mouse strains consisting of both single null mutants (6 of the 8 ..
  44. Sensory cell fate specification in the inner ear
    Douglas J Epstein; Fiscal Year: 2012
    ..and Hh signaling pathways at later stages of inner ear development in the mouse, using a conditional gene targeting strategy that inactivates essential mediators of these pathways at defined periods of cochlear and vestibular ..
  45. Chemical-genetic functional annotation of the genome of a meningitis pathogen
    Hiten D Madhani; Fiscal Year: 2013
    ..Using optimized methods for gene targeting, our laboratory constructed a library 1201 gene deletion strains...
  46. The roles of lipid metabolism in the maintenance of hematopoietic stem cells
    Keisuke Ito; Fiscal Year: 2013
    ..Teruya-Feldstein (Hemato- pathology), Toshio Suda (Stem Cells), Jan Vijg (Genetics), and Winfried Edelman (Gene Targeting). Importantly, Dr. Paul S. Frenette (Stem Cell niche) is closely supporting our research program along with Dr...
  47. The role of the first mammalian N-term. methyltransferase, NRMT, in tumorigenesis
    Christine E Schaner-Tooley; Fiscal Year: 2012
    ..The UVA Gene Targeting and Transgenic Facility will create the NRMT knockout mouse...
  48. Targeted Manipulation of the Zebrafish Genome through Homologous Recombination
    Brian Ciruna; Fiscal Year: 2010
    ..We will then attempt to streamline the gene targeting strategy by utilizing Tol2 transposase activity to mobilize the vasa-GFP targeting vector...
  49. SEQUENCES CONTROLLING H19 GENE IMPRINTING
    Marisa S Bartolomei; Fiscal Year: 2013
    ..CTCF binding sites but within the ICR and assessing function in vitro by repression assays and in vivo through gene targeting experiments...
  50. MicroRNA-mediated regulation of ATG16L1 expression and autophagy
    John Kwon; Fiscal Year: 2012
    ..assays and generating intestinal epithelial cells harboring the microRNA binding site SNPs using somatic cell gene targeting. Such results are expected to have an important positive impact because the determination of microRNA ..
  51. Cryptococcus neoformans Gene Knockout Resource
    Hiten D Madhani; Fiscal Year: 2013
    ..Using optimized particle bombardment methods for gene targeting, our laboratory demonstrated the feasibility of creating large numbers of bar-coded gene deletions in this ..
  52. Generation of hESC reporter lines using improved gene targeting technology
    TOBIAS DIETMAR RAABE; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Generation of hESC reporter lines using improved gene targeting technology We propose here to develop hESC reporter lines that allow accurate real time measurement of the activity of tissue - specific ..
  53. Determinants of Germinal Center B Cell Differentiation
    Robert C Rickert; Fiscal Year: 2013
    ..Novel approaches utilizing immunoglobulin knock-in mice, inducible B cell-specific gene targeting, conditional retroviral gene expression and germinal center B cell purification techniques enhance the ..
  54. SUSCEPTIBILITY GENES IN AUTOIMMUNE THYROID DISEASE
    TERRY FRANCIS DAVIES; Fiscal Year: 2013
    ..We will examine this possibility directly by TSHR gene targeting and indirectly by using thyroid cell transient siRNA transfection models with TSHR expression and signal ..
  55. Oxidative Stress and Vascular HO in Diabetes
    Nader G Abraham; Fiscal Year: 2010
    ..It will allow for the first time, an in-depth analysis of the function of HO-1 in vascular protection and for the development of innovative gene-targeting therapies for the treatment of type I diabetes. ..
  56. DNA-based MR Probes for Imaging mRNA Transcripts in vivo
    Philip K Liu; Fiscal Year: 2013
    ..Completion of the proposed work provides a platform for novel gene targeting probes as well as a powerful tool for early evaluation of astroglia activation in vivo...
  57. Nuclear Receptor Control of Glucose and Lipid Metabolism
    Enrique Saez; Fiscal Year: 2012
    ..In Specific Aim 4, LXR mutants with altered ligand responses will be used to create using gene targeting animal models to dissect the role of LXR in glucose and cholesterol metabolism in vivo...
  58. Keratin Gene Targeting for the Treatment of Epidermolysis Bullosa
    Daniel G Miller; Fiscal Year: 2013
    ..correct the phenotype of EBS-patient keratinocytes and prepare them for autologous transplantation by using a gene targeting approach...
  59. CONTROL OF MUSCLE PROTEIN SYNTHESIS DURING MYOGENESIS
    Charles P Emerson; Fiscal Year: 2010
    ..screens, will be investigated by antisense inhibition and misexpression analyses in avian embryos and by gene targeting and genetic analyses in the mouse embryo to determine their specific functions in MyoD and MyfS regulation ..
  60. RhoH GTPase in Hematopoiesis and Cancer
    David A Williams; Fiscal Year: 2013
    ..abstract_text> ..
  61. Targeting the Pial Collateral Circulation for Mitigation of Cerebral Ischemia
    James E Faber; Fiscal Year: 2013
    ..I and II will thus identify the highest priority candidates that Am III will test for causality using in vivo gene targeting, cellular analyses, and functional outcomein stroke...
  62. Cytoskeletal Regulation of Erythrocyte Glucose Transporter-1
    Athar H Chishti; Fiscal Year: 2012
    ..of dematin, we propose to generate a new mouse model with complete dematin deficiency using the conventional gene targeting techniques...
  63. Prevention of heart failure and death by sphingolipids: outcomes and mechanisms.
    JOEL KARLINER; Fiscal Year: 2009
    ..an essential role for this enzyme in preconditioning-induced cardioprotection using pharmacological and gene targeting approaches...
  64. GABAA RECEPTOR BETA-SUBUNIT AND GENERAL ANESTHETICS
    Jay Yang; Fiscal Year: 2002
    ..The experiments proposed will add quantitative and mechanistic information to general anesthetic molecular pharmacology and move this field of investigation closer towards truly understanding how these clinically essential drugs work. ..
  65. Role of Y chromosomal genes in male fertility
    Alexander I Agoulnik; Fiscal Year: 2010
    ..Despite numerous attempts Y chromosome gene targeting using conventional ES cell technology did not result in live mouse mutant...
  66. FUNCTION OF MATRIX ATTACHMENT REGIONS IN THE IG LOCI
    ANN FEENEY; Fiscal Year: 2000
    ..and IgH intronic enhancer-associated MARs as transgenes, stable integrants in cell lines, and recently gene targeting, and these studies suggest a role for the MARS in transcriptional enhancement, chromatin remodeling, ..
  67. IMMUNOGLOBULIN GENE TARGETING INTO THE MOUSE GERM LINE
    Matthias Wabl; Fiscal Year: 1992
    DESCRIPTION (Adapted from applicants abstract): By means of gene targeting into the immunoglobulin locus of the mouse germ line, a solution of three longstanding problems in B lymphocyte differentiation is attempted: the mechanism of ..
  68. Large Animal Model of Spinal Muscular Atrophy
    MONIQUE LORSON; Fiscal Year: 2009
    ..b>Gene targeting using murine embryonic stem cells is the most developed and utilized approach and has provided models of human ..
  69. Group II Intron-Based Gene Targeting Methods for Xenopus
    Alan Lambowitz; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): We propose to develop efficient group II intron-based gene targeting methods for Xenopus laevis and Xenopus tropicalis...
  70. Zebrafish ES cell lines for targeted mutagenesis
    Paul Collodi; Fiscal Year: 2010
    ..The goal of this research is to develop gene targeting methods using zebrafish embryonic stem (ES) cell and primordial germ cell (PGC) lines...
  71. Ovarian failure in LH/hCG receptor knockout animals
    CH RAO; Fiscal Year: 2005
    Both IIpo Huhtaniemi's and our group recently succeeded in generating LH receptor knockout mice by gene targeting in embryonic stem cells. Although this gene knockout was not lethal, it rendered animals infertile...
  72. MOUSE MODEL OF IGA DEFICIENCY USING GENE TARGETING
    Gregory Harriman; Fiscal Year: 1993
    ..The immediate objective of this project is to develop a mouse model of IgA deficiency using gene targeting to functionally delete the immunoglobulin heavy chain (Igh) IgA locus from mice...
  73. MECHANISMS OF GENE TARGETING BY RNA-DNA OLIGONUCLEOTIDE
    Kyonggeun Yoon; Fiscal Year: 2001
    DESCRIPTION (Adapted from the Applicant's Abstract): A gene targeting strategy employing RNA-DNA oligonucleotides (RDO) has been developed to modify single-base mutations in chromosomal DNA...