C Baum

Summary

Affiliation: Hannover Medical School
Country: Germany

Publications

  1. ncbi request reprint Gene therapy targeting hematopoietic cells: better not leave it to chance
    Christopher Baum
    Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Acta Haematol 110:107-9. 2003
  2. ncbi request reprint Side effects of retroviral gene transfer into hematopoietic stem cells
    Christopher Baum
    Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Blood 101:2099-114. 2003
  3. ncbi request reprint Mutagenesis and oncogenesis by chromosomal insertion of gene transfer vectors
    Christopher Baum
    Experimental Cell Therapy, Department of Hematology and Oncology, Hannover Medical School, 30625 Hannover, Germany
    Hum Gene Ther 17:253-63. 2006
  4. ncbi request reprint Retrovirus vectors: toward the plentivirus?
    Christopher Baum
    Department of Experimental Hematology, Hannover Medical School, D 30625 Hannover, Germany
    Mol Ther 13:1050-63. 2006
  5. ncbi request reprint Mutagenesis by retroviral transgene insertion: risk assessment and potential alternatives
    Christopher Baum
    Department of Hematology and Oncology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Curr Opin Mol Ther 5:458-62. 2003
  6. ncbi request reprint Insertional mutagenesis in gene therapy and stem cell biology
    Christopher Baum
    Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Curr Opin Hematol 14:337-42. 2007
  7. ncbi request reprint [Gene therapy of SCID-X1]
    C Baum
    Medizinische Hochschule Hannover, BRD
    Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 50:1507-17. 2007
  8. doi request reprint [Advancement of the medical doctorate]
    C Baum
    Abt Experimentelle Hämatologie, Medizinische Hochschule Hannover, 30625 Hannover
    Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 52:856-61. 2009
  9. doi request reprint Concise review: managing genotoxicity in the therapeutic modification of stem cells
    Christopher Baum
    Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Stem Cells 29:1479-84. 2011
  10. pmc Parachuting in the epigenome: the biology of gene vector insertion profiles in the context of clinical trials
    Christopher Baum
    Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    EMBO Mol Med 3:75-7. 2011

Detail Information

Publications86

  1. ncbi request reprint Gene therapy targeting hematopoietic cells: better not leave it to chance
    Christopher Baum
    Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Acta Haematol 110:107-9. 2003
    ..Interestingly, correction of genetic disorders by homologous gene repair in defined stem cell clones is on the horizon, but far from being available for clinical use...
  2. ncbi request reprint Side effects of retroviral gene transfer into hematopoietic stem cells
    Christopher Baum
    Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Blood 101:2099-114. 2003
    ....
  3. ncbi request reprint Mutagenesis and oncogenesis by chromosomal insertion of gene transfer vectors
    Christopher Baum
    Experimental Cell Therapy, Department of Hematology and Oncology, Hannover Medical School, 30625 Hannover, Germany
    Hum Gene Ther 17:253-63. 2006
    ..Improving vector design appears to be the most straightforward approach to increase safety, provided all relevant cofactors are considered...
  4. ncbi request reprint Retrovirus vectors: toward the plentivirus?
    Christopher Baum
    Department of Experimental Hematology, Hannover Medical School, D 30625 Hannover, Germany
    Mol Ther 13:1050-63. 2006
    ..Many of the above goals will require the inclusion of nonretroviral components into vector particles or transgenes...
  5. ncbi request reprint Mutagenesis by retroviral transgene insertion: risk assessment and potential alternatives
    Christopher Baum
    Department of Hematology and Oncology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Curr Opin Mol Ther 5:458-62. 2003
    ..Ongoing research aims to reduce side effects of therapeutic transgene insertion by dose optimization and definition of contributing risk factors...
  6. ncbi request reprint Insertional mutagenesis in gene therapy and stem cell biology
    Christopher Baum
    Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Curr Opin Hematol 14:337-42. 2007
    ..This review summarizes novel studies of underlying mechanisms; these studies have demonstrated the possibility of improved gene vector biosafety and generated new insights into stem cell biology...
  7. ncbi request reprint [Gene therapy of SCID-X1]
    C Baum
    Medizinische Hochschule Hannover, BRD
    Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 50:1507-17. 2007
    ..In future clinical trials, improved vector technology in combination with other protocol modifications may reduce the risk of this side effect...
  8. doi request reprint [Advancement of the medical doctorate]
    C Baum
    Abt Experimentelle Hämatologie, Medizinische Hochschule Hannover, 30625 Hannover
    Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 52:856-61. 2009
    ..Evaluating the achievements and career paths of the trainees will contribute to the successful integration of research work in an efficiency-oriented clinical environment...
  9. doi request reprint Concise review: managing genotoxicity in the therapeutic modification of stem cells
    Christopher Baum
    Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Stem Cells 29:1479-84. 2011
    ..d) Improved approaches for the genetic modification of stem cells can address all critical steps in the origin and growth control of mutants...
  10. pmc Parachuting in the epigenome: the biology of gene vector insertion profiles in the context of clinical trials
    Christopher Baum
    Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    EMBO Mol Med 3:75-7. 2011
    ..This explains the great interest ina deeper understanding of retroviral vector–host interactions in the therapeutic setting of SCID-ADA...
  11. ncbi request reprint Towards hematopoietic stem cell-mediated protection against infection with human immunodeficiency virus
    A Schambach
    Department of Hematology, Hemostaseology and Oncology, Hannover Medical School, Hannover, Germany
    Gene Ther 13:1037-47. 2006
    ..These data encourage further investigations in large animal models and clinical trials...
  12. doi request reprint Leukemia induction after a single retroviral vector insertion in Evi1 or Prdm16
    U Modlich
    Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Leukemia 22:1519-28. 2008
    ..Our study also shows that insertional mutagenesis is required for leukemia induction by IL2RG vectors, a risk to be addressed by improved vector design...
  13. doi request reprint Activation of Evi1 inhibits cell cycle progression and differentiation of hematopoietic progenitor cells
    O S Kustikova
    Institute of Experimental Hematology, Hannover Medical School, Carl Neuberg Strasse 1, Hannover, Germany
    Leukemia 27:1127-38. 2013
    ..Although confined to cultured cells, our study contributes to new hypotheses addressing the mechanisms and molecular targets involved in preleukemic clonal dominance or leukemic transformation by Evi1...
  14. ncbi request reprint Overcoming promoter competition in packaging cells improves production of self-inactivating retroviral vectors
    A Schambach
    Department of Experimental Hematology, Hannover Medical School, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    Gene Ther 13:1524-33. 2006
    ..This study introduces a new generation of efficient gammaretroviral SIN vectors as a platform for further optimizations of retroviral vector performance...
  15. doi request reprint Efficient in vivo regulation of cytidine deaminase expression in the haematopoietic system using a doxycycline-inducible lentiviral vector system
    N Lachmann
    Rebirth Cluster of Excellence, Research Group Reprogramming, Hannover Medical School, Hannover, Germany
    Gene Ther 20:298-307. 2013
    ....
  16. ncbi request reprint Woodchuck hepatitis virus post-transcriptional regulatory element deleted from X protein and promoter sequences enhances retroviral vector titer and expression
    A Schambach
    Department of Hematology, Hemostaseology and Oncology, Hannover Medical School, Hannover, Germany
    Gene Ther 13:641-5. 2006
    ..Furthermore, the X protein promoter could be deleted without compromising the enhancement of vector titers and transgene expression. Such a modified PRE sequence appears useful for future vector design...
  17. doi request reprint Mechanisms controlling titer and expression of bidirectional lentiviral and gammaretroviral vectors
    T Maetzig
    Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Gene Ther 17:400-11. 2010
    ..This allowed for the tracking of chemoprotected and recombined cells by fluorescence marker expression...
  18. ncbi request reprint Persisting multilineage transgene expression in the clonal progeny of a hematopoietic stem cell
    Z Li
    Experimental Cell Therapy, Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Leukemia 16:1655-63. 2002
    ....
  19. ncbi request reprint Leukemias following retroviral transfer of multidrug resistance 1 (MDR1) are driven by combinatorial insertional mutagenesis
    Ute Modlich
    Department of Hematology, Hemostaseology and Oncology, Institute of Cellular and Molecular Pathology, Hannover Medical School, Germany
    Blood 105:4235-46. 2005
    ..On the basis of these findings, we suggest the use of preclinical dose-escalation studies to define a therapeutic index for retroviral transgene delivery...
  20. doi request reprint Selection for Evi1 activation in myelomonocytic leukemia induced by hyperactive signaling through wild-type NRas
    S Wolf
    Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Oncogene 32:3028-38. 2013
    ..As activation of Evi1 has been shown to coincide with NRAS mutations in human acute myeloid leukemia, our murine model recapitulates crucial events in human leukemogenesis...
  21. pmc Vector design for expression of O6-methylguanine-DNA methyltransferase in hematopoietic cells
    Axel Schambach
    Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    DNA Repair (Amst) 6:1187-96. 2007
    ..We conclude that the appropriate design of expression vectors and MGMT protein features will be crucial for the long-term prospects of this promising selection principle...
  22. ncbi request reprint Gene therapy for inherited disorders of haematopoietic cells
    Christoph Klein
    Experimental Hematology and Oncology, Department of Pediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany
    Hematol J 5:103-11. 2004
    ....
  23. pmc Cell-culture assays reveal the importance of retroviral vector design for insertional genotoxicity
    Ute Modlich
    Department of Experimental Hematology, Hannover Medical School, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    Blood 108:2545-53. 2006
    ..Additional modifications of SIN vectors may further increase safety. Improved cell-culture assays will likely play an important role in the evaluation of insertional mutagenesis...
  24. ncbi request reprint Chance or necessity? Insertional mutagenesis in gene therapy and its consequences
    Christopher Baum
    Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany
    Mol Ther 9:5-13. 2004
    ..Based on these considerations, we propose approaches to risk prediction and prevention...
  25. doi request reprint Physiological promoters reduce the genotoxic risk of integrating gene vectors
    Daniela Zychlinski
    Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Mol Ther 16:718-25. 2008
    ..In this manner, the insertional biosafety of therapeutic gene vectors can be greatly enhanced and proactively evaluated in sensitive cell-based assays...
  26. pmc Cell-intrinsic and vector-related properties cooperate to determine the incidence and consequences of insertional mutagenesis
    Olga S Kustikova
    Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Mol Ther 17:1537-47. 2009
    ..Furthermore, our study offers perspectives for refinement of animal experiments in the assessment of vector-related genotoxicity...
  27. ncbi request reprint Predictable and efficient retroviral gene transfer into murine bone marrow repopulating cells using a defined vector dose
    Zhixiong Li
    Experimental Cell Therapy, Department of Hematology and Oncology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Exp Hematol 31:1206-14. 2003
    ..We developed and evaluated a reliable transduction protocol that is more related to clinical methods...
  28. doi request reprint Epidermal growth factor improves lentivirus vector gene transfer into primary mouse hepatocytes
    M Rothe
    Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
    Gene Ther 19:425-34. 2012
    ..Our findings highlight the importance of EGF for efficient LV transduction of primary hepatocytes in culture and should facilitate studies of LV gene transfer in mouse models of monogenetic liver disease...
  29. ncbi request reprint Remarkable leukemogenic potency and quality of a constitutively active neurotrophin receptor, deltaTrkA
    J Meyer
    Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Leukemia 21:2171-80. 2007
    ....
  30. ncbi request reprint LEF-1 is crucial for neutrophil granulocytopoiesis and its expression is severely reduced in congenital neutropenia
    Julia Skokowa
    Department of Pediatric Hematology and Oncology Carl Neuberg Str 1, 30625 Hannover, Germany
    Nat Med 12:1191-7. 2006
    ..These observations indicate that LEF-1 is an instructive factor regulating neutrophilic granulopoiesis whose absence plays a critical role in the defective maturation program of myeloid progenitors in individuals with CN...
  31. ncbi request reprint Safety and efficacy in retrovirally modified haematopoietic cell therapy
    Zhixiong Li
    Department of Haematology, Haemostaseology and Oncology, Hannover Medical School, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    Best Pract Res Clin Haematol 17:493-503. 2004
    ....
  32. pmc High-affinity neurotrophin receptors and ligands promote leukemogenesis
    Zhixiong Li
    Department ofExperimental Hematology, Hannover Medical School, Hannover, Germany
    Blood 113:2028-37. 2009
    ..Moreover, activation of TRKs was important for survival of both human and murine leukemic cells. Our findings suggest that TRKs play an important role in leukemogenesis and may serve as a new drug target...
  33. doi request reprint Generation and genetic modification of induced pluripotent stem cells
    Axel Schambach
    Hannover Medical School, Department of Experimental Hematology, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    Expert Opin Biol Ther 10:1089-103. 2010
    ..iPSCs represent an almost inexhaustible source of cells for targeted differentiation into somatic effector cells and hence are likely to be invaluable for therapeutic applications and disease-related research...
  34. pmc Retroviral vector insertion sites associated with dominant hematopoietic clones mark "stemness" pathways
    Olga S Kustikova
    Department of Experimental Hematology, Hannover Medical School, Germany
    Blood 109:1897-907. 2007
    ..The IDDb forms a powerful resource for the identification of genes that stimulate or transform hematopoietic stem/progenitor cells and is an important reference for vector biosafety studies in human gene therapy...
  35. ncbi request reprint Insertional mutagenesis by replication-deficient retroviral vectors encoding the large T oncogene
    Zhixiong Li
    Department of Experimental Hematology, OE6960, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Ann N Y Acad Sci 1106:95-113. 2007
    ..These findings have important implications for the use of retroviral transgenesis in cancer research, and the expression of signaling genes in somatic gene therapy...
  36. ncbi request reprint Control of self-renewal and differentiation of hematopoietic stem cells: HOXB4 on the threshold
    Hannes Klump
    Department of Hematology, Hemostaseology, and Oncology, Laboratory of Experimental Cell Therapy LECT, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Ann N Y Acad Sci 1044:6-15. 2005
    ..Indeed, existing evidence suggests that dosage effects of ectopically expressed transcription factors may be more the rule than an exception...
  37. pmc HOXB4's road map to stem cell expansion
    Bernhard Schiedlmeier
    Department of Experimental Hematology, Hannover Medical School, Carl Neuberg Strasse 1, 30625 Hannover, Germany
    Proc Natl Acad Sci U S A 104:16952-7. 2007
    ..In summary, our results strongly suggest that HOXB4 modulates the response of HSCs to multiple extrinsic signals in a concerted manner, thereby shifting the balance toward stem cell self-renewal...
  38. pmc Preventing and exploiting the oncogenic potential of integrating gene vectors
    Ute Modlich
    Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    J Clin Invest 119:755-8. 2009
    ..These findings will inform future vector design with the goal of limiting genotoxicity for gene therapy or increasing genotoxicity for protooncogene discovery...
  39. pmc Gene therapy of MPL deficiency: challenging balance between leukemia and pancytopenia
    Daniel C Wicke
    Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Mol Ther 18:343-52. 2010
    ..Mice that received BM cells expressing Mpl from the Mpl promoter were free of any previously observed adverse reactions...
  40. pmc Self-inactivating alpharetroviral vectors with a split-packaging design
    Julia D Suerth
    Experimental Hematology, Hannover Medical School, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    J Virol 84:6626-35. 2010
    ..We demonstrate proof of principle for the versatility of alpharetroviral SIN vectors for the genetic modification of murine and human hematopoietic cells at a low multiplicity of infection...
  41. ncbi request reprint Clinical application of lentiviral vectors - concepts and practice
    Axel Schambach
    Department of Experimental Hematology, Hannover Medical School, Germany
    Curr Gene Ther 8:474-82. 2008
    ..Some additional applications that are expected to lead to the initiation of clinical trials in the near future are also discussed...
  42. ncbi request reprint Improving transcriptional termination of self-inactivating gamma-retroviral and lentiviral vectors
    Axel Schambach
    1Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Mol Ther 15:1167-73. 2007
    ..Importantly, the 2xSV USE was superior to the wPRE in suppressing transcriptional read-through, improving not only vector efficiency but potentially also biosafety...
  43. pmc Insertional transformation of hematopoietic cells by self-inactivating lentiviral and gammaretroviral vectors
    Ute Modlich
    Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Mol Ther 17:1919-28. 2009
    ..Mechanistic studies support the conclusion that enhancer-mediated gene activation is the major cause for insertional transformation of hematopoietic cells, opening rational strategies for risk prevention...
  44. ncbi request reprint I could die for you: new prospects for suicide in gene therapy
    Christopher Baum
    Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Mol Ther 15:848-9. 2007
  45. ncbi request reprint Expression of the p75 neurotrophin receptor in acute leukaemia
    Gernot Beutel
    Department of Haematology, Haemostasis and Oncology, Hannover Medical School, Hannover, Germany
    Br J Haematol 131:67-70. 2005
    ..These results support further detailed analyses of neurotrophin receptors and downstream signalling pathways in haematological malignancies...
  46. doi request reprint EVI-1 modulates leukemogenic potential and apoptosis sensitivity in human acute lymphoblastic leukemia
    M Konantz
    Department of Hematology and Oncology, University of Tuebingen Medical Center II, Tuebingen, Germany
    Leukemia 27:56-65. 2013
    ..Thus, our data show that EVI-1 is expressed not only in myeloid but also in lymphoid leukemias, and contributes to the leukemogenic potential and apoptosis resistance of ALL cells...
  47. pmc Cellular restriction of retrovirus particle-mediated mRNA transfer
    Melanie Galla
    Department of Experimental Hematology, Hannover Medical School, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    J Virol 82:3069-77. 2008
    ..Our data imply that retroviral nucleic acids become accessible to host factors, including ribosomes, as a result of particle remodeling during cytoplasmic trafficking...
  48. ncbi request reprint Lentiviral vectors pseudotyped with murine ecotropic envelope: increased biosafety and convenience in preclinical research
    Axel Schambach
    Department of Hematology, Hemostaseology and Oncology, Hannover Medical School, Germany
    Exp Hematol 34:588-92. 2006
    ..However, this method has found little acceptance, despite potential advantages...
  49. pmc Inhibition of human immunodeficiency virus type 1 entry in cells expressing gp41-derived peptides
    Marc Egelhofer
    Institute for Biomedical Research Georg Speyer Haus, Frankfurt a M Medizinische Hochschule Hannover, Hannover, Germany
    J Virol 78:568-75. 2004
    ..Preclinical toxicity and efficacy studies of this antiviral vector have been completed, and clinical trials are in preparation...
  50. doi request reprint Retroviral integration site analysis in hematopoietic stem cells
    Olga S Kustikova
    Department of Experimental Hematology, Hannover Medical School, Hannover, Germany
    Methods Mol Biol 430:255-67. 2008
    ..In murine bone marrow transplantation models, we have shown that this method is very useful to analyze the impact of retroviral insertion sites on both malignant and benign clonal dominance of individual repopulating HSC...
  51. ncbi request reprint Murine leukemia virus regulates alternative splicing through sequences upstream of the 5' splice site
    Janine Kraunus
    Department of Experimental Hematology, Hannover Medical School, D 30625 Hannover, Germany
    J Biol Chem 281:37381-90. 2006
    ..Together, these findings suggest that sequences upstream of the 5' splice site play an important role in splice regulation of simple retroviruses, directly or indirectly attenuating the efficiency of splicing...
  52. doi request reprint Multiplexing RMCE: versatile extensions of the Flp-recombinase-mediated cassette-exchange technology
    Soeren Turan
    Hannover Medical School OE6960 Experimental Hematology, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    J Mol Biol 402:52-69. 2010
    ..e., the simultaneous exchange of two separate target cassettes in a given cell)...
  53. ncbi request reprint Genetic protection of repopulating hematopoietic cells with an improved MDR1-retrovirus allows administration of intensified chemotherapy following stem cell transplantation in mice
    Alexander Carpinteiro
    Department of Cell and Virus Genetics, Heinrich Pette Institute, Hamburg, Germany
    Int J Cancer 98:785-92. 2002
    ..Our mouse model, mimicking clinically achievable gene transfer rates, thus suggests that bone marrow chemoprotection may widen the therapeutic window and permit an earlier onset of post-transplantation chemotherapy...
  54. ncbi request reprint Multidrug resistance 1 gene transfer can confer chemoprotection to human peripheral blood progenitor cells engrafted in immunodeficient mice
    Bernd Schiedlmeier
    German Cancer Research Center, 69120 Heidelberg, Germany
    Hum Gene Ther 13:233-42. 2002
    ..This is the first report showing that cytostatic drug resistance gene therapy can mediate chemoprotection of human clinically relevant stem cell populations with marrow engraftment potential...
  55. ncbi request reprint High-level ectopic HOXB4 expression confers a profound in vivo competitive growth advantage on human cord blood CD34+ cells, but impairs lymphomyeloid differentiation
    Bernhard Schiedlmeier
    Heinrich Pette Institute, Department of Cell and Virus Genetics, Hamburg, Germany
    Blood 101:1759-68. 2003
    ..01). These results show for the first time unwanted side effects of ectopic HOXB4 expression and therefore underscore the need to carefully determine the therapeutic window of HOXB4 expression levels before initializing clinical trials...
  56. doi request reprint Resistance of mature T cells to oncogene transformation
    Sebastian Newrzela
    Georg Speyer Haus, Institute for Biomedical Research, Frankfurt, Germany
    Blood 112:2278-86. 2008
    ..Thus, our data provide direct evidence that mature T cells are less prone to transformation than hematopoietic progenitor cells...
  57. ncbi request reprint Murine leukemia induced by retroviral gene marking
    Zhixiong Li
    Heinrich Pette Institute, D 20251 Hamburg, Germany
    Science 296:497. 2002
  58. doi request reprint Reciprocal relationship between O6-methylguanine-DNA methyltransferase P140K expression level and chemoprotection of hematopoietic stem cells
    Michael D Milsom
    Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio, USA
    Cancer Res 68:6171-80. 2008
    ..These studies have direct translational relevance to ongoing clinical gene therapy studies using MGMT(P140K), whereas the novel mechanistic findings are relevant to the basic understanding of DNA repair by MGMT...
  59. ncbi request reprint Upstream conserved sequences of mouse leukemia viruses are important for high transgene expression in lymphoid and hematopoietic cells
    Anke Wahlers
    Heinrich Pette Institute, Department of Cell and Virus Genetics, 20251 Hamburg, Germany
    Mol Ther 6:313-20. 2002
    ..These results provide novel clues for the manipulation of retrovirus replication and vector tropism...
  60. ncbi request reprint Down-regulation of retroviral transgene expression during differentiation of progenitor-derived dendritic cells
    Carsten Lindemann
    EUFETS AG, Idar Oberstein, Germany
    Exp Hematol 30:150-7. 2002
    ..We investigated the expression of enhanced green fluorescence protein (EGFP) mediated by retroviral vectors in dendritic cells and other hematopoietic cells differentiated in vitro...
  61. doi request reprint Self-inactivating gammaretroviral vectors for gene therapy of X-linked severe combined immunodeficiency
    Susannah I Thornhill
    Centre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Mol Ther 16:590-8. 2008
    ....
  62. ncbi request reprint Dose finding with retroviral vectors: correlation of retroviral vector copy numbers in single cells with gene transfer efficiency in a cell population
    Olga S Kustikova
    Department of Bone Marrow Transplantation, University Hospital Hamburg Eppendorf, D 20251 Hamburg, Germany
    Blood 102:3934-7. 2003
    ..Therefore, limiting retroviral gene transfer to approximately 30% may be suggested to avoid generating clones containing multiple insertions...
  63. ncbi request reprint Engineered long terminal repeats of retroviral vectors enhance transgene expression in hepatocytes in vitro and in vivo
    Kanji Yamaguchi
    Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, 606 8507, Kyoto, Japan
    Mol Ther 8:796-803. 2003
    ..5- to 5-fold in comparison with a Moloney murine leukemia virus-based vector or a vector containing the wild-type LTR of SFFVp, respectively, in murine hepatocytes in vivo...
  64. pmc Lenti in red: progress in gene therapy for human hemoglobinopathies
    Christof von Kalle
    Division of Expermental Hematology, Cincinnati Children s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    J Clin Invest 114:889-91. 2004
    ..While some safety concerns must be addressed, this study is an important step toward potential clinical trials of gene therapy for hemoglobinopathies...
  65. pmc In vivo analysis of retroviral enhancer mutations in hematopoietic cells: SP1/EGR1 and ETS/GATA motifs contribute to long terminal repeat specificity
    Anke Wahlers
    Department of Cell and Virus Genetics, Heinrich Pette Institute, D 20251 Hamburg, Germany
    J Virol 76:303-12. 2002
    ....
  66. ncbi request reprint The message is sufficient: towards nontoxic delivery of endonucleases
    Christopher Baum
    Mol Ther 13:461-2. 2006
  67. ncbi request reprint HOXB4 inhibits cell growth in a dose-dependent manner and sensitizes cells towards extrinsic cues
    Elke Will
    Department of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio, USA
    Cell Cycle 5:14-22. 2006
    ..Based on these results we propose that HOXB4 affects cell growth in a dose-dependent manner by sensitizing cells towards extrinsic signals...
  68. ncbi request reprint Simplified generation of high-titer retrovirus producer cells for clinically relevant retroviral vectors by reversible inclusion of a lox-P-flanked marker gene
    Rainer Loew
    EUFETS AG, Vollmersbachstrasse 66, D 55743 Idar Oberstein, Germany
    Mol Ther 9:738-46. 2004
    ..The single lox-P site retained in the vector backbone does not affect gene expression level or fidelity of RNA processing...
  69. pmc HOXB4 enforces equivalent fates of ES-cell-derived and adult hematopoietic cells
    Sandra Pilat
    Research Institute of Molecular Pathology, Vienna Biocenter, Dr Bohr Gasse 7, 1030 Vienna, Austria
    Proc Natl Acad Sci U S A 102:12101-6. 2005
    ..Provided that HOXB4 levels are kept within a certain therapeutic window, ES cells also carry the potential of efficient and safe somatic gene therapy...
  70. ncbi request reprint Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking
    Olga Kustikova
    Bone Marrow Transplantation, University Hospital Eppendorf, Martinistrasse 52, 20251 Hamburg, Germany
    Science 308:1171-4. 2005
    ..Transcriptional dysregulation occurred in all 12 insertion sites analyzed. These findings have major implications for diagnostic gene marking and the discovery of genes regulating stem cell turnover...
  71. ncbi request reprint In vivo selection of transduced hematopoietic stem cells and little evidence of their conversion into hepatocytes in vivo
    Kanji Yamaguchi
    Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, Kyoto, Japan
    J Hepatol 45:681-7. 2006
    ..Here, we examined whether these vectors could provide a sufficient drug-resistance gene expression in HSCs and whether transduced HSCs could differentiate into hepatocytes in vivo...
  72. ncbi request reprint Medicine. Gene therapy--new challenges ahead
    David A Williams
    Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Science 302:400-1. 2003
    ..reinforces the need to develop even more specific gene therapy interventions...
  73. ncbi request reprint Retroviral vectors for high-level transgene expression in T lymphocytes
    Boris Engels
    Max Delbruck Center for Molecular Medicine, Robert Rossle Strasse 10, 13092 Berlin, Germany
    Hum Gene Ther 14:1155-68. 2003
    ..In summary, MP71 vectors are useful tools for stable, high-level gene expression in T lymphocytes, for example, in the expression of T cell receptor genes...
  74. ncbi request reprint CD34 modulates the trafficking behavior of hematopoietic cells in vivo
    Claudia Lange
    Bone Marrow Transplantation, University Medical Center Hamburg Eppendorf, 20246 Hamburg, Germany
    Stem Cells Dev 16:297-304. 2007
    ..Our data indicate that CD34 expression in mature blood cells has a suppressive effect on cellular trafficking to hematopoietic stroma organs, thereby supporting a modulating role of the CD34 molecule in cytoadhesion...
  75. ncbi request reprint MN1 overexpression induces acute myeloid leukemia in mice and predicts ATRA resistance in patients with AML
    Michael Heuser
    Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada
    Blood 110:1639-47. 2007
    ..MN1 is a unique oncogene in hematopoiesis that both promotes proliferation/self-renewal and blocks differentiation, and may become useful as a predictive marker in AML treatment...
  76. ncbi request reprint Overexpression of MDR1 using a retroviral vector differentially regulates genes involved in detoxification and apoptosis and confers radioprotection
    Patrick Maier
    Department of Radiation Oncology, Mannheim Medical Centre, University of Heidelberg, 68167 Mannheim, Germany
    Radiat Res 166:463-73. 2006
    ..These results have important implications for understanding the mechanisms by which MDR1 gene therapy can protect normal tissues from radiation- or chemotherapy-induced damage during tumor treatment...
  77. ncbi request reprint Importance of murine study design for testing toxicity of retroviral vectors in support of phase I trials
    Elke Will
    Division of Experimental Hematology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    Mol Ther 15:782-91. 2007
    ....
  78. ncbi request reprint Gene therapy: X-SCID transgene leukaemogenicity
    Adrian J Thrasher
    Molecular Immunology Unit, Institute of Child Health, University College London, London WC1N 1EH, UK
    Nature 443:E5-6; discussion E6-7. 2006
    ..Here we show that transgenic IL2RG does not necessarily have potent intrinsic oncogenic properties, and argue that the interpretation of this observation with respect to human trials is overstated...
  79. ncbi request reprint What are the consequences of the fourth case?
    Christopher Baum
    Mol Ther 15:1401-2. 2007
  80. ncbi request reprint Gene therapy needs both trials and new strategies
    David Williams
    Nature 429:129. 2004
  81. ncbi request reprint Retroviral pseudotransduction for targeted cell manipulation
    Melanie Galla
    Division of Experimental Hematology, Cincinnati Children s Hospital Research Foundation, Cincinnati, OH 45229, USA
    Mol Cell 16:309-15. 2004
    ..Thus, retrovirally delivered mRNA may serve as an immediate translation template if not being reverse transcribed. This approach allows multiple modifications for targeted and reversible cell manipulation with nucleic acids...
  82. ncbi request reprint Role of the Multidrug Resistance Protein 1 in protection from heavy metal oxyanions: investigations in vitro and in MRP1-deficient mice
    Aurelio Lorico
    Department of Tumor Biology, Norwegian Radium Hospital, Montebello, 0310, Norway
    Biochem Biophys Res Commun 291:617-22. 2002
    ..p. with sodium arsenite. It is conceivable that, in vivo, other pump(s) effectively vicariate for MRP1-mediated transport of heavy metal oxyanions...
  83. ncbi request reprint Gamma-glutamylcysteine synthetase and L-buthionine-(S,R)-sulfoximine: a new selection strategy for gene-transduced neural and hematopoietic stem/progenitor cells
    Aurelio Lorico
    Department of Tumor Biology, Norwegian Radium Hospital, Montebello, Oslo 0310, Norway
    Hum Gene Ther 16:711-24. 2005
    ..These results provide proof of principle that somatic stem/progenitor cells, transduced simultaneously with a potentially curative gene and gamma-GCSh, can be selected by treatment with BSO before in vivo transplantation...
  84. pmc Unmodified Cre recombinase crosses the membrane
    Elke Will
    Department of Cell and Virus Genetics, Heinrich Pette Institute for Experimental Virology and Immunology, Martinistrasse 52, D 20251 Hamburg, Germany
    Nucleic Acids Res 30:e59. 2002
    ..We conclude that Cre enyzme itself or its intrinsic membrane-permeating moiety are attractive tools for direct manipulation of mammalian cells...
  85. ncbi request reprint Transfer of autologous gene-modified T cells in HIV-infected patients with advanced immunodeficiency and drug-resistant virus
    Jan van Lunzen
    Infectious Diseases Unit, University Medical Center Hamburg Eppendorf, Hamburg, Germany
    Mol Ther 15:1024-33. 2007
    ..In conclusion, the transfer of gene-modified cells was safe, led to sustained levels of gene marking, and may improve immune competence in HIV-infected patients with advanced disease and multidrug-resistant virus...
  86. ncbi request reprint Tumor cells escape suicide gene therapy by genetic and epigenetic instability
    Oliver Frank
    Department of Cell and Virus Genetics, Heinrich Pette Institute, Hamburg, Germany
    Blood 104:3543-9. 2004
    ..Considering the mechanisms of escape identified here, the proactive use of suicide genes to prevent complications of insertional mutagenesis may still be efficient...