D B Kohn

Summary

Affiliation: University of Southern California
Country: USA

Publications

  1. ncbi request reprint Adenosine deaminase gene therapy protocol revisited
    Donald B Kohn
    Division of Research Immunology B M T, Childrens Hospital Los Angeles, Keck U S C School of Medicine, Los Angeles, California 90027, USA
    Mol Ther 5:96-7. 2002
  2. ncbi request reprint A clinical trial of retroviral-mediated transfer of a rev-responsive element decoy gene into CD34(+) cells from the bone marrow of human immunodeficiency virus-1-infected children
    D B Kohn
    Division of Research Immunology Bone Marrow Transplantation, Childrens Hospital Los Angeles, CA 90027, USA
    Blood 94:368-71. 1999
  3. ncbi request reprint Gene therapy for childhood immunological diseases
    D B Kohn
    Department of Pediatrics, Childrens Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, CA 90027, USA
    Bone Marrow Transplant 41:199-205. 2008
  4. ncbi request reprint Occurrence of leukaemia following gene therapy of X-linked SCID
    Donald B Kohn
    Division of Research Immunology BMT, Childrens Hospital Los Angeles, USC Keck School of Medicine, 4650 Sunset Boulevard, Los Angeles, California 90027, USA
    Nat Rev Cancer 3:477-88. 2003
  5. ncbi request reprint Gene therapy for genetic haematological disorders and immunodeficiencies
    D B Kohn
    Division of Research Immunology Bone Marrow Transplantation, Children s Hospital, Los Angeles, CA, USA
    J Intern Med 249:379-90. 2001
  6. ncbi request reprint Gene therapy using hematopoietic stem cells
    D B Kohn
    Department of Pediatrics, University of Southern California School of Medicine, Children s Hospital, Los Angeles 90027, USA
    Curr Opin Mol Ther 1:437-42. 1999
  7. ncbi request reprint Gene delivery to human B-precursor acute lymphoblastic leukemia cells
    L Mascarenhas
    Divisions of Research Immunology Bone Marrow Transplantation and Hematology Oncology, Department of Pediatrics, University of Southern California School of Medicine, Childrens Hospital Los Angeles, Los Angeles, CA, USA
    Blood 92:3537-45. 1998
  8. doi request reprint Tissue-specific restriction of cyclophilin A-independent HIV-1- and SIV-derived lentiviral vectors
    C A Kahl
    Division of Research Immunology Bone Marrow Transplantation, The Saban Research Institute of Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA
    Gene Ther 15:1079-89. 2008
  9. ncbi request reprint The woodchuck hepatitis virus post-transcriptional regulatory element reduces readthrough transcription from retroviral vectors
    T Higashimoto
    Division of Hematology Oncology, Department of Pediatrics and Pathology, Keck School of Medicine University of Southern California, Childrens Hospital Los Angeles, Los Angeles, CA, USA
    Gene Ther 14:1298-304. 2007
  10. ncbi request reprint T cell depleted haploidentical bone marrow transplantation for the treatment of children with severe combined immunodeficiency
    E M Smogorzewska
    Division of Research Immunology and Bone Marrow Transplantation, Childrens Hospital LA, University of Southern California School of Medicine, Los Angeles 90027, USA
    Arch Immunol Ther Exp (Warsz) 48:111-8. 2000

Research Grants

Collaborators

Detail Information

Publications83

  1. ncbi request reprint Adenosine deaminase gene therapy protocol revisited
    Donald B Kohn
    Division of Research Immunology B M T, Childrens Hospital Los Angeles, Keck U S C School of Medicine, Los Angeles, California 90027, USA
    Mol Ther 5:96-7. 2002
  2. ncbi request reprint A clinical trial of retroviral-mediated transfer of a rev-responsive element decoy gene into CD34(+) cells from the bone marrow of human immunodeficiency virus-1-infected children
    D B Kohn
    Division of Research Immunology Bone Marrow Transplantation, Childrens Hospital Los Angeles, CA 90027, USA
    Blood 94:368-71. 1999
    ..These observations support the potential of performing gene therapy for HIV-1 using hematopoietic cells, but emphasize the need for improved gene transfer techniques...
  3. ncbi request reprint Gene therapy for childhood immunological diseases
    D B Kohn
    Department of Pediatrics, Childrens Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, CA 90027, USA
    Bone Marrow Transplant 41:199-205. 2008
    ..Ultimately, the relative benefits and risks of autologous gene therapy will be weighed against other available options (for example, allogeneic HSCT) to determine the treatment of choice...
  4. ncbi request reprint Occurrence of leukaemia following gene therapy of X-linked SCID
    Donald B Kohn
    Division of Research Immunology BMT, Childrens Hospital Los Angeles, USC Keck School of Medicine, 4650 Sunset Boulevard, Los Angeles, California 90027, USA
    Nat Rev Cancer 3:477-88. 2003
    ..What were the causes of this cancer, and how can the therapeutic benefits of gene therapy be achieved while minimizing risk to the patient?..
  5. ncbi request reprint Gene therapy for genetic haematological disorders and immunodeficiencies
    D B Kohn
    Division of Research Immunology Bone Marrow Transplantation, Children s Hospital, Los Angeles, CA, USA
    J Intern Med 249:379-90. 2001
    ..Newer methods for manipulating HSCs may lead to efficacy for other disorders. The problems and progress in this area are reviewed herein...
  6. ncbi request reprint Gene therapy using hematopoietic stem cells
    D B Kohn
    Department of Pediatrics, University of Southern California School of Medicine, Children s Hospital, Los Angeles 90027, USA
    Curr Opin Mol Ther 1:437-42. 1999
    ..These advances, documented in animal transplant models, are now being applied to clinical trials...
  7. ncbi request reprint Gene delivery to human B-precursor acute lymphoblastic leukemia cells
    L Mascarenhas
    Divisions of Research Immunology Bone Marrow Transplantation and Hematology Oncology, Department of Pediatrics, University of Southern California School of Medicine, Childrens Hospital Los Angeles, Los Angeles, CA, USA
    Blood 92:3537-45. 1998
    ..Both vectors transduced the primary B-precursor ALL cells with high efficiencies. These studies may be applied for investigating gene delivery into primary human B-precursor ALL cells to be used for immunotherapy...
  8. doi request reprint Tissue-specific restriction of cyclophilin A-independent HIV-1- and SIV-derived lentiviral vectors
    C A Kahl
    Division of Research Immunology Bone Marrow Transplantation, The Saban Research Institute of Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA
    Gene Ther 15:1079-89. 2008
    ....
  9. ncbi request reprint The woodchuck hepatitis virus post-transcriptional regulatory element reduces readthrough transcription from retroviral vectors
    T Higashimoto
    Division of Hematology Oncology, Department of Pediatrics and Pathology, Keck School of Medicine University of Southern California, Childrens Hospital Los Angeles, Los Angeles, CA, USA
    Gene Ther 14:1298-304. 2007
    ..Our results showed that WPRE improved vector genomic transcript termination to increase titers and expression from RVs...
  10. ncbi request reprint T cell depleted haploidentical bone marrow transplantation for the treatment of children with severe combined immunodeficiency
    E M Smogorzewska
    Division of Research Immunology and Bone Marrow Transplantation, Childrens Hospital LA, University of Southern California School of Medicine, Los Angeles 90027, USA
    Arch Immunol Ther Exp (Warsz) 48:111-8. 2000
    ..v. Ig injections. Early diagnosis, prevention or treatment of opportunistic infections, and enhancement of immune recovery will be necessary to improve survival in patients with SCID treated with TCD BMT...
  11. ncbi request reprint An in vitro model of human red blood cell production from hematopoietic progenitor cells
    P Malik
    Division of Research Immunology Bone Marrow Transplantation, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA
    Blood 91:2664-71. 1998
    ..This model of human erythropoiesis will allow studies on pathophysiology of congenital RBC disorders and test effective therapeutic strategies...
  12. ncbi request reprint Tolerance induction by lentiviral gene therapy with a nonmyeloablative regimen
    Noboru Mitsuhashi
    Childrens Hospital of Los Angeles, Department of Cardiothoracic Surgery, Los Angeles, CA 90027, USA
    Blood 107:2286-93. 2006
    ..Mice reconstituted with GalT accepted alphaGal+ heart grafts over 100 days. Transduction with lentiviral vectors results in chimerism at levels sufficient to induce long-term tolerance under nonmyeloablative conditions...
  13. pmc Comparison of gene transfer efficiencies and gene expression levels achieved with equine infectious anemia virus- and human immunodeficiency virus type 1-derived lentivirus vectors
    J P O'Rourke
    Children s Research Institute, Children s Hospital, Columbus, Ohio 43205, USA
    J Virol 76:1510-5. 2002
    ..However, our data indicate that transgene expression from EIAV vectors is limited by the instability of vector-derived RNA transcripts and silencing of the EIAV vectors over time...
  14. pmc Lentiviral vectors with amplified beta cell-specific gene expression
    K L Shaw
    Division of Research Immunology Bone Marrow Transplantation, Childrens Hospital Los Angeles, Los Angeles, CA, USA
    Gene Ther 16:998-1008. 2009
    ..In primary human islets, gene expression from the insulin-promoted vectors was coincident with insulin staining. These vectors will be useful in gene-expression studies that require a detectable signal and tissue specificity...
  15. pmc Neonatal bone marrow transplantation of ADA-deficient SCID mice results in immunologic reconstitution despite low levels of engraftment and an absence of selective donor T lymphoid expansion
    Denise A Carbonaro
    Division of Research Immunology Bone Marrow Transplantation, Childrens Hospital, Los Angeles, CA 90027, USA
    Blood 111:5745-54. 2008
    ..Thus, ADA-deficient SCID is unique in its responses to nonmyeloablative bone marrow transplantation, which has implications for clinical bone marrow transplantation or gene therapy...
  16. doi request reprint Long-term neurocognitive function of pediatric patients with severe combined immune deficiency (SCID): pre- and post-hematopoietic stem cell transplant (HSCT)
    Malinda Lin
    Department of Pediatrics, Keck School of Medicine, Los Angeles, CA, USA
    J Clin Immunol 29:231-7. 2009
    ..The purpose of this study was to evaluate long-term neurodevelopment of patients with SCID following myeloablative chemotherapy and HSCT...
  17. ncbi request reprint Gene therapy to inhibit xenoantibody production using lentiviral vectors in non-human primates
    J Y Fischer-Lougheed
    Department of Cardiothoracic Surgery, The Saban Research Institute of Children s Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA
    Gene Ther 14:49-57. 2007
    ..This study is the first to report the application of gene therapy to achieve low-level, long-term gal chimerism sufficient to inhibit production of anti-gal antibodies after immunization with porcine cells in rhesus macaques...
  18. ncbi request reprint Treatment of the mouse model of mucopolysaccharidosis I with retrovirally transduced bone marrow
    Yi Zheng
    Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1737, USA
    Mol Genet Metab 79:233-44. 2003
    ..The partial correction of brain pathology is attributed to migration of donor hematopoietic cells, demonstrated by the presence of the Y chromosome and of normal microglia in the brain of mice receiving IDUA cDNA...
  19. ncbi request reprint In vivo transduction by intravenous injection of a lentiviral vector expressing human ADA into neonatal ADA gene knockout mice: a novel form of enzyme replacement therapy for ADA deficiency
    Denise A Carbonaro
    Division of Research Immunology B M T, Childrens Hospital Los Angeles, California 90027, USA
    Mol Ther 13:1110-20. 2006
    ..These studies illustrate the potential for sustained in vivo production of enzymatically active ADA, as an alternative to therapy by frequent injection of exogenous ADA protein...
  20. ncbi request reprint Constitutive HOXA5 expression inhibits erythropoiesis and increases myelopoiesis from human hematopoietic progenitors
    G M Crooks
    Division of Research Immunology and Bone Marrow Transplantation, Department of Pathology, Division of Hematology Oncology, Childrens Hospital Los Angeles, CA, USA
    Blood 94:519-28. 1999
    ....
  21. ncbi request reprint Hematopoietic stem cell transplantation for severe combined immune deficiency
    K I Weinberg
    Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, 4650 Sunset Blvd, MS#84, Los Angeles, CA 90027, USA
    Curr Allergy Asthma Rep 1:416-20. 2001
    ..Debate still continues about the role of pretransplantation therapy for SCID patients, and the biology of post-HSCT immune reconstitution is under investigation...
  22. ncbi request reprint Retrovirally transduced bone marrow has a therapeutic effect on brain in the mouse model of mucopolysaccharidosis IIIB
    Yi Zheng
    Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 1737, USA
    Mol Genet Metab 82:286-95. 2004
    ..These results show that genetically modified cells of hematopoietic origin can reduce the pathologic manifestations of MPS IIIB in the Naglu -/- mouse brain...
  23. ncbi request reprint [Transplantation of genetically modified cells in the treatment of children with SCID: great hopes and recent disappointments]
    Elzbieta Monika Smogorzewska
    Research Immunology, Children Hospital LA, Los Angeles, CA 90027, USA
    Med Wieku Rozwoj 7:27-34. 2003
    ..This case is being investigated to determine whether the genetic manipulations of the patient's HSC could be the reason for mutagenesis and how other factors could have contributed to this unfortunate event...
  24. ncbi request reprint Gene therapy for inborn and acquired immune deficiency disorders
    Barbara C Engel
    Division of Research Immunology Bone Marrow Transplantation, Children s Hospital Los Angeles, California
    Acta Haematol 110:60-70. 2003
    ..Gene therapy approaches and clinical trials for several inborn as well as acquired immune deficiencies will be reviewed...
  25. ncbi request reprint Update on gene therapy of inherited immune deficiencies
    Barbara C Engel
    Division of Research Immunology Bone Marrow Transplantation, Childrens Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027, USA
    Curr Opin Mol Ther 5:503-7. 2003
    ..Depending upon the results of long-term follow-up, the successes together with the side effects highlight the relative merits of this therapeutic approach...
  26. ncbi request reprint Busulfan and cyclophosphamide as a conditioning regimen for pediatric acute lymphoblastic leukemia patients undergoing bone marrow transplantation
    Ami J Shah
    Department of Pediatrics, Keck School of Medicine, Dallas, Texas, USA
    J Pediatr Hematol Oncol 26:91-7. 2004
    ..Other long-term side effects, such as endocrinopathies and secondary malignancies, were also minimal. These data show that the Bu/Cy regimen is well tolerated, but the overall survival rate remains low...
  27. ncbi request reprint Use of lentiviral vectors to induce long-term tolerance to gal(+) heart grafts
    Mary Kearns-Jonker
    Department of Cardiothoracic Surgery, Children s Hospital of Los Angeles and the University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA
    Transplantation 77:1748-54. 2004
    ..Limitations to the success of this methodology include short-term expression of the introduced gene and rejection of gal hearts transplanted into these animals within a month...
  28. ncbi request reprint Transient gene expression by nonintegrating lentiviral vectors
    Sarah J Nightingale
    Division of Research Immunology Bone Marrow Transplant, The Saban Research Institute of Children s Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA
    Mol Ther 13:1121-32. 2006
    ..The development of NIL vectors provides a novel tool for efficient transient gene expression in primary stem cells and hematopoietic and lymphoid cells...
  29. ncbi request reprint Expression from second-generation feline immunodeficiency virus vectors is impaired in human hematopoietic cells
    Mary A Price
    Division of Research Immunology Bone Marrow Transplantation, Childrens Hospital Los Angeles, Los Angeles, California 90027, USA
    Mol Ther 6:645-52. 2002
    ..We conclude that FIV vectors can transfer genes into human hematopoietic cells as effectively as HIV-1 vectors, but that unknown elements in the current FIV backbone inhibit expression from FIV vectors in human hematopoietic cells...
  30. ncbi request reprint Dynamic tracking of human hematopoietic stem cell engraftment using in vivo bioluminescence imaging
    Xiuli Wang
    Division of Research Immunology BMT, Department of Radiology, and Congresman Dixon Cellular Imaging Core, Childrens Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027, USA
    Blood 102:3478-82. 2003
    ..In vivo bioluminescence imaging provides a novel method to track the dynamics of engraftment of human HSC and progenitors in vivo...
  31. ncbi request reprint Advances in lentiviral vector design for gene-modification of hematopoietic stem cells
    Aaron C Logan
    Division of Research Immunology Bone Marrow Transplantation, Children s Hospital Los Angeles, 4650 Sunset Blvd, MS 62, Los Angeles, CA 90027, USA
    Curr Opin Biotechnol 13:429-36. 2002
    ....
  32. pmc Pre- and post-natal treatment of hemophagocytic lymphohistiocytosis
    Ami J Shah
    Division of Research Immunology, Childrens Hospital Los Angeles, California 90027, USA
    Pediatr Blood Cancer 52:139-42. 2009
    ..We report on the first patient to receive post-natal HSCT for HLH after receiving in utero chemotherapy for disease stabilization...
  33. ncbi request reprint Second hematopoietic stem cell transplantation in pediatric patients: overall survival and long-term follow-up
    Ami J Shah
    Division of Research Immunology Bone Marrow Transplantation, Childrens Hospital, Los Angeles, CA 90027, USA
    Biol Blood Marrow Transplant 8:221-8. 2002
    ..Although toxicity is considerable following a second transplantation, the major causes of mortality continue to be relapse and infection...
  34. ncbi request reprint Successful hematopoietic stem cell transplantation for Niemann-Pick disease type B
    Ami J Shah
    Division of Research Immunology Bone Marrow Transplantation, Childrens Hospital Los Angeles, CA 90027, USA
    Pediatrics 116:1022-5. 2005
    ..Five years after her second HSCT, her sphingomyelinase levels are within normal levels, she has no pulmonary symptoms, and aside from persistent graft versus host disease, she is doing well...
  35. doi request reprint Progressive declines in neurocognitive function among survivors of hematopoietic stem cell transplantation for pediatric hematologic malignancies
    Ami J Shah
    Department of Pediatrics, Division of Research Immunology Bone Marrow Transplantation, Childrens Hospital, Los Angeles, CA 90027, USA
    J Pediatr Hematol Oncol 30:411-8. 2008
    ..Although some patients have acute deficits that appear and improve over time, other patients have progressive declines in neurocognitive function that are chronic...
  36. doi request reprint Neurocognitive function of patients with severe combined immunodeficiency
    Ami J Shah
    Division of Research Immunology Bone Marrow Transplantation, Department of Pediatrics, The Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California Keck School of Medicine, 4650 Sunset Boulevard, MS 62, Los Angeles, CA 90027, USA
    Immunol Allergy Clin North Am 30:143-51. 2010
    ....
  37. ncbi request reprint Time course of bioluminescent signal in orthotopic and heterotopic brain tumors in nude mice
    J S Burgos
    Children s Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA
    Biotechniques 34:1184-8. 2003
    ..Future quantitative longitudinal studies must take into account the differences in the kinetics of different models...
  38. ncbi request reprint Lentiviral vector transduction of a dominant-negative Rev gene into human CD34+ hematopoietic progenitor cells potently inhibits human immunodeficiency virus-1 replication
    Ingrid Bahner
    Division of Research Immunology Bone Marrow Transplantation, The Saban Research Institute of Childrens Hospital Los Angeles, Los Angeles, California, USA
    Mol Ther 15:76-85. 2007
    ..These studies indicate that lentiviral vectors can be made effective for use in gene therapy for HIV-1...
  39. ncbi request reprint Effective suicide gene therapy for leukemia in a model of insertional oncogenesis in mice
    Martina Blumenthal
    Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, University of Los Angeles, California, USA
    Mol Ther 15:183-92. 2007
    ..Thus, in this model of vector-driven insertional oncogenesis, a suicide gene approach was effective for eliminating leukemia using modified HSV-TK variants with improved biological activity...
  40. pmc Update on gene therapy for immunodeficiencies
    Donald B Kohn
    Departments of Microbiology, Immunology and Immunology and Pediatrics, University of California, Los Angeles, 290D Biomedical Sciences Research Building, 615 Charles E Young Drive South, Los Angeles, CA 90095, USA
    Clin Immunol 135:247-54. 2010
    ..New approaches using safer integrating vectors or direct correction of the defective gene underlying the PID are being developed and may lead to safer and effective gene therapy for PID...
  41. doi request reprint Stable transgene expression in primitive human CD34+ hematopoietic stem/progenitor cells, using the Sleeping Beauty transposon system
    Teiko Sumiyoshi
    Division of Research Immunology Bone Marrow Transplantation, Saban Research Institute of Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA
    Hum Gene Ther 20:1607-26. 2009
    ....
  42. ncbi request reprint Neonatal gene therapy of MPS I mice by intravenous injection of a lentiviral vector
    Hiroshi Kobayashi
    Department of Pediatrics, Division of Research Immunology Bone Marrow Transplantation, The Saban Research Institute at Childrens Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA
    Mol Ther 11:776-89. 2005
    ..The sustained expression of enzymatically active IDUA in multiple organs had a significant beneficial effect on the phenotypic abnormalities of MPS I, which may be translated to clinical gene therapy of patients with Hurler disease...
  43. pmc The Moloney murine leukemia virus repressor binding site represses expression in murine and human hematopoietic stem cells
    Dennis L Haas
    Division of Research Immunology BMT, Children s Hospital Los Angeles, Los Angeles, California 90027, USA
    J Virol 77:9439-50. 2003
    ....
  44. ncbi request reprint Overexpression of tissue inhibitor of metalloproteinases-2 retroviral-mediated gene transfer in vivo inhibits tumor growth and invasion
    S Imren
    Division of Hematology Oncology, University of Southern California, Los Angeles 90027, USA
    Cancer Res 56:2891-5. 1996
    ....
  45. pmc Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo
    Nathalia Holt
    Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
    Nat Biotechnol 28:839-47. 2010
    ..The demonstration that a minority of CCR5(-/-) HSPCs can populate an infected animal with HIV-1-resistant, CCR5(-/-) progeny supports the use of ZFN-modified autologous hematopoietic stem cells as a clinical approach to treating HIV-1...
  46. pmc Expansion of multipotent and lymphoid-committed human progenitors through intracellular dimerization of Mpl
    Hisham Abdel-Azim
    Division of Research Immunology Bone Marrow Transplantation, Childrens Hospital Los Angeles, MS no 62, 4650 Sunset Blvd, Los Angeles, CA 90027, USA
    Blood 111:4064-74. 2008
    ..These data demonstrate that dimerization of a single cytokine receptor can deliver a profound expansion signal in both uncommitted and lymphoid-committed human hematopoietic progenitors...
  47. pmc Lentivirus vectors incorporating the immunoglobulin heavy chain enhancer and matrix attachment regions provide position-independent expression in B lymphocytes
    Carolyn Lutzko
    Division of Research Immunology and Bone Marrow Transplantation at Childrens Hospital Los Angeles, California 90027, USA
    J Virol 77:7341-51. 2003
    ..These vectors provide a useful tool for the study of B-lymphocyte biology and the development of gene therapy for disorders affecting B lymphocytes, such as immune deficiencies...
  48. ncbi request reprint Transduction of green fluorescent protein increased oxidative stress and enhanced sensitivity to cytotoxic drugs in neuroblastoma cell lines
    Hiroaki Goto
    Divisions of Hematology Oncology and Research Immunology Bone Marrow Transplantation, Childrens Hospital Los Angeles, CA 90027, USA
    Mol Cancer Ther 2:911-7. 2003
    ..Our data suggest caution when employing GFP-transduced cells to assess drug sensitivity and that using a cell surface antigen as a selection marker for gene transduction may perturb cells less than GFP...
  49. pmc Prolonged pancytopenia in a gene therapy patient with ADA-deficient SCID and trisomy 8 mosaicism: a case report
    Barbara C Engel
    Division of Research Immunology Bone Marrow Transplantation, General Clinical Research Center, Department of Pathology, Children s Hospital Los Angeles, CA 90027, and Baylor College of Medicine, Houston, TX, USA
    Blood 109:503-6. 2007
    ..The confounding effects of this preexisting marrow cytogenetic abnormality on the response to gene transfer highlights another challenge of gene therapy with the use of autologous hematopoietic stem cells...
  50. doi request reprint Clinical and genetic heterogeneity in Omenn syndrome and severe combined immune deficiency
    Tanja A Gruber
    Divisions of Hematology and Oncology, Children s Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027, USA
    Pediatr Transplant 13:244-50. 2009
    ..These cases highlight the clinical and genetic heterogeneity of OS...
  51. ncbi request reprint Factors influencing the titer and infectivity of lentiviral vectors
    Aaron C Logan
    Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
    Hum Gene Ther 15:976-88. 2004
    ..For the transduction of CD34+ HPCs, we found that the simplest method of increasing vector infectivity is to pseudotype vector particles with the RD114 envelope instead of vesicular stomatitis virus G glycoprotein (VSV-G)...
  52. ncbi request reprint Effects of busulfan dose escalation on engraftment of infant rhesus monkey hematopoietic stem cells after gene marking by a lentiviral vector
    Christoph A Kahl
    Division of Research Immunology Bone Marrow Transplantation, The Saban Research Institute of Childrens Hospital Los Angeles, CA 90027, USA
    Exp Hematol 34:369-81. 2006
    ..We utilized an infant rhesus monkey model to identify an optimal dosage of busulfan that results in efficient long-term gene marking with minimal toxicities...
  53. ncbi request reprint Specific and stable gene transfer to human embryonic stem cells using pseudotyped lentiviral vectors
    Jung Eun Jang
    Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA
    Stem Cells Dev 15:109-17. 2006
    ..These pseudotyped lentiviral vectors may be valuable tools for efficient, specific and stable gene modification of hESCs...
  54. ncbi request reprint Selective survival of peripheral blood lymphocytes in children with HIV-1 following delivery of an anti-HIV gene to bone marrow CD34(+) cells
    Greg M Podsakoff
    Childrens Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA
    Mol Ther 12:77-86. 2005
    ..These findings indicate that there was a selective survival advantage for PBMC containing the huM10 gene during the time of increased HIV-1 load...
  55. ncbi request reprint Long-term efficacy of enzyme replacement therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID)
    Belinda Chan
    Division of Research Immunology B M T, Mailstop number 62, Childrens Hospital Los Angeles, University of Southern California Keck School of Medicine, 4650 Sunset Blvd, Los Angeles, CA 90027, USA
    Clin Immunol 117:133-43. 2005
    ..These patients should be followed closely to detect a premature decline in immune function with aging in future decades of PEG-ADA therapy...
  56. ncbi request reprint Requirement for NK cells in CD40 ligand-mediated rejection of Philadelphia chromosome-positive acute lymphoblastic leukemia cells
    Tanja A Gruber
    Division of Research Immunology Bone Marrow Transplantation, Children s Hospital Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA 90027, USA
    J Immunol 168:73-80. 2002
    ..The ability of CD40L to act in a T cell-independent manner may be important for clinical applications in patients with depressed cellular immunity following chemotherapy...
  57. pmc Integrated self-inactivating lentiviral vectors produce full-length genomic transcripts competent for encapsidation and integration
    Aaron C Logan
    Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
    J Virol 78:8421-36. 2004
    ..Knowledge of the potential for mobilization of HIV-1-derived SIN lentivectors will be important for the design of future gene therapy trials with such vectors...
  58. pmc Regulated expansion of human pancreatic beta-cells
    Eszter Pais
    Division of Research Immunology Bone Marrow Transplantation, Department of Pediatrics, Childrens Hospital Los Angeles, Los Angeles, California, USA
    Mol Ther 18:1389-96. 2010
    ..In addition, specific proliferation of human pancreatic beta-cells was induced utilizing this approach. Selective, regulated beta-cell expansion may help to provide greater availability of cells for transplantation in patients with DM...
  59. ncbi request reprint The effects of Campath 1H upon graft-versus-host disease, infection, relapse, and immune reconstitution in recipients of pediatric unrelated transplants
    Ami J Shah
    Department of Pediatrics, Keck School of Medicine, Los Angeles, California, USA
    Biol Blood Marrow Transplant 13:584-93. 2007
    ..Further studies are warranted to assess if a lack of difference in infection rates are still demonstrated in larger cohorts...
  60. ncbi request reprint Preferential association of prostate cancer cells expressing prostate specific membrane antigen to bone marrow matrix
    Sonali P Barwe
    Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
    Int J Oncol 30:899-904. 2007
    ..This phenomenon occurs via activation of focal adhesion kinase and provides the first evidence of a link between PSMA expression and prostate cancer metastasis to the bone...
  61. ncbi request reprint Perspectives on gene therapy for immune deficiencies
    Greg M Podsakoff
    Division of Research Immunology, Bone Marrow Transplantation, Children s Hospital Los Angeles, Los Angeles, California 90027, USA
    Biol Blood Marrow Transplant 11:972-6. 2005
  62. ncbi request reprint Stable gene transfer to human CD34(+) hematopoietic cells using the Sleeping Beauty transposon
    Roger P Hollis
    Division of Research Immunology Bone Marrow Transplant, The Saban Research Institute of Childrens Hospital Los Angeles, Departments of Pediatrics, Los Angeles, CA 90027, USA
    Exp Hematol 34:1333-43. 2006
    ....
  63. ncbi request reprint Efficient characterization of retro-, lenti-, and foamyvector-transduced cell populations by high-accuracy insertion site sequencing
    Manfred Schmidt
    Department I of Internal Medicine, University of Freiburg, 79106 Freiburg, Germany
    Ann N Y Acad Sci 996:112-21. 2003
    ....
  64. pmc Redirecting specificity of T-cell populations for CD19 using the Sleeping Beauty system
    Harjeet Singh
    Division of Pediatrics, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Cancer Res 68:2961-71. 2008
    ..When coupled with numerical expansion on CD19(+) artificial antigen-presenting cells, this gene transfer method results in rapid outgrowth of CD4(+) and CD8(+) T cells expressing CAR to redirect specificity for CD19(+) tumor cells...
  65. doi request reprint Human hematopoietic cell culture, transduction, and analyses
    Jesper Bonde
    Statens Serum Institut, Copenhagen, Denmark
    Curr Protoc Hum Genet . 2008
    ..Other protocols provide PCR-based methods to analyze individual colonies for transduction, methods to analyze cells harvested from long-term cultures, and procedures for freezing and thawing of hematopoietic cells...
  66. ncbi request reprint Clonality analysis after retroviral-mediated gene transfer to CD34+ cells from the cord blood of ADA-deficient SCID neonates
    Manfred Schmidt
    Department I of Internal Medicine, University of Freiburg, Freiburg, Germany
    Nat Med 9:463-8. 2003
    ....
  67. ncbi request reprint Marrow-derived cells as vehicles for delivery of gene therapy to pulmonary epithelium
    Joanna E Grove
    Department of Laboratory Medicine, Yale University, New Haven, Connecticut, USA
    Am J Respir Cell Mol Biol 27:645-51. 2002
    ....
  68. ncbi request reprint Scaffold attachment region-containing retrovirus vectors improve long-term proviral expression after transplantation of GFP-modified CD34+ baboon repopulating cells
    Peter Kurre
    Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA
    Blood 102:3117-9. 2003
    ....
  69. ncbi request reprint Gene therapy of RAG-2-/- mice: sustained correction of the immunodeficiency
    Frank Yates
    Institut National de la Santé et de la Recherche Médicale INSERM U429, Hopital Necker Enfants Malades, Paris, France
    Blood 100:3942-9. 2002
    ..Altogether, this study demonstrates the efficiency of ex vivo RAG-2 gene transfer in HSCs to correct the immune deficiency of RAG-2-/- mice, constituting a significant step toward clinical application...
  70. ncbi request reprint Morphological analysis and lentiviral transduction of fetal monkey bone marrow-derived mesenchymal stem cells
    Chang I Lee
    California National Primate Research Center, University of California, Davis, California 95616 8542, USA
    Mol Ther 9:112-23. 2004
    ..that the SIN HIV-1-derived lentiviral vectors used in these studies can efficiently transduce rhMSC in vitro (CMV > EF1alpha > PGK) without inhibiting differentiation potential, although the cell cycle was transiently altered at high MOI..
  71. ncbi request reprint Fetal gene transfer using lentiviral vectors and the potential for germ cell transduction in rhesus monkeys (Macaca mulatta)
    C Chang I Lee
    California National Primate Research Center, University of California, Davis, CA 95616 8542, USA
    Hum Gene Ther 16:417-25. 2005
    ....
  72. pmc In vivo biosafety model to assess the risk of adverse events from retroviral and lentiviral vectors
    Gerhard Bauer
    Stem Cell Program, Department of Internal Medicine, University of California, Davis, Sacramento, California 95817, USA
    Mol Ther 16:1308-15. 2008
    ..Our in vivo system, therefore, helps to provide an assessment of the risks involved when retroviral or lentiviral vectors are considered for use in clinical gene therapy applications...
  73. ncbi request reprint Kinetics of fluorescence expression in nonhuman primates transplanted with GFP retrovirus-modified CD34 cells
    Peter Kurre
    Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, Washington 98109, USA
    Mol Ther 6:83-90. 2002
    ..In comparison to mouse studies, however, we did not detect substantial differences between MND and MoMuLV backbones...
  74. ncbi request reprint Effects of the negative control region on expression from retroviral LTR
    Lijun Wang
    Mol Ther 7:438-40. 2003
  75. pmc CD4+CD25- T cells transduced to express MHC class I-restricted epitope-specific TCR synthesize Th1 cytokines and exhibit MHC class I-restricted cytolytic effector function in a human melanoma model
    Arvind Chhabra
    Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA
    J Immunol 181:1063-70. 2008
    ..Such TCR engineered CD4(+) T cells, therefore, might be useful in clinical immunotherapy...
  76. ncbi request reprint Genetic therapies against HIV
    John J Rossi
    Division of Molecular Biology, Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, California 91010, USA
    Nat Biotechnol 25:1444-54. 2007
    ..The emergence of viral resistance can be addressed by therapies that use combinations of genetic agents and that inhibit both viral and host targets. Many of these strategies are being tested in ongoing and planned clinical trials...
  77. ncbi request reprint Letter to the editors of Nature from the American Society of Gene Therapy (ASGT) and the European Society of Gene Therapy (ESGT)
    Donald B Kohn
    J Gene Med 5:641. 2003
  78. ncbi request reprint Foamy virus vectors expressing anti-HIV transgenes efficiently block HIV-1 replication
    JASON A TAYLOR
    Department of Medicine, University of Washington, Seattle, Washington, USA
    Mol Ther 16:46-51. 2008
    ..These results suggest that there are potential benefits of using FV vectors in HIV gene therapy...
  79. ncbi request reprint Lentiviral vectors ready for prime-time
    Donald B Kohn
    Nat Biotechnol 25:65-6. 2007
  80. ncbi request reprint American Society of Gene Therapy (ASGT) ad hoc subcommittee on retroviral-mediated gene transfer to hematopoietic stem cells
    Donald B Kohn
    Mol Ther 8:180-7. 2003
  81. ncbi request reprint Simian immunodeficiency virus infection of hematopoietic stem cells and bone marrow stromal cells
    Chang I Lee
    California National Primate Research Center, University of California, Davis, CA 95616 8542, USA
    J Acquir Immune Defic Syndr 36:553-61. 2004
    ....
  82. ncbi request reprint Intrapulmonary and intramyocardial gene transfer in rhesus monkeys (Macaca mulatta): safety and efficiency of HIV-1-derived lentiviral vectors for fetal gene delivery
    Alice F Tarantal
    California National Primate Research Center, University of California, Davis, CA 95616, USA
    Mol Ther 12:87-98. 2005
    ....
  83. ncbi request reprint Recombinant murine interleukin-12 elicits potent antileukemic immune responses in a murine model of Philadelphia chromosome-positive acute lymphoblastic leukemia
    Tanja A Gruber
    Division of Research Immunology Bone Marrow Transplantation, Childrens Hospital Los Angeles 90027, USA
    Cancer Gene Ther 12:818-24. 2005
    ..These studies demonstrate the feasibility of an immunotherapeutic approach towards the treatment of Ph+ ALL...

Research Grants7

  1. GENE EXPRESSION IN BETA-CELLS BY LENTIVIRAL VECTORS
    Donald Kohn; Fiscal Year: 2003
    ..g. beta-cell precursors), or as reporter genes to indicate the transcriptional status of the insulin or PDX-1 genes, e.g. in response to glucose concentrations, hormones, growth factors, genes, or drugs. ..
  2. MND-ADA Transduced CD34 Cells for ADA-SCID
    Donald Kohn; Fiscal Year: 2005
    ..If sufficient gene-modified cells result, and PEG-ADA enzyme replacement therapy can be permanently discontinued, the advantage of this therapeutic approach may change the standard of care for these patients. ..
  3. Clinical Trial Planning Grant: Lentiviral Vector for HIV-1
    Donald Kohn; Fiscal Year: 2006
    ....
  4. In Vivo ADA Gene Delivery for the Treatment of SCID
    Donald Kohn; Fiscal Year: 2007
    ..Therefore, it is imperative to continue to develop new and improved methods to treat primary immune deficiency diseases and that is the primary goal of this project have significant efficacy, but remain sub-optimal. ..
  5. Conference--American Society of Gene Therapy
    Donald Kohn; Fiscal Year: 2007
    ..The annual ASGT meeting is the premier meeting in the field of gene therapy and serves as a rich source of information for the future generation of gene therapists. ..