A J Thrasher

Summary

Affiliation: University College London
Country: UK

Publications

  1. pmc Lentiviral vectors containing an enhancer-less ubiquitously acting chromatin opening element (UCOE) provide highly reproducible and stable transgene expression in hematopoietic cells
    Fang Zhang
    Centre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London, United Kingdom
    Blood 110:1448-57. 2007
  2. pmc Unregulated actin polymerization by WASp causes defects of mitosis and cytokinesis in X-linked neutropenia
    Dale A Moulding
    Wolfson Centre for Gene Therapy of Childhood Disease, UCL Institute of Child Health, University College London, London, UK
    J Exp Med 204:2213-24. 2007
  3. pmc The Wiskott-Aldrich syndrome: The actin cytoskeleton and immune cell function
    Michael P Blundell
    Molecular Immunology Unit, UCL Institute of Child Health, London, UK
    Dis Markers 29:157-75. 2010
  4. pmc Generation of functional neutrophils from a mouse model of X-linked chronic granulomatous disorder using induced pluripotent stem cells
    Sayandip Mukherjee
    Centre for Immunodeficiency, UCL Institute of Child Health, London, United Kingdom
    PLoS ONE 6:e17565. 2011
  5. pmc Wiskott-Aldrich Syndrome: Immunodeficiency resulting from defective cell migration and impaired immunostimulatory activation
    Gerben Bouma
    Centre for Immunodeficiency, UCL Institute of Child Health, London, UK
    Immunobiology 214:778-90. 2009
  6. ncbi request reprint Averting abnormal inheritance: potential of gene therapy and preimplantation diagnosis
    Adrian J Thrasher
    Consultant in Paediatric Immunology, Molecular Immunology Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
    Reprod Biomed Online 8:99-106. 2004
  7. ncbi request reprint Gene therapy for lympho-hematopoietic disorders
    Adrian J Thrasher
    Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
    Curr Hematol Rep 4:305-9. 2005
  8. ncbi request reprint Gene therapy in primary immunodeficiencies
    Adrian J Thrasher
    Molecular Immunology Unit, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK
    Expert Rev Clin Immunol 1:239-45. 2005
  9. ncbi request reprint WASp in immune-system organization and function
    Adrian J Thrasher
    Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
    Nat Rev Immunol 2:635-46. 2002
  10. doi request reprint Gene therapy for primary immunodeficiencies
    Adrian J Thrasher
    Centre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London and Great Ormond Street Hospital for Children NHS Trust, 30 Guilford Street, London WC1N 1EH, UK
    Immunol Allergy Clin North Am 28:457-71, xi. 2008

Collaborators

Detail Information

Publications117 found, 100 shown here

  1. pmc Lentiviral vectors containing an enhancer-less ubiquitously acting chromatin opening element (UCOE) provide highly reproducible and stable transgene expression in hematopoietic cells
    Fang Zhang
    Centre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London, United Kingdom
    Blood 110:1448-57. 2007
    ..These properties are achieved in the absence of classic enhancer activity and therefore may confer a high safety profile...
  2. pmc Unregulated actin polymerization by WASp causes defects of mitosis and cytokinesis in X-linked neutropenia
    Dale A Moulding
    Wolfson Centre for Gene Therapy of Childhood Disease, UCL Institute of Child Health, University College London, London, UK
    J Exp Med 204:2213-24. 2007
    ..These findings reveal a novel mechanism for inhibition of myelopoiesis through defective mitosis and cytokinesis due to hyperactivation and mislocalization of actin polymerization...
  3. pmc The Wiskott-Aldrich syndrome: The actin cytoskeleton and immune cell function
    Michael P Blundell
    Molecular Immunology Unit, UCL Institute of Child Health, London, UK
    Dis Markers 29:157-75. 2010
    ....
  4. pmc Generation of functional neutrophils from a mouse model of X-linked chronic granulomatous disorder using induced pluripotent stem cells
    Sayandip Mukherjee
    Centre for Immunodeficiency, UCL Institute of Child Health, London, United Kingdom
    PLoS ONE 6:e17565. 2011
    ....
  5. pmc Wiskott-Aldrich Syndrome: Immunodeficiency resulting from defective cell migration and impaired immunostimulatory activation
    Gerben Bouma
    Centre for Immunodeficiency, UCL Institute of Child Health, London, UK
    Immunobiology 214:778-90. 2009
    ....
  6. ncbi request reprint Averting abnormal inheritance: potential of gene therapy and preimplantation diagnosis
    Adrian J Thrasher
    Consultant in Paediatric Immunology, Molecular Immunology Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
    Reprod Biomed Online 8:99-106. 2004
    ..This paper discusses the finer details of these options, their safety and the ethical issues they have raised...
  7. ncbi request reprint Gene therapy for lympho-hematopoietic disorders
    Adrian J Thrasher
    Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
    Curr Hematol Rep 4:305-9. 2005
    ..Recently, several clinical studies have shown that conventional gene transfer technology can produce major beneficial therapeutic effects...
  8. ncbi request reprint Gene therapy in primary immunodeficiencies
    Adrian J Thrasher
    Molecular Immunology Unit, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK
    Expert Rev Clin Immunol 1:239-45. 2005
    ..New strategies to overcome these issues are likely to establish gene therapy as an efficacious strategy for many forms of primary immunodeficiencies...
  9. ncbi request reprint WASp in immune-system organization and function
    Adrian J Thrasher
    Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
    Nat Rev Immunol 2:635-46. 2002
    ..Now, WASp has been shown to be intimately involved in many pathways that influence the function of the immune system. Disturbances in these systems result in the complex immunodysregulation of Wiskott-Aldrich syndrome...
  10. doi request reprint Gene therapy for primary immunodeficiencies
    Adrian J Thrasher
    Centre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London and Great Ormond Street Hospital for Children NHS Trust, 30 Guilford Street, London WC1N 1EH, UK
    Immunol Allergy Clin North Am 28:457-71, xi. 2008
    ..Newer developments in vector design showing promise in overcoming these issues are likely to establish gene therapy as an efficacious strategy for many forms of primary immunodeficiencies...
  11. ncbi request reprint The Wiskott-Aldrich syndrome: disordered actin dynamics in haematopoietic cells
    A J Thrasher
    Molecular Immunology Unit, Institute of Child Health, University College London, England
    Immunol Rev 178:118-28. 2000
    ..This review discusses the evidence for regulation of highly dynamic cytoskeletal structures by WASp and the consequences of disturbed function on some of these processes...
  12. 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...
  13. ncbi request reprint Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy
    M Tschernutter
    Division of Molecular Therapy, Institute of Ophthalmology, University College London, UK
    Gene Ther 12:694-701. 2005
    ..This study demonstrates the potential of gene therapy approaches for the treatment of retinal degenerations caused by defects specific to the RPE and supports the use of lentiviral vectors for the treatment of such disorders...
  14. ncbi request reprint Kinetics of transgene expression in mouse retina following sub-retinal injection of recombinant adeno-associated virus
    G M Sarra
    Institute of Ophthalmology, University College London, 11 43 Bath Street, EC1V 9EL, London, UK
    Vision Res 42:541-9. 2002
    ..We failed to detect transfected cones even in areas where nearly 100% of the rods were transduced, but we found efficient and sustained RPE transduction...
  15. ncbi request reprint Intraocular gene delivery of ciliary neurotrophic factor results in significant loss of retinal function in normal mice and in the Prph2Rd2/Rd2 model of retinal degeneration
    F C Schlichtenbrede
    Department of Molecular Genetics, Institute of Ophthalmology, University College London, UK
    Gene Ther 10:523-7. 2003
    ..Our results demonstrate that intraocular CNTF gene delivery may have a deleterious effect on the retina and caution against its application in clinical trials...
  16. ncbi request reprint Improvement of neuronal visual responses in the superior colliculus in Prph2(Rd2/Rd2) mice following gene therapy
    F C Schlichtenbrede
    Department of Molecular Genetics, Institute of Ophthalmology, University College London, London EC1V 9EL, UK
    Mol Cell Neurosci 25:103-10. 2004
    ..These findings suggest that gene replacement therapy leading to even relatively modest structural improvement may result in improved central visual function...
  17. ncbi request reprint Gene replacement therapy in the retinal degeneration slow (rds) mouse: the effect on retinal degeneration following partial transduction of the retina
    G M Sarra
    Department of Molecular Genetics, Institute of Ophthalmology, University College London, Bath Street, London EC1V 9EL, UK
    Hum Mol Genet 10:2353-61. 2001
    ..These findings suggest that successful gene therapy in patients with photoreceptor defects may ultimately depend upon intervention in early stages of disease and upon accurate control of transgene expression...
  18. ncbi request reprint Stable rAAV-mediated transduction of rod and cone photoreceptors in the canine retina
    J W B Bainbridge
    Department of Molecular Genetics, Institute of Ophthalmology, University College London, London, UK
    Gene Ther 10:1336-44. 2003
    ..The possibility of adverse effects including intraocular immune responses and reduced retinal function requires further investigation prior to clinical applications in patients...
  19. ncbi request reprint In vivo gene transfer to the mouse eye using an HIV-based lentiviral vector; efficient long-term transduction of corneal endothelium and retinal pigment epithelium
    J W Bainbridge
    Institute of Ophthalmology, University College London, UK
    Gene Ther 8:1665-8. 2001
    ..Efficient in vivo gene transfer into cells of the corneal endothelium and retinal pigment epithelium by lentiviral vectors may therefore offer a valuable approach to the treatment of disorders of the cornea and outer retina...
  20. ncbi request reprint Wiskott-Aldrich syndrome: a disorder of haematopoietic cytoskeletal regulation
    A J Thrasher
    Molecular Immunology Unit, Institute of Child Health, London WC1N 1EH, United Kingdom
    Microsc Res Tech 47:107-13. 1999
    ....
  21. ncbi request reprint Hypoxia-regulated transgene expression in experimental retinal and choroidal neovascularization
    J W B Bainbridge
    Department of Molecular Genetics, Institute of Ophthalmology, University College London, 11 43 Bath Street, London EC1V 9EL, UK
    Gene Ther 10:1049-54. 2003
    ..HRE-driven gene expression offers an attractive strategy for the targeted and regulated delivery of angiostatic proteins to the retina in the management of neovascular disorders...
  22. ncbi request reprint High-level transduction and gene expression in hematopoietic repopulating cells using a human immunodeficiency [correction of imunodeficiency] virus type 1-based lentiviral vector containing an internal spleen focus forming virus promoter
    Christophe Demaison
    Molecular Immunology Unit, Institute of Child Health, UCL, 30 Guilford Street, London, WC1N 1EH, UK
    Hum Gene Ther 13:803-13. 2002
    ....
  23. ncbi request reprint Lentiviral transduction of the murine lung provides efficient pseudotype and developmental stage-dependent cell-specific transgene expression
    S M K Buckley
    Department of Haematology, Haemophilia Centre and Haemostasis Unit, Royal Free and University College Medical School, London, UK
    Gene Ther 15:1167-75. 2008
    ..This may provide a modality for treatment for lung disease in CF...
  24. ncbi request reprint Cell-specific and efficient expression in mouse and human B cells by a novel hybrid immunoglobulin promoter in a lentiviral vector
    K L Laurie
    Molecular Immunology Unit, Wolfson Centre for Gene Therapy of Childhood Disease, UCL Institute of Child Health, London, UK
    Gene Ther 14:1623-31. 2007
    ..These data demonstrate that in these conditions the Igk-E promoter is cell specific and controls efficient expression of a reporter protein in mouse and human B cells in the context of a lentiviral vector...
  25. ncbi request reprint Configuration of human dendritic cell cytoskeleton by Rho GTPases, the WAS protein, and differentiation
    S Burns
    Molecular Immunology Unit, Institute of Child Health, University College London, United Kingdom
    Blood 98:1142-9. 2001
    ..Formation of podosomes is restricted to cells with an immature phenotype, indicating a specific role for these structures during the early migratory phase. (Blood. 2001;98:1142-1149)..
  26. ncbi request reprint Detailed characterization of the human aorta-gonad-mesonephros region reveals morphological polarity resembling a hematopoietic stromal layer
    C J Marshall
    Molecular Immunology Unit, Institute of Child Health, London, England
    Dev Dyn 215:139-47. 1999
    ..This region of cells may therefore provide the microenvironmental support for the intraembryonic development of definitive hematopoietic stem cells, a process in which tenascin-C may play a pivotal role...
  27. ncbi request reprint A defined window for efficient gene marking of severe combined immunodeficient-repopulating cells using a gibbon ape leukemia virus-pseudotyped retroviral vector
    C Demaison
    Molecular Immunology Unit, Institute of Child Health, London, United Kingdom
    Hum Gene Ther 11:91-100. 2000
    ..This adds to the emerging evidence of heterogeneity within the SRC compartment, and has important implications for the interpretation of this assay in stem cell transplantation and gene transfer studies...
  28. doi request reprint Progress and prospects: gene therapy for inherited immunodeficiencies
    W Qasim
    Molecular Immunology Unit, UCL Institute of Child Health, London, UK
    Gene Ther 16:1285-91. 2009
    ..A new generation of self-inactivating retroviral and lentiviral vectors have been designed to address these safety concerns, and are at an advanced stage of preparation for the next phase of clinical testing...
  29. ncbi request reprint Cutting edge: the Wiskott-Aldrich syndrome protein is required for efficient phagocytosis of apoptotic cells
    Y Leverrier
    Ludwig Institute for Cancer Research, Royal Free and University College Medical School Branch, London, United Kingdom
    J Immunol 166:4831-4. 2001
    ..The efficiency of apoptotic cell clearance may be a key determinant in the suppression of tissue inflammation and prevention of autoimmunity...
  30. doi request reprint Efficient gene delivery to the adult and fetal CNS using pseudotyped non-integrating lentiviral vectors
    A A Rahim
    Perinatal Brain Protection and Repair Group, Department of Obstetrics and Gynaecology, University College London, London, UK
    Gene Ther 16:509-20. 2009
    ....
  31. ncbi request reprint Wiskott-Aldrich syndrome protein is necessary for efficient IgG-mediated phagocytosis
    R Lorenzi
    Department of Molecular Immunology, Institute of Child Health, London, England
    Blood 95:2943-6. 2000
    ..Results also show that, in normal macrophages, WASp itself is actively recruited to the cup, suggesting that assembly of this specialized cytoskeletal structure is dependent on its expression. (Blood. 2000;95:2943-2946)..
  32. ncbi request reprint Inhibition of retinal neovascularisation by gene transfer of soluble VEGF receptor sFlt-1
    J W B Bainbridge
    Department of Molecular Genetics, Institute of Ophthalmology, University College London, London, UK
    Gene Ther 9:320-6. 2002
    ..05). Local gene transfer of sFlt-1 consistently inhibits experimental retinal neovascularisation by approximately 50% and offers a powerful novel approach to the clinical management of retinal neovascular disorders...
  33. ncbi request reprint Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector
    H Bobby Gaspar
    Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Lancet 364:2181-7. 2004
    ..We investigated the application of somatic gene therapy by use of a gibbon-ape-leukaemia-virus pseudotyped gammaretroviral vector...
  34. pmc Immunotherapy for neuroblastoma using syngeneic fibroblasts transfected with IL-2 and IL-12
    S E Barker
    Molecular Immunology Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
    Br J Cancer 97:210-7. 2007
    ..Furthermore, as they are easier to recover and manipulate than autologous tumour cells, fibroblasts provide an attractive alternative immunotherapeutic strategy for the treatment of neuroblastoma...
  35. ncbi request reprint Protein assays for diagnosis of Wiskott-Aldrich syndrome and X-linked thrombocytopenia
    W Qasim
    Molecular Immunology Unit, Institute of Child Health, University College London, UK
    Br J Haematol 113:861-5. 2001
    ..In all cases, subsequent genetic analysis confirmed the presence of a WASp gene mutation. We believe that protein-based assays should be employed as the first line of investigation in the diagnosis of WAS spectrum disorders...
  36. ncbi request reprint Murine leukemia following irradiation conditioning for transplantation of lentivirally-modified hematopoietic stem cells
    Elena K Siapati
    Hematopoietic Stem Cell Laboratory, Cancer Research UK, London, UK
    Eur J Haematol 78:303-13. 2007
    ....
  37. ncbi request reprint Current progress on gene therapy for primary immunodeficiencies
    L Zhang
    Molecular Immunology Unit, Center for Immunodeficiency, Institute of Child Health, University College London, London, UK
    Gene Ther 20:963-9. 2013
    ..If long-term efficacy and safety are shown, gene therapy will become a standard treatment option for specific forms of PID. ..
  38. ncbi request reprint Gene therapy progress and prospects: gene therapy for severe combined immunodeficiency
    H B Gaspar
    Molecular Immunology Unit, Institute of Child Health, London, UK
    Gene Ther 10:1999-2004. 2003
    ....
  39. ncbi request reprint Gene therapy of inherited immunodeficiencies
    Giorgia Santilli
    University College London, Institute of Child Health, Centre for Immunodeficiency, Molecular Immunology Unit, 30 Guilford Street, London, WC1N 1EH, UK
    Expert Opin Biol Ther 8:397-407. 2008
    ..In severe cases allogeneic haematopoietic stem cell transplantation has proved to be a successful curative modality but it is limited by toxicity and reduced efficacy in mismatched donor settings...
  40. ncbi request reprint Long-term evaluation of retinal function in Prph2Rd2/Rd2 mice following AAV-mediated gene replacement therapy
    Frank C Schlichtenbrede
    Department of Molecular Genetics, Institute of Ophthalmology, University College London, UK
    J Gene Med 5:757-64. 2003
    ..Here we quantify the functional rescue over a 15-week time course and present a detailed analysis of the improvement in retinal function...
  41. ncbi request reprint Impaired dendritic-cell homing in vivo in the absence of Wiskott-Aldrich syndrome protein
    Sofia de Noronha
    Molecular Immunology Unit, Institute of Child Health, London WC1N 1EH, UK
    Blood 105:1590-7. 2005
    ....
  42. ncbi request reprint Lack of T-cell responses following autologous tumour lysate pulsed dendritic cell vaccination, in patients with relapsed osteosarcoma
    N Himoudi
    Unit of Molecular Haematology and Cancer Biology, University College London Institute of Child Health, London, UK
    Clin Transl Oncol 14:271-9. 2012
    ..We therefore conducted a phase I trial to assess feasibility, safety and tumour-specific immune responses in patients with relapsed disease...
  43. ncbi request reprint Dendritic cells: the bare bones of immunity
    S Burns
    Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
    Curr Biol 14:R965-7. 2004
    ..Dendritic cells are specialized antigen-presenting cells, critical for initiating and regulating immune responses. Two new studies demonstrate the importance of coordinated cytoskeletal regulation for their normal function...
  44. ncbi 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
    ....
  45. ncbi request reprint Improvement of migratory defects in a murine model of Wiskott-Aldrich syndrome gene therapy
    Michael P Blundell
    Molecular Immunology Unit, Wolfson Centre for Gene Therapy of Childhood Disease, University College London Institute of Child Health, London, UK
    Mol Ther 16:836-44. 2008
    ....
  46. ncbi request reprint Effective gene therapy with nonintegrating lentiviral vectors
    Rafael J Yáñez-Muñoz
    Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
    Nat Med 12:348-53. 2006
    ..For therapeutic application to postmitotic tissues, this system substantially reduces the risk of insertional mutagenesis...
  47. ncbi request reprint T cell transduction and suicide with an enhanced mutant thymidine kinase
    W Qasim
    Molecular Immunology Unit, Institute of Child Health, University College London, UK
    Gene Ther 9:824-7. 2002
    ..The less toxic agent aciclovir also eliminated T cells transduced with HSV-TKSR39 (but not HSV-TK), underlining the increased therapeutic potential of the mutant suicide gene system in the bone marrow transplantation setting...
  48. ncbi request reprint T cell suicide gene therapy to aid haematopoietic stem cell transplantation
    W Qasim
    Molecular Immunology Unit, Institute of Child Health, 30, Guilford Street, London WC1N 1EH, UK
    Curr Gene Ther 5:121-32. 2005
    ..Efforts are now directed towards circumventing the pre-activation requirements of retroviral vectors by using alternative lentiviral systems, in association with improved suicide gene/prodrug combinations...
  49. ncbi request reprint Genetic variants associated with neutrophil function in aggressive periodontitis and healthy controls
    L Nibali
    Periodontology Unit and Division of Clinical Research University College London, Eastman Dental Institute London, UK
    J Periodontol 81:527-34. 2010
    ..The aim of this study is to test whether a clinical diagnosis and specific genetic variants are associated with neutrophil activity in subjects with AgP and healthy subjects...
  50. ncbi request reprint Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning
    H Bobby Gaspar
    Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
    Mol Ther 14:505-13. 2006
    ..No serious side effects were seen either as a result of the conditioning procedure or due to retroviral insertion. Gene therapy is an effective treatment option for the treatment of ADA-SCID...
  51. pmc Update on clinical gene therapy in childhood
    Waseem Qasim
    Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Arch Dis Child 92:1028-31. 2007
    ..Minimising such risks through improved vector design will play an important role in developing the next generation of gene based therapies and extending their applicability...
  52. ncbi request reprint CD34 stem cell top-ups without conditioning after initial haematopoietic stem cell transplantation for correction of incomplete haematopoietic and immunological recovery in severe congenital immunodeficiencies
    Claire Booth
    Department of Clinical Immunology, Great Ormond Street Hospital NHS Trust, London, UK
    Br J Haematol 135:533-7. 2006
    ..Unconditioned stem cell boosts have limited toxicity but should be given early after the original graft to be effective...
  53. ncbi request reprint Fetal haemopoietic cells display enhanced migration across endothelium
    Kwee L Yong
    Department of Haematology, University College London, UK
    Br J Haematol 116:392-400. 2002
    ..The superior migratory activity of fetal haemopoietic cells may underlie a more efficient homing ability, in keeping with their physiological role...
  54. ncbi request reprint Lentiviral vectors for T-cell suicide gene therapy: preservation of T-cell effector function after cytokine-mediated transduction
    Waseem Qasim
    Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Mol Ther 15:355-60. 2007
    ..We conclude that the use of interleukin-7 for lentiviral transduction offers the greatest potential for gene transfer to T cells without loss of function, and is favored for the clinical production of suicide gene modified T cells...
  55. ncbi request reprint Mechanisms of WASp-mediated hematologic and immunologic disease
    Siobhan Burns
    Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford St, London, WC1N 1EH, United Kingdom
    Blood 104:3454-62. 2004
    ..This review highlights recent advances that have enhanced our understanding of the mechanisms by which these molecular defects cause hematologic and immunologic disease...
  56. doi request reprint Effect of gene therapy on visual function in Leber's congenital amaurosis
    James W B Bainbridge
    Institute of Ophthalmology, University College London, London, United Kingdom
    N Engl J Med 358:2231-9. 2008
    ..These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747 [ClinicalTrials.gov].)...
  57. pmc A congenital activating mutant of WASp causes altered plasma membrane topography and adhesion under flow in lymphocytes
    Siobhan O Burns
    Molecular Immunology Unit, Centre for Immunodeficiency, Institute of Child Health, University College London, London, UK
    Blood 115:5355-65. 2010
    ..Together, our results demonstrate that WASp(I294T) significantly affects lymphocyte membrane topography and L-selectin-dependent adhesion, which may be linked to defective hematopoiesis and leukocyte function in affected patients...
  58. pmc Hybrid lentiviral vectors
    Waseem Qasim
    Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Mol Ther 18:1263-7. 2010
    ..Here, we review recent progress in the development of such hybrid lentiviral systems and consider potential applications of such vectors...
  59. pmc Phosphorylation of WASp is a key regulator of activity and stability in vivo
    Michael P Blundell
    Molecular Immunology Unit, Wolfson Centre for Gene Therapy of Childhood Disease and Centre for Immunodeficiency, UCL Institute of Child Health, London, WC1N 1EH, United Kingdom
    Proc Natl Acad Sci U S A 106:15738-43. 2009
    ..Furthermore, it may target WASp for proteasome-mediated degradation, thereby providing a default mechanism for self-limiting stimulation of the Arp2/3 complex...
  60. ncbi request reprint Maturation of DC is associated with changes in motile characteristics and adherence
    Siobhan Burns
    Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London, United Kingdom
    Cell Motil Cytoskeleton 57:118-32. 2004
    ..The temporal regulation of podosome assembly during DC maturation also suggests that they may be most critical for early movement, perhaps during transmigration of lymphatic endothelium...
  61. ncbi request reprint Gene therapy for severe combined immune deficiency
    Waseem Qasim
    Molecular Immunology Unit, Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK
    Expert Rev Mol Med 6:1-15. 2004
    ....
  62. ncbi request reprint The impact of retroviral suicide gene transduction procedures on T cells
    Waseem Qasim
    Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Br J Haematol 123:712-9. 2003
    ..These observations may explain the lower than expected levels of GVHD and poor antiviral immunity reported in recent trials...
  63. ncbi request reprint AAV-Mediated gene transfer slows photoreceptor loss in the RCS rat model of retinitis pigmentosa
    Alexander J Smith
    Molecular Genetics, Institute of Ophthalmology, London, United Kingdom
    Mol Ther 8:188-95. 2003
    ..5-fold higher in treated than in control eyes. This study provides strong support for the development of AAV-mediated gene therapy for RP caused by mutations in the MERTK gene...
  64. ncbi request reprint Gene therapy for inherited immunodeficiencies
    Steven Howe
    Molecular Immunology Unit, Institute of Child Health, 30 Guilford Street, London WCIN 1EH, UK
    Curr Hematol Rep 2:328-34. 2003
    ..This review examines the progress and the problems that have arisen, and discusses the improvement and future of gene therapy for primary immunodeficiencies...
  65. ncbi request reprint Failure of SCID-X1 gene therapy in older patients
    Adrian J Thrasher
    Molecular Immunology Unit, Institute of Child Health, London, United Kingdom
    Blood 105:4255-7. 2005
    ..In particular, there is likely to be a limitation to initiation of normal thymopoiesis, and we therefore suggest that intervention for these patients should be considered as early as possible...
  66. ncbi request reprint Local administration of an adeno-associated viral vector expressing IL-10 reduces monocyte infiltration and subsequent photoreceptor damage during experimental autoimmune uveitis
    Cathryn A Broderick
    Division of Molecular Therapy, Institute of Ophthalmology, University College, London, 11 43 Bath Street, London EC1V 9EL, UK
    Mol Ther 12:369-73. 2005
    ....
  67. ncbi request reprint Gene therapy for ocular angiogenesis
    James W B Bainbridge
    Department of Molecular Genetics, Institute of Ophthalmology, University College London, 11 43 Bath Street, London EC1V 9EL, U K
    Clin Sci (Lond) 104:561-75. 2003
    ..Recent progress has enabled the planning of clinical trials of gene therapy for ocular neovascular disorders...
  68. ncbi request reprint Diminished production of anti-inflammatory mediators during neutrophil apoptosis and macrophage phagocytosis in chronic granulomatous disease (CGD)
    Joanne R Brown
    Immunobiology Unit, The Institute of Child Health, Great Ormond Street Hospital, University College London, United Kingdom
    J Leukoc Biol 73:591-9. 2003
    ....
  69. ncbi request reprint Long-term reversal of chronic anemia using a hypoxia-regulated erythropoietin gene therapy
    Katie Binley
    Oxford BioMedica UK Ltd Molecular Immunology Unit, Institute of Child Health, London, United Kingdom
    Blood 100:2406-13. 2002
    ..We envisage that this control system will allow regulated delivery of therapeutic gene products in other ischemic settings...
  70. ncbi request reprint Gene therapy for severe combined immunodeficiencies
    H Bobby Gaspar
    Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK
    Expert Opin Biol Ther 5:1175-82. 2005
    ..These side effects are now being studied in detail and measures to prevent such events through alternative vectors delivery systems are in development at present...
  71. pmc Improved antitumour immunity in murine neuroblastoma using a combination of IL-2 and IL-12
    K E Siapati
    Molecular Immunology Unit, Institute of Child Health, London, UK
    Br J Cancer 88:1641-8. 2003
    ..These results suggest that IL-2 and IL-12, when cotransfected in tumour cells, are effective against established disease and provide a promising immunotherapeutic approach for the treatment of neuroblastoma...
  72. ncbi request reprint Restoration of photoreceptor ultrastructure and function in retinal degeneration slow mice by gene therapy
    R R Ali
    Department of Molecular Genetics, Institute of Ophthalmology, University College London, UK
    Nat Genet 25:306-10. 2000
    ..These studies demonstrate for the first time that a complex ultrastructural cell defect can be corrected both morphologically and functionally by in vivo gene transfer...
  73. ncbi request reprint Polarized expression of bone morphogenetic protein-4 in the human aorta-gonad-mesonephros region
    C J Marshall
    Molecular Immunology Unit, Institute of Child Health, London, UK
    Blood 96:1591-3. 2000
    ..Furthermore, the distribution of BMP-4 expression is highly suggestive of a direct role in the specification of human hematopoietic cells from embryonic mesoderm in vivo. (Blood. 2000;96:1591-1593)..
  74. ncbi request reprint Stable gene transfer to muscle using non-integrating lentiviral vectors
    Luis Apolonia
    Molecular Immunology Unit, Institute of Child Health, London, UK
    Mol Ther 15:1947-54. 2007
    ..Finally, we show that NILV can be used for achieving highly effective gene transfer and expression in muscle in vivo...
  75. ncbi request reprint Cognitive and behavioral abnormalities in children after hematopoietic stem cell transplantation for severe congenital immunodeficiencies
    Penny Titman
    Department of Psychosocial Services, Great Ormond Street Hospital National Health Service NHS Trust, London, UK
    Blood 112:3907-13. 2008
    ..The specific genetic diagnosis, consanguinity, and severe clinical course are associated with poor outcome. Long-term follow-up of these patients should include screening to identify and manage these problems more effectively...
  76. ncbi request reprint Enhancement of integrin-mediated transfection of haematopoietic cells with a synthetic vector system
    Aima Uduehi
    Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
    Biotechnol Appl Biochem 38:201-9. 2003
    ..The LID vector may thus find application for gene-transfer experiments in haematopoietic cell lines and for the development of genetic vaccines using transfected dendritic cells...
  77. pmc The Wiskott-Aldrich syndrome
    A J Thrasher
    Molecular Immunology Unit, Institute of Child Health, London, UK
    Clin Exp Immunol 120:2-9. 2000
  78. ncbi request reprint Essential role of the NADPH oxidase subunit p47(phox) in endothelial cell superoxide production in response to phorbol ester and tumor necrosis factor-alpha
    Jian Mei Li
    Department of Cardiology, Guy s King s and St Thomas School of Medicine Denmark Hill Campus, King s College London, London, UK
    Circ Res 90:143-50. 2002
    ..These data show that endothelial cell p47(phox) is critical in the upregulation of NADPH oxidase activity by PMA and TNFalpha...
  79. ncbi request reprint High-titer stocks of adeno-associated virus from replicating amplicons and herpes vectors
    Ajay R Mistry
    Molecular Immunology Unit, Institute of Child Health, Institute of Ophthalmology, London, United Kingdom
    Methods Mol Med 69:445-60. 2002
  80. ncbi request reprint Impaired T-cell priming in vivo resulting from dysfunction of WASp-deficient dendritic cells
    Gerben Bouma
    Institute of Child Health, University College London UCL, Molecular Immunology Unit, London, UK
    Blood 110:4278-84. 2007
    ....
  81. pmc Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients
    Steven J Howe
    Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, University College London, London, United Kingdom
    J Clin Invest 118:3143-50. 2008
    ....
  82. pmc Nonintegrating lentivector vaccines stimulate prolonged T-cell and antibody responses and are effective in tumor therapy
    Katarzyna Karwacz
    Division of Infection and Immunity, University College London, London, United Kingdom
    J Virol 83:3094-103. 2009
    ..In this case, both the vector genome and the immune response were maintained for at least 2 months. Together, our data indicate that nonintegrating lentivectors can be employed to generate effective vaccines...
  83. ncbi request reprint Use of nonintegrating lentiviral vectors for gene therapy
    Nicola J Philpott
    Molecular Immunology Unit, Institute of Child Health, University College London, London WC1N 1EH, United Kingdom
    Hum Gene Ther 18:483-9. 2007
    ..We also discuss their potential application to gene therapy and the treatment of genetic disease...
  84. ncbi request reprint Rituximab for the treatment of autoimmune cytopenias in children with immune deficiency
    J J Kim
    Department of Immunology, Great Ormond Street Hospital, London, UK
    Br J Haematol 138:94-6. 2007
    ..We conclude that rituximab is an effective treatment for autoimmune cytopenias in children with immune deficiencies, but repeated courses of treatment may be needed...
  85. ncbi request reprint Enhanced human cell engraftment in mice deficient in RAG2 and the common cytokine receptor gamma chain
    J P Goldman
    Molecular Immunology Unit, Institute of Child Health, London, UK
    Br J Haematol 103:335-42. 1998
    ....
  86. pmc Translational mini-review series on immunodeficiency: molecular defects in common variable immunodeficiency
    C Bacchelli
    Molecular Immunology Unit, Institute of Child Health, London, UK
    Clin Exp Immunol 149:401-9. 2007
    ..Together these defects account for perhaps 10-15% of all cases of CVID and it is highly likely that further genetic defects will be identified...
  87. pmc Neonatal dendritic cells are intrinsically biased against Th-1 immune responses
    C L Langrish
    Molecular Immunology Unit, University College London, UK
    Clin Exp Immunol 128:118-23. 2002
    ..The reduced ability of cord DCs to attain a fully mature adult phenotype, and to activate naive CD4+ T cells to produce IFN-gamma, suggests that they are intrinsically preprogrammed against the generation of Th-1 immune responses...
  88. pmc A ubiquitous chromatin opening element (UCOE) confers resistance to DNA methylation-mediated silencing of lentiviral vectors
    Fang Zhang
    Centre for Immunodeficiency, Molecular Immunology Unit, Institute of Child Health, University College London, London, UK
    Mol Ther 18:1640-9. 2010
    ..The A2UCOE therefore has considerable utility for gene therapy applications where reliable and sustained gene expression is desirable...
  89. ncbi request reprint Human gamma delta T cells: a lymphoid lineage cell capable of professional phagocytosis
    Yin Wu
    Molecular Immunology Unit, University College London Institute of Child Health, London, U K
    J Immunol 183:5622-9. 2009
    ....
  90. pmc Sleeping beauty transposition from nonintegrating lentivirus
    Conrad A Vink
    Institute of Child Health, University College London, UK
    Mol Ther 17:1197-204. 2009
    ..Importantly, integration site analysis revealed redirection toward a profile mimicking SB-plasmid integration and away from integration within transcriptionally active genes favored by integrase-proficient lentiviral vectors (ILVs)...
  91. ncbi request reprint Bone marrow-derived IFN-producing killer dendritic cells account for the tumoricidal activity of unpulsed dendritic cells
    Nourredine Himoudi
    Unit of Molecular Haematology and Cancer Biology, Institute of Child Health, London, United Kingdom
    J Immunol 181:6654-63. 2008
    ..Our data suggest that bone marrow-derived IKDC represent a population that has powerful tumoricidal activity in vivo...
  92. ncbi request reprint Development of anti-PAX3 immune responses; a target for cancer immunotherapy
    Nourredine Himoudi
    Unit of Molecular Haematology and Cancer Biology, Institute of Child Health, London, WC1N 1EH, UK
    Cancer Immunol Immunother 56:1381-95. 2007
    ..The ability to generate strong and specific anti PAX3 immune responses from the T cell repertoire in both mice and humans, provides evidence for PAX3 as a promising target for immunotherapy of cancer...
  93. pmc Bone morphogenetic protein 4 modulates c-Kit expression and differentiation potential in murine embryonic aorta-gonad-mesonephros haematopoiesis in vitro
    Caroline J Marshall
    Molecular Immunology Unit, UCL Institute of Child Health, London, UK
    Br J Haematol 139:321-30. 2007
    ....
  94. ncbi request reprint SAP mediates specific cytotoxic T-cell functions in X-linked lymphoproliferative disease
    Reza Sharifi
    Molecular Immunology Unit, Institute of Child Health, University College London, London, United Kingdom
    Blood 103:3821-7. 2004
    ..These studies demonstrate that in XLP the lack of SAP affects specific signaling pathways resulting in severe disruption of CTL function...
  95. pmc Update on the hyper immunoglobulin M syndromes
    E Graham Davies
    Centre for Immunodeficiency, Institute of Child Health, London, UK
    Br J Haematol 149:167-80. 2010
    ..Those with a defective CSR mechanism generally do well on immunoglobulin replacement therapy. Complications may include autoimmunity, lymphoid hyperplasia and, in some cases, a predisposition to lymphoid malignancy...
  96. ncbi request reprint WASP: a key immunological multitasker
    Adrian J Thrasher
    Molecular Immunology Unit and Centre for Immunodeficiency, University College London Institute of Child Health, London, UK
    Nat Rev Immunol 10:182-92. 2010
    ..Here, we describe recent insights into the cellular mechanisms of these two related, but distinct, human diseases and discuss their wider implications for haematopoiesis, immune function and autoimmunity...
  97. ncbi request reprint Autoimmune lymphoproliferative syndrome: molecular basis of disease and clinical phenotype
    Austen Worth
    Department of Clinical Immunology, Great Ormond Street Hospital NHS Trust, London, UK
    Br J Haematol 133:124-40. 2006
    ..This review provides a detailed insight into the pathophysiology of lymphocyte apoptosis and how this relates to the variable and complex clinical manifestations of ALPS...
  98. ncbi request reprint RISC control for gene therapy
    Waseem Qasim
    Nat Biotechnol 24:661-2. 2006
  99. ncbi request reprint Oncogenesis following delivery of a nonprimate lentiviral gene therapy vector to fetal and neonatal mice
    Mike Themis
    Gene Therapy Research Group, Section of Cell and Molecular Biology, Imperial College London, UK
    Mol Ther 12:763-71. 2005
    ..This system may provide a highly sensitive model to investigate integrating vector safety prior to clinical application...
  100. ncbi request reprint Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy
    Salima Hacein-Bey-Abina
    Laboratoire INSERM, Hopital Necker Enfants Malades, Paris, France
    N Engl J Med 346:1185-93. 2002
    ..We investigated whether infusion of autologous hematopoietic stem cells that had been transduced in vitro with the gamma(c) gene can restore the immune system in patients with severe combined immunodeficiency...
  101. ncbi request reprint Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1
    Marion G Ott
    Department of Hematology Oncology, University Hospital, German Cancer Research Center, Theodor Stern Kai 7, 60590 Frankfurt, Germany
    Nat Med 12:401-9. 2006
    ....