Gene therapy clinical trials worldwide to 2012 – an update

To date, over 1800 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical trials from official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors.

[1]  A. Fischer,et al.  Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. , 2002, The New England journal of medicine.

[2]  L. Notarangelo,et al.  How I treat ADA deficiency. , 2009, Blood.

[3]  Marius Wernig,et al.  Treatment of Sickle Cell Anemia Mouse Model with iPS Cells Generated from Autologous Skin , 2007, Science.

[4]  F. Muntoni,et al.  Personalized exon skipping strategies to address clustered non-deletion dystrophin mutations , 2010, Neuromuscular Disorders.

[5]  D. Kuhns,et al.  Retrovirus gene therapy for X-linked chronic granulomatous disease can achieve stable long-term correction of oxidase activity in peripheral blood neutrophils. , 2010, Blood.

[6]  R. Herzog.  Gene therapy for SCID-X1: round 2. , 2010, Molecular therapy : the journal of the American Society of Gene Therapy.

[7]  D. Silbergeld,et al.  Extended Survival of Glioblastoma Patients After Chemoprotective HSC Gene Therapy , 2012, Science Translational Medicine.

[8]  C. von Kalle,et al.  Retroviral gene therapy for X-linked chronic granulomatous disease: results from phase I/II trial. , 2008, Molecular therapy : the journal of the American Society of Gene Therapy.

[9]  Cameron S. Osborne,et al.  LMO2-Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1 , 2003, Science.

[10]  Christine Kinnon,et al.  Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. , 2008, The Journal of clinical investigation.

[11]  F. Bushman,et al.  Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. , 2008, The Journal of clinical investigation.

[12]  S. Woo,et al.  Complete and persistent phenotypic correction of phenylketonuria in mice by site-specific genome integration of murine phenylalanine hydroxylase cDNA , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[13]  M. Raffeld,et al.  Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  Wenbo Zhou,et al.  Adenoviral Gene Delivery Can Reprogram Human Fibroblasts to Induced Pluripotent Stem Cells , 2009, Stem cells.

[15]  Alexander Sumaroka,et al.  Vision 1 year after gene therapy for Leber's congenital amaurosis. , 2009, The New England journal of medicine.

[16]  Abdul Hakkim,et al.  Restoration of NET formation by gene therapy in CGD controls aspergillosis. , 2009, Blood.

[17]  M. Oshimura,et al.  Complete Genetic Correction of iPS Cells From Duchenne Muscular Dystrophy , 2009, Molecular therapy : the journal of the American Society of Gene Therapy.

[18]  S. Rosenberg,et al.  T Lymphocyte-Directed Gene Therapy for ADA− SCID: Initial Trial Results After 4 Years , 1995, Science.

[19]  R. Stewart,et al.  Human Induced Pluripotent Stem Cells Free of Vector and Transgene Sequences , 2009, Science.

[20]  Roland W Herzog,et al.  Evading the immune response upon in vivo gene therapy with viral vectors. , 2009, Current opinion in molecular therapeutics.

[21]  Alessandro Aiuti,et al.  Gene therapy for immunodeficiency due to adenosine deaminase deficiency. , 2009, The New England journal of medicine.

[22]  A. Fischer,et al.  Treatment of an infant with X-linked severe combined immunodeficiency ( SCID-X 1 ) by gene therapy in Australia , 2000 .

[23]  H. Gaspar.  Bone marrow transplantation and alternatives for adenosine deaminase deficiency. , 2010, Immunology and allergy clinics of North America.

[24]  Edwin M Stone,et al.  Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics , 2008, Proceedings of the National Academy of Sciences.

[25]  K. Cichutek,et al.  Is it going to be SIN? , 2006, The journal of gene medicine.

[26]  Kathryn L. Parsley,et al.  Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning. , 2006, Molecular therapy : the journal of the American Society of Gene Therapy.

[27]  J. Wixon,et al.  Gene therapy clinical trials worldwide 1989–2004—an overview , 2004, The journal of gene medicine.

[28]  B. Smart.  Stem-Cell Gene Therapy for the Wiskott-Aldrich Syndrome , 2011, Pediatrics.

[29]  F. Deist,et al.  Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. , 2000, Science.

[30]  Etiena Basner-Tschakarjan,et al.  AAV-1-mediated gene transfer to skeletal muscle in humans results in dose-dependent activation of capsid-specific T cells. , 2009, Blood.

[31]  S. Yamanaka,et al.  Induction of pluripotent stem cells from fibroblast cultures , 2007, Nature Protocols.

[32]  D. Persons,et al.  Solving the problem of γ-retroviral vectors containing long terminal repeats. , 2011, Molecular therapy : the journal of the American Society of Gene Therapy.

[33]  M. Dinauer,et al.  Gene therapy of chronic granulomatous disease: the engraftment dilemma. , 2011, Molecular therapy : the journal of the American Society of Gene Therapy.

[34]  M. Hoggan.  Adenovirus associated viruses. , 1970, Progress in medical virology. Fortschritte der medizinischen Virusforschung. Progres en virologie medicale.

[35]  Kathleen A. Marshall,et al.  Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial , 2009, The Lancet.

[36]  Jérôme Larghero,et al.  Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia , 2010, Nature.

[37]  A. Fire,et al.  Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans , 1998, Nature.

[38]  One of three successfully treated CGD patients in a Swiss‐German gene therapy trial died due to his underlying disease , 2006, The journal of gene medicine.

[39]  A. Consiglio,et al.  Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells , 2009, Nature.

[40]  Hans Martin,et al.  Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease , 2010, Nature Medicine.

[41]  L. Notarangelo,et al.  Immune reconstitution in ADA-SCID after PBL gene therapy and discontinuation of enzyme replacement , 2002, Nature Medicine.

[42]  David L. Porter,et al.  T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia , 2011, Science Translational Medicine.

[43]  S. Yamanaka,et al.  Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors , 2006, Cell.

[44]  Kathryn L. Parsley,et al.  Biochemical correction of X-CGD by a novel chimeric promoter regulating high levels of transgene expression in myeloid cells. , 2011, Molecular therapy : the journal of the American Society of Gene Therapy.

[45]  Robert Lanza,et al.  Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. , 2009, Cell stem cell.

[46]  R. Jaenisch,et al.  Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease , 2008, Proceedings of the National Academy of Sciences.

[47]  Kathleen A. Marshall,et al.  AAV2 Gene Therapy Readministration in Three Adults with Congenital Blindness , 2012, Science Translational Medicine.

[48]  W. Hauswirth,et al.  Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. , 2008, Human gene therapy.

[49]  A. Bagg,et al.  Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. , 2011, The New England journal of medicine.

[50]  M. Kay,et al.  Early Clinical Trial Results Following Administration of a Low Dose of a Novel Self Complementary Adeno-Associated Viral Vector Encoding Human Factor IX In Two Subjects with Severe Hemophilia B , 2010 .

[51]  Nick Tyler,et al.  Effect of gene therapy on visual function in Leber's congenital amaurosis. , 2008, The New England journal of medicine.

[52]  Alexander Meissner,et al.  Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. , 2010, Cell stem cell.

[53]  S. Rosenberg,et al.  Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes , 2006, Science.

[54]  K. Weinberg,et al.  Prolonged pancytopenia in a gene therapy patient with ADA-deficient SCID and trisomy 8 mosaicism: a case report. , 2007, Blood.

[55]  J. Bourke,et al.  Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study , 2011, The Lancet.

[56]  B. Coiffier,et al.  Final Results From a Pivotal, Multicenter, International, Open-Label, Phase 2 Study of Romidepsin In Progressive or Relapsed Peripheral T-Cell Lymphoma (PTCL) Following Prior Systemic Therapy , 2010 .

[57]  A. Annoni,et al.  A microRNA-regulated lentiviral vector mediates stable correction of hemophilia B mice. , 2007, Blood.

[58]  E. Simons.  Gene Therapy of X-Linked Severe Combined Immunodeficiency by Use of a Pseudotyped Gammaretroviral Vector , 2006, Pediatrics.

[59]  Frederic D. Bushman,et al.  Efficacy of gene therapy for X-linked severe combined immunodeficiency. , 2010, The New England journal of medicine.

[60]  Christof von Kalle,et al.  A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. , 2003, The New England journal of medicine.

[61]  Zhao-hui Peng,et al.  Current status of gendicine in China: recombinant human Ad-p53 agent for treatment of cancers. , 2005, Human gene therapy.

[62]  Yang Du,et al.  Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1 , 2006, Nature Medicine.

[63]  I. Graham,et al.  Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study , 2009, The Lancet Neurology.

[64]  E Marshall,et al.  Gene Therapy Death Prompts Review of Adenovirus Vector , 1999, Science.

[65]  C. Kesserwan,et al.  Recent advances in gene therapy for severe congenital immunodeficiency diseases , 2008, Current opinion in hematology.

[66]  Johan T den Dunnen,et al.  Standard mutation nomenclature in molecular diagnostics: practical and educational challenges. , 2007, The Journal of molecular diagnostics : JMD.

[67]  S. Cole,et al.  Sequences Human Induced Pluripotent Stem Cells Free of Vector and Transgene , 2012 .

[68]  R. Stewart,et al.  Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells , 2007, Science.

[69]  A. Mortellaro,et al.  Correction of ADA-SCID by Stem Cell Gene Therapy Combined with Nonmyeloablative Conditioning , 2002, Science.

[70]  K. Cornetta,et al.  Gene transfer into humans--immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction. , 1990, The New England journal of medicine.

[71]  L. Naldini,et al.  Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer , 2006, Nature Medicine.

[72]  Anastasia Khvorova,et al.  Induction of the interferon response by siRNA is cell type- and duplex length-dependent. , 2006, RNA.

[73]  M. Hasegawa,et al.  Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome , 2009, Proceedings of the Japan Academy. Series B, Physical and biological sciences.

[74]  J. Kaiser,et al.  As Gelsinger Case Ends, Gene Therapy Suffers Another Blow , 2005, Science.

[75]  A. Aiuti,et al.  Update on gene therapy for adenosine deaminase-deficient severe combined immunodeficiency , 2010, Current opinion in allergy and clinical immunology.

[76]  Jerry M. Guo,et al.  Splicing Out the West? , 2006, Science.

[77]  Donald B Kohn,et al.  Update on gene therapy for immunodeficiencies. , 2010, Clinical immunology.

[78]  B. Gansbacher.  Policy statement on the social, ethical and public awareness issues in gene therapy. , 2002 .

[79]  A. Annoni,et al.  In vivo delivery of a microRNA-regulated transgene induces antigen-specific regulatory T cells and promotes immunologic tolerance. , 2009, Blood.

[80]  B. Gansbacher.  Report of a second serious adverse event in a clinical trial of gene therapy for X‐linked severe combined immune deficiency (X‐SCID) , 2003, The journal of gene medicine.

[81]  J. Rasko,et al.  Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response , 2006, Nature Medicine.

[82]  A. Hotz-Wagenblatt,et al.  Insertion of retroviral vectors in NOD/SCID repopulating human peripheral blood progenitor cells occurs preferentially in the vicinity of transcription start regions and in introns. , 2004, Molecular therapy : the journal of the American Society of Gene Therapy.

[83]  Jo Wixon,et al.  Gene therapy clinical trials worldwide to 2007—an update , 2007, The journal of gene medicine.

[84]  Christine Kinnon,et al.  Mutations in TNFRSF13B Encoding TACI Are Associated With Common Variable Immunodeficiency in Humans , 2006, Pediatrics.

[85]  A. Fischer,et al.  Lentiviral hematopoietic cell gene therapy for X-linked adrenoleukodystrophy. , 2012, Methods in Enzymology.

[86]  Jean Bennett,et al.  Gene Therapy for Leber's Congenital Amaurosis is Safe and Effective Through 1.5 Years After Vector Administration , 2009, Molecular therapy : the journal of the American Society of Gene Therapy.

[87]  Pratima Chowdary,et al.  Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. , 2011, The New England journal of medicine.

[88]  Manfred Schmidt,et al.  Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy , 2009, Science.

[89]  Adam Bagg,et al.  Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. , 2003, Molecular genetics and metabolism.