Virus-mediated gene delivery for human gene therapy.

After over 20 years from the first application of gene transfer in humans, gene therapy is now a mature discipline, which has progressively overcome several of the hurdles that prevented clinical success in the early stages of application. So far, the vast majority of gene therapy clinical trials have exploited viral vectors as very efficient nucleic acid delivery vehicles both in vivo and ex vivo. Here we summarize the current status of viral gene transfer for clinical applications, with special emphasis on the molecular properties of the major classes of viral vectors and the information so far obtained from gene therapy clinical trials.

[1]  R. Samulski,et al.  Infectious Entry Pathway of Adeno-Associated Virus and Adeno-Associated Virus Vectors , 2000, Journal of Virology.

[2]  M. Kay,et al.  Correction of hemophilia B in canine and murine models using recombinant adeno-associated viral vectors , 1999, Nature Medicine.

[3]  T. VandenDriessche,et al.  Clinical gene transfer studies for hemophilia A. , 2004, Seminars in thrombosis and hemostasis.

[4]  A. Fattaey,et al.  An Adenovirus Mutant That Replicates Selectively in p53- Deficient Human Tumor Cells , 1996, Science.

[5]  H. Kaufman,et al.  OPTIM trial: a Phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma. , 2010, Future oncology.

[6]  J. Schlehofer,et al.  Update on the prevalence of serum antibodies (IgG and IgM) to adeno‐associated virus (AAV) , 1999, Journal of medical virology.

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

[8]  N. Brunetti‐Pierri,et al.  Progress and prospects: gene therapy for genetic diseases with helper-dependent adenoviral vectors , 2008, Gene Therapy.

[9]  Christof von Kalle,et al.  Stem-cell gene therapy for the Wiskott-Aldrich syndrome. , 2010, The New England journal of medicine.

[10]  W. Russell,et al.  Adenoviruses: update on structure and function. , 2009, The Journal of general virology.

[11]  L. Naldini,et al.  Lentiviral vectors containing the human immunodeficiency virus type-1 central polypurine tract can efficiently transduce nondividing hepatocytes and antigen-presenting cells in vivo. , 2002, Blood.

[12]  F. Gage,et al.  In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector , 1996, Science.

[13]  E. Galanis,et al.  Clinical trial results with oncolytic virotherapy: a century of promise, a decade of progress , 2007, Nature Clinical Practice Oncology.

[14]  Keyun Qing,et al.  Adeno-associated virus 2 co-receptors?-first reply , 1999, Nature Medicine.

[15]  M. Weitzman,et al.  Processing of recombinant AAV genomes occurs in specific nuclear structures that overlap with foci of DNA-damage-response proteins , 2008, Journal of Cell Science.

[16]  R. Kotin,et al.  Adeno-associated virus type 5: transduction efficiency and cell-type specificity in the primate retina. , 2003, Human gene therapy.

[17]  M. Gulley,et al.  A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[18]  Luca Biasco,et al.  Multilineage hematopoietic reconstitution without clonal selection in ADA-SCID patients treated with stem cell gene therapy. , 2007, The Journal of clinical investigation.

[19]  J. Burns,et al.  Generation of high-titer pseudotyped retroviral vectors with very broad host range. , 1994, Methods in cell biology.

[20]  J. Agudo,et al.  In vivo genetic engineering of murine pancreatic beta cells mediated by single-stranded adeno-associated viral vectors of serotypes 6, 8 and 9 , 2011, Diabetologia.

[21]  R. Kotin,et al.  Cloning of adeno-associated virus type 4 (AAV4) and generation of recombinant AAV4 particles , 1997, Journal of virology.

[22]  A. Epstein Progress and prospects: Biological properties and technological advances of herpes simplex virus type 1-based amplicon vectors , 2009, Gene Therapy.

[23]  N. Mazarakis,et al.  Enhanced pseudotyping efficiency of HIV-1 lentiviral vectors by a rabies/vesicular stomatitis virus chimeric envelope glycoprotein , 2011, Gene Therapy.

[24]  K. High,et al.  Immune responses to AAV in clinical trials. , 2007, Current gene therapy.

[25]  A. Epstein,et al.  HSV as a vector in vaccine development and gene therapy. , 2008, Advances in experimental medicine and biology.

[26]  M. Imperiale,et al.  Production of first generation adenovirus vectors: a review , 2000, Gene Therapy.

[27]  R. Samulski,et al.  αVβ5 integrin: a co-receptor for adeno-associated virus type 2 infection , 1999, Nature Medicine.

[28]  M. Yudkoff,et al.  Recombinant adenovirus gene transfer in adults with partial ornithine transcarbamylase deficiency (OTCD). , 1999, Human gene therapy.

[29]  Alessandro Aiuti,et al.  Hot spots of retroviral integration in human CD34+ hematopoietic cells. , 2007, Blood.

[30]  A. Epstein,et al.  Efficient and non-toxic gene transfer to cardiomyocytes using novel generation amplicon vectors derived from HSV-1. , 2005, Journal of molecular and cellular cardiology.

[31]  J. Petrini,et al.  Rad50 Is Dispensable for the Maintenance and Viability of Postmitotic Tissues , 2008, Molecular and Cellular Biology.

[32]  Alessandro Guffanti,et al.  High-definition mapping of retroviral integration sites identifies active regulatory elements in human multipotent hematopoietic progenitors. , 2010, Blood.

[33]  D. Muruve,et al.  The innate immune response to adenovirus vectors. , 2004, Human gene therapy.

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

[35]  M. Hallek,et al.  AAV-based gene transfer. , 2003, Current opinion in molecular therapeutics.

[36]  A. Miller,et al.  Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection , 1990, Molecular and cellular biology.

[37]  Theresa A. Storm,et al.  Robust systemic transduction with AAV9 vectors in mice: efficient global cardiac gene transfer superior to that of AAV8. , 2006, Molecular therapy : the journal of the American Society of Gene Therapy.

[38]  Kazuto Kobayashi,et al.  Neuron-specific gene transfer through retrograde transport of lentiviral vector pseudotyped with a novel type of fusion envelope glycoprotein. , 2011, Human gene therapy.

[39]  R. Samulski,et al.  Cross-Dressing the Virion: the Transcapsidation of Adeno-Associated Virus Serotypes Functionally Defines Subgroups , 2004, Journal of Virology.

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

[41]  Yan Cui,et al.  Lentiviral vectors with CMV or MHCII promoters administered in vivo: immune reactivity versus persistence of expression. , 2007, Molecular therapy : the journal of the American Society of Gene Therapy.

[42]  C. Kao,et al.  Gene Therapy for Prostate Cancer by Controlling Adenovirus E1a and E4 Gene Expression with PSES Enhancer , 2005 .

[43]  J. Pessin,et al.  Dynamin Is Required for Recombinant Adeno-Associated Virus Type 2 Infection , 1999, Journal of Virology.

[44]  R. Friedman Expression of human adenosine deaminase using a transmissable murine retrovirus vector system. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[45]  M. Weitzman,et al.  Transduction with recombinant adeno-associated virus for gene therapy is limited by leading-strand synthesis , 1996, Journal of virology.

[46]  R. Daniel,et al.  Integration site selection by retroviral vectors: molecular mechanism and clinical consequences. , 2008, Human gene therapy.

[47]  Youichi Suzuki,et al.  The road to chromatin — nuclear entry of retroviruses , 2007, Nature Reviews Microbiology.

[48]  Qiang Liu,et al.  Molecular basis of the inflammatory response to adenovirus vectors , 2003, Gene Therapy.

[49]  S. Snyder,et al.  Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization , 1999, Nature Medicine.

[50]  B. Hub,et al.  Endocytosis of Adeno-Associated Virus Type 5 Leads to Accumulation of Virus Particles in the Golgi Compartment , 2002, Journal of Virology.

[51]  K. High,et al.  AAV-mediated gene transfer for the treatment of hemophilia B: problems and prospects , 2008, Gene Therapy.

[52]  D. Sze,et al.  Phase I/II study of oncolytic herpes simplex virus NV1020 in patients with extensively pretreated refractory colorectal cancer metastatic to the liver. , 2010, Human gene therapy.

[53]  U. Dietrich,et al.  Pseudotyping Vesicular Stomatitis Virus with Lymphocytic Choriomeningitis Virus Glycoproteins Enhances Infectivity for Glioma Cells and Minimizes Neurotropism , 2011, Journal of Virology.

[54]  M. Chillón,et al.  Gutless adenovirus: last-generation adenovirus for gene therapy , 2005, Gene Therapy.

[55]  M. Kay,et al.  The 37/67-Kilodalton Laminin Receptor Is a Receptor for Adeno-Associated Virus Serotypes 8, 2, 3, and 9 , 2006, Journal of Virology.

[56]  D. Descamps,et al.  Two key challenges for effective adenovirus-mediated liver gene therapy: innate immune responses and hepatocyte-specific transduction. , 2009, Current gene therapy.

[57]  M. Giacca,et al.  Integration site selection by retroviruses. , 2004, AIDS reviews.

[58]  J. Simons,et al.  Prostate attenuated replication competent adenovirus (ARCA) CN706: a selective cytotoxic for prostate-specific antigen-positive prostate cancer cells. , 1997, Cancer research.

[59]  H. Yang,et al.  Dendritic cell-directed lentivector vaccine induces antigen-specific immune responses against murine melanoma , 2011, Cancer Gene Therapy.

[60]  D. Kirn,et al.  Gene therapy progress and prospects cancer: oncolytic viruses , 2008, Gene Therapy.

[61]  M. Sadelain,et al.  The genetic engineering of hematopoietic stem cells: the rise of lentiviral vectors, the conundrum of the ltr, and the promise of lineage-restricted vectors. , 2007, Molecular therapy : the journal of the American Society of Gene Therapy.

[62]  P. Kaleebu,et al.  Adenovirus-Based Vaccines: Comparison of Vectors from Three Species of Adenoviridae , 2010, Journal of Virology.

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

[64]  H. Wakimoto,et al.  Oncolytic herpes simplex virus vectors and chemotherapy: are combinatorial strategies more effective for cancer? , 2010, Future oncology.

[65]  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.

[66]  R. Ali,et al.  Success in sight: The eyes have it! Ocular gene therapy trials for LCA look promising , 2008, Gene Therapy.

[67]  R. Linden,et al.  Adeno-associated virus site-specifically integrates into a muscle-specific DNA region. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[68]  J. Glorioso,et al.  Herpes vector-mediated gene transfer in treatment of diseases of the nervous system. , 2004, Annual review of microbiology.

[69]  Macgregor Rr Clinical protocol. A phase 1 open-label clinical trial of the safety and tolerability of single escalating doses of autologous CD4 T cells transduced with VRX496 in HIV-positive subjects. , 2001 .

[70]  L. Zentilin,et al.  Involvement of Cellular Double-Stranded DNA Break Binding Proteins in Processing of the Recombinant Adeno-Associated Virus Genome , 2001, Journal of Virology.

[71]  Gianluigi Zanetti,et al.  Lentiviral vector common integration sites in preclinical models and a clinical trial reflect a benign integration bias and not oncogenic selection. , 2011, Blood.

[72]  J. Couzin-Frankel Genetics. The promise of a cure: 20 years and counting. , 2009, Science.

[73]  Roberto Cattaneo,et al.  Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded , 2008, Nature Reviews Microbiology.

[74]  K. Nakano,et al.  HSV trafficking and development of gene therapy vectors with applications in the nervous system , 2005, Gene Therapy.

[75]  E. Lehtonen,et al.  Evaluation of risks related to the use of adeno-associated virus-based vectors. , 2003, Current gene therapy.

[76]  G. Trobridge Genotoxicity of retroviral hematopoietic stem cell gene therapy , 2011, Expert opinion on biological therapy.

[77]  T. Samulski,et al.  Second-strand synthesis is a rate-limiting step for efficient transduction by recombinant adeno-associated virus vectors , 1996, Journal of virology.

[78]  A. Schambach,et al.  Clinical application of lentiviral vectors - concepts and practice. , 2008, Current gene therapy.

[79]  B. Davidson,et al.  What does it take to bind CAR? , 2005, Molecular therapy : the journal of the American Society of Gene Therapy.

[80]  J. Cody,et al.  Armed replicating adenoviruses for cancer virotherapy , 2009, Cancer Gene Therapy.

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

[82]  J. Kornegay,et al.  Widespread muscle expression of an AAV9 human mini-dystrophin vector after intravenous injection in neonatal dystrophin-deficient dogs. , 2010, Molecular therapy : the journal of the American Society of Gene Therapy.

[83]  Y. Chérel,et al.  Recombinant adeno-associated virus serotype 4 mediates unique and exclusive long-term transduction of retinal pigmented epithelium in rat, dog, and nonhuman primate after subretinal delivery. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[84]  Pin Wang,et al.  Pseudotyping lentiviral vectors with aura virus envelope glycoproteins for DC-SIGN-mediated transduction of dendritic cells. , 2011, Human gene therapy.

[85]  R. Linden,et al.  The cryptic life style of adenoassociated virus , 1995, BioEssays : news and reviews in molecular, cellular and developmental biology.

[86]  N. Bessis,et al.  Immune responses to gene therapy vectors: influence on vector function and effector mechanisms , 2004, Gene therapy.

[87]  J. Glorioso,et al.  Replication-defective genomic HSV gene therapy vectors: design, production and CNS applications. , 2005, Current opinion in molecular therapeutics.

[88]  R. Ali,et al.  AAV-mediated gene therapy for retinal disorders: from mouse to man , 2008, Gene Therapy.

[89]  S. Bhide,et al.  Phase I/II Study of Oncolytic HSVGM-CSF in Combination with Radiotherapy and Cisplatin in Untreated Stage III/IV Squamous Cell Cancer of the Head and Neck , 2010, Clinical Cancer Research.

[90]  C. Aiken Pseudotyping human immunodeficiency virus type 1 (HIV-1) by the glycoprotein of vesicular stomatitis virus targets HIV-1 entry to an endocytic pathway and suppresses both the requirement for Nef and the sensitivity to cyclosporin A , 1997, Journal of virology.

[91]  A. Miller Retrovirus packaging cells. , 1990, Human gene therapy.

[92]  R. Kotin,et al.  Characterization of a preferred site on human chromosome 19q for integration of adeno‐associated virus DNA by non‐homologous recombination. , 1992, The EMBO journal.

[93]  R. Samulski,et al.  Adeno-associated virus serotypes: vector toolkit for human gene therapy. , 2006, Molecular therapy : the journal of the American Society of Gene Therapy.

[94]  T. Rabbitts,et al.  Activation of the T-cell oncogene LMO2 after gene therapy for X-linked severe combined immunodeficiency. , 2004, The New England journal of medicine.

[95]  D. Nettelbeck,et al.  Novel oncolytic adenoviruses targeted to melanoma: specific viral replication and cytolysis by expression of E1A mutants from the tyrosinase enhancer/promoter. , 2002, Cancer research.

[96]  I. Tannock,et al.  A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer , 2000, Nature Medicine.

[97]  Hoguen Kim,et al.  Ad-mTERT-delta19, a conditional replication-competent adenovirus driven by the human telomerase promoter, selectively replicates in and elicits cytopathic effect in a cancer cell-specific manner. , 2003, Human gene therapy.

[98]  W. Yung,et al.  Δ24-hyCD adenovirus suppresses glioma growth in vivo by combining oncolysis and chemosensitization , 2005, Cancer Gene Therapy.

[99]  M. Gulley,et al.  Erratum: A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer (Clinical Cancer Research (2000) 6 (798-806)) , 2000 .

[100]  A. Epstein,et al.  HSV-1-derived helper-independent defective vectors, replicating vectors and amplicon vectors, for the treatment of brain diseases. , 2010, Current opinion in drug discovery & development.

[101]  J. Huard,et al.  Gene transfer to skeletal muscle using herpes simplex virus-based vectors. , 2004, Methods in molecular biology.

[102]  Lung-Ji Chang,et al.  Efficient and persistent transduction of exocrine and endocrine pancreas by adeno-associated virus type 8. , 2007, Journal of biomedical science.

[103]  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.

[104]  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.

[105]  S. W. Kim,et al.  Evolution of oncolytic adenovirus for cancer treatment. , 2012, Advanced drug delivery reviews.

[106]  R. H. Smith,et al.  Adeno-associated virus integration: virus versus vector , 2008, Gene Therapy.

[107]  D. Grimm,et al.  Novel tools for production and purification of recombinant adenoassociated virus vectors. , 1998, Human gene therapy.

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

[109]  R. Samulski,et al.  Self-complementary AAV mediates gene targeting and enhances endonuclease delivery for double-strand break repair , 2010, Gene Therapy.

[110]  P. Sinn,et al.  Gene Therapy Progress and Prospects: Development of improved lentiviral and retroviral vectors – design, biosafety, and production , 2005, Gene Therapy.

[111]  Theresa A. Storm,et al.  The host response to adenovirus, helper-dependent adenovirus, and adeno-associated virus in mouse liver. , 2008, Molecular therapy : the journal of the American Society of Gene Therapy.

[112]  O. Merten,et al.  Adeno-associated viruses. , 2011, Methods in molecular biology.

[113]  Sally Lehrman,et al.  Virus treatment questioned after gene therapy death , 1999, Nature.

[114]  Alan McClelland,et al.  Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector , 2000, Nature Genetics.

[115]  W. Xiao,et al.  Characterization of Tissue Tropism Determinants of Adeno-Associated Virus Type 1 , 2003, Journal of Virology.

[116]  D. Trono,et al.  Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery , 1998, Journal of Virology.

[117]  M. Finer,et al.  Second–generation adenovirus vectors , 1996, Nature Medicine.

[118]  Edward B. Miller,et al.  α2,3 and α2,6 N-Linked Sialic Acids Facilitate Efficient Binding and Transduction by Adeno-Associated Virus Types 1 and 6 , 2006, Journal of Virology.

[119]  Heartening results: the CUPID gene therapy trial for heart failure. , 2011, Molecular therapy : the journal of the American Society of Gene Therapy.

[120]  N. Copeland,et al.  Gene Therapy Insertional Mutagenesis Insights , 2004, Science.

[121]  M. Sadelain,et al.  Occurrence of leukaemia following gene therapy of X-linked SCID , 2003, Nature Reviews Cancer.

[122]  D. Mccarty Self-complementary AAV vectors; advances and applications. , 2008, Molecular therapy : the journal of the American Society of Gene Therapy.

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

[124]  M. Rudnicki,et al.  A helper-dependent adenovirus vector system: removal of helper virus by Cre-mediated excision of the viral packaging signal. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[125]  Alan McClelland,et al.  AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. , 2003, Blood.

[126]  R. Buckley Gene therapy for SCID—a complication after remarkable progress , 2002, The Lancet.

[127]  B. Levine,et al.  Regulatory considerations for novel gene therapy products: a review of the process leading to the first clinical lentiviral vector. , 2005, Human gene therapy.

[128]  S. Bernasconi,et al.  A human immunodeficiency virus type 1 pol gene-derived sequence (cPPT/CTS) increases the efficiency of transduction of human nondividing monocytes and T lymphocytes by lentiviral vectors. , 2002, Human gene therapy.

[129]  K. Propert,et al.  Immune responses to adenovirus and adeno-associated virus in humans , 1999, Gene Therapy.

[130]  A. Epstein,et al.  HSV-1-derived recombinant and amplicon vectors for gene transfer and gene therapy. , 2005, Current gene therapy.

[131]  R. Manservigi,et al.  Replication-competent herpes simplex vectors: design and applications , 2005, Gene Therapy.

[132]  R. Linden,et al.  The recombination signals for adeno-associated virus site-specific integration. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[133]  L. Zentilin,et al.  Adeno-associated virus vectors: versatile tools for in vivo gene transfer. , 2008, Contributions to nephrology.

[134]  M. Simonatto,et al.  DNA damage and cellular differentiation: More questions than responses , 2007, Journal of cellular physiology.