Intrathymic adeno-associated virus gene transfer rapidly restores thymic function and long-term persistence of gene-corrected T cells

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Intrathymic adeno-associated virus gene transfer rapidly restores thymic function and long-term persistence of gene-corrected T cells Marie Pouzolles, Alice Machado, Mickaël Guilbaud, Magali Irla, Sarah Gailhac, Pierre Barennes, Daniela Cesana, Andrea Calabria, Fabrizio Benedicenti, Arnauld Sergé, et al.

[1]  J. Puck,et al.  Lentiviral Gene Therapy Combined with Low‐Dose Busulfan in Infants with SCID‐X1 , 2019, The New England journal of medicine.

[2]  Neel H. Shah,et al.  ZAP-70 in Signaling, Biology, and Disease. , 2018, Annual review of immunology.

[3]  B. Wilhelm,et al.  Humoral Immune Response After Intravitreal But Not After Subretinal AAV8 in Primates and Patients. , 2018, Investigative ophthalmology & visual science.

[4]  L. Notarangelo,et al.  Efficacy of lentivirus‐mediated gene therapy in an Omenn syndrome recombination‐activating gene 2 mouse model is not hindered by inflammation and immune dysregulation , 2017, The Journal of allergy and clinical immunology.

[5]  B. Wilhelm,et al.  AAV8 Can Induce Innate and Adaptive Immune Response in the Primate Eye. , 2017, Molecular therapy : the journal of the American Society of Gene Therapy.

[6]  G. Ronzitti,et al.  Emerging Issues in AAV-Mediated In Vivo Gene Therapy , 2017, Molecular therapy. Methods & clinical development.

[7]  F. Mingozzi,et al.  Unraveling the Complex Story of Immune Responses to AAV Vectors Trial After Trial , 2017, Human gene therapy.

[8]  A. Singer,et al.  Identification of lineage-specifying cytokines that signal all CD8-cytotoxic lineage fate decisions in the thymus , 2017, Nature Immunology.

[9]  R. Jenq,et al.  Loss of thymic innate lymphoid cells leads to impaired thymopoiesis in experimental graft-versus-host disease. , 2017, Blood.

[10]  Thomas Voit,et al.  Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy , 2017, Nature Communications.

[11]  Nolan J Brown,et al.  Adeno-Associated Virus Vectors and Stem Cells: Friends or Foes? , 2017, Human gene therapy.

[12]  R. Grange,et al.  Long‐term effects of systemic gene therapy in a canine model of myotubular myopathy , 2017, Muscle & nerve.

[13]  Jason S. Mitchell,et al.  T cell progenitor therapy-facilitated thymopoiesis depends upon thymic input and continued thymic microenvironment interaction. , 2017, JCI insight.

[14]  M. V. D. van den Brink,et al.  Intrathymic injection of hematopoietic progenitor cells establishes functional T cell development in a mouse model of severe combined immunodeficiency , 2017, Journal of Hematology & Oncology.

[15]  Yasmine El-Shamayleh,et al.  AAV-mediated delivery of optogenetic constructs to the macaque brain triggers humoral immune responses. , 2017, Journal of neurophysiology.

[16]  Barbara Engel,et al.  Clinical efficacy of gene-modified stem cells in adenosine deaminase–deficient immunodeficiency , 2017, The Journal of clinical investigation.

[17]  M. Irla,et al.  Administration of RANKL boosts thymic regeneration upon bone marrow transplantation , 2017, EMBO molecular medicine.

[18]  L. Naldini,et al.  Gene therapy for ADA‐SCID, the first marketing approval of an ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products , 2017, EMBO molecular medicine.

[19]  R. Grange,et al.  Systemic AAV8-Mediated Gene Therapy Drives Whole-Body Correction of Myotubular Myopathy in Dogs. , 2017, Molecular therapy : the journal of the American Society of Gene Therapy.

[20]  R. Chandler,et al.  Recombinant Adeno-Associated Viral Integration and Genotoxicity: Insights from Animal Models. , 2017, Human gene therapy.

[21]  James M. Wilson,et al.  Regulatory and Exhausted T Cell Responses to AAV Capsid. , 2017, Human gene therapy.

[22]  L. Notarangelo,et al.  Current Knowledge and Priorities for Future Research in Late Effects after Hematopoietic Stem Cell Transplantation (HCT) for Severe Combined Immunodeficiency Patients: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects afte , 2017, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[23]  T. Flotte,et al.  Class I-restricted T-cell responses to a polymorphic peptide in a gene therapy clinical trial for α-1-antitrypsin deficiency , 2017, Proceedings of the National Academy of Sciences.

[24]  S. Weger,et al.  High Prevalence of Infectious Adeno-associated Virus (AAV) in Human Peripheral Blood Mononuclear Cells Indicative of T Lymphocytes as Sites of AAV Persistence , 2016, Journal of Virology.

[25]  A. Srivastava,et al.  High-Efficiency Transduction of Primary Human Hematopoietic Stem/Progenitor Cells by AAV6 Vectors: Strategies for Overcoming Donor-Variation and Implications in Genome Editing , 2016, Scientific Reports.

[26]  A. Singer,et al.  Timing and duration of MHC I positive selection signals are adjusted in the thymus to prevent lineage errors , 2016, Nature Immunology.

[27]  Z. Jing,et al.  αβ T-cell receptor bias in disease and therapy (Review). , 2016, International journal of oncology.

[28]  R. Herzog,et al.  Clinical development of gene therapy: results and lessons from recent successes , 2016, Molecular therapy. Methods & clinical development.

[29]  L. Notarangelo,et al.  Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency , 2016, Science Translational Medicine.

[30]  J. Abramson,et al.  AIRE: From promiscuous molecular partnerships to promiscuous gene expression , 2016, European journal of immunology.

[31]  J. B. Oliveira,et al.  Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency. , 2015, The Journal of clinical investigation.

[32]  E. Meffre,et al.  Lentiviral-mediated gene therapy restores B cell tolerance in Wiskott-Aldrich syndrome patients. , 2015, The Journal of clinical investigation.

[33]  H. Büning,et al.  Engineering the AAV capsid to optimize vector-host-interactions. , 2015, Current opinion in pharmacology.

[34]  M. van der Burg,et al.  B-cell reconstitution after lentiviral vector–mediated gene therapy in patients with Wiskott-Aldrich syndrome , 2015, The Journal of allergy and clinical immunology.

[35]  Arnauld Sergé,et al.  For3D: Full organ reconstruction in 3D, an automatized tool for deciphering the complexity of lymphoid organs. , 2015, Journal of immunological methods.

[36]  A. Sergé,et al.  Thymic Crosstalk Coordinates Medulla Organization and T-Cell Tolerance Induction , 2015, Front. Immunol..

[37]  Mikhail Shugay,et al.  MiXCR: software for comprehensive adaptive immunity profiling , 2015, Nature Methods.

[38]  Frederic D Bushman,et al.  Outcomes following gene therapy in patients with severe Wiskott-Aldrich syndrome. , 2015, JAMA.

[39]  Haochu Huang,et al.  The development and function of thymic B cells , 2015, Cellular and Molecular Life Sciences.

[40]  M. Agbandje-McKenna,et al.  Gene transfer properties and structural modeling of human stem cell-derived AAV. , 2014, Molecular therapy : the journal of the American Society of Gene Therapy.

[41]  T. Conlon,et al.  B-cell depletion is protective against anti-AAV capsid immune response: a human subject case study , 2014, Molecular therapy. Methods & clinical development.

[42]  A. Bhandoola,et al.  Chemokine treatment rescues profound T-lineage progenitor homing defect after bone marrow transplant conditioning in mice. , 2014, Blood.

[43]  Yosvany López,et al.  Development and validation of a new high-throughput method to investigate the clonality of HTLV-1-infected cells based on provirus integration sites , 2014, Genome Medicine.

[44]  T. Radstake,et al.  The aryl hydrocarbon receptor antagonist StemRegenin 1 promotes human plasmacytoid and myeloid dendritic cell development from CD34+ hematopoietic progenitor cells. , 2014, Stem cells and development.

[45]  D. Shah,et al.  An Overview of the Intrathymic Intricacies of T Cell Development , 2014, The Journal of Immunology.

[46]  Emily R. Levy,et al.  Image-guided intrathymic injection of multipotent stem cells supports lifelong T-cell immunity and facilitates targeted immunotherapy. , 2014, Blood.

[47]  M. V. D. van den Brink,et al.  Human proT-cells generated in vitro facilitate hematopoietic stem cell-derived T-lymphopoiesis in vivo and restore thymic architecture. , 2013, Blood.

[48]  T. Flotte,et al.  Human Treg responses allow sustained recombinant adeno-associated virus-mediated transgene expression. , 2013, The Journal of clinical investigation.

[49]  Emily R. Levy,et al.  Sex steroid blockade enhances thymopoiesis by modulating Notch signaling , 2013, The Journal of experimental medicine.

[50]  L. Meng,et al.  Autoreactive thymic B cells are efficient antigen-presenting cells of cognate self-antigens for T cell negative selection , 2013, Proceedings of the National Academy of Sciences.

[51]  Luca Biasco,et al.  Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome , 2013, Science.

[52]  A. Thrasher,et al.  Gene therapy for PIDs: Progress, pitfalls and prospects , 2013, Gene.

[53]  A. Fischer,et al.  Gene therapy of primary T cell immunodeficiencies. , 2013, Gene.

[54]  Liujiang Song,et al.  Optimizing the transduction efficiency of capsid-modified AAV6 serotype vectors in primary human hematopoietic stem cells in vitro and in a xenograft mouse model in vivo. , 2013, Cytotherapy.

[55]  K. High,et al.  Immune responses to AAV vectors: overcoming barriers to successful gene therapy. , 2013, Blood.

[56]  N. Taylor,et al.  Concise Review: Hematopoietic Stem Cell Transplantation: Targeting the Thymus , 2013, Stem cells.

[57]  J. Caamaño,et al.  The thymic medulla is required for Foxp3+ regulatory but not conventional CD4+ thymocyte development , 2013, The Journal of experimental medicine.

[58]  N. Taylor,et al.  Intrathymic progenitor cell transplantation across histocompatibility barriers results in the persistence of early thymic progenitors and T-cell differentiation. , 2013, Blood.

[59]  A. Sergé,et al.  Antigen Recognition By Autoreactive Cd4+ Thymocytes Drives Homeostasis Of The Thymic Medulla , 2012, PloS one.

[60]  M. Cavazzana‐Calvo,et al.  Human T-Lymphoid Progenitors Generated in a Feeder-Cell-Free Delta-Like-4 Culture System Promote T-Cell Reconstitution in NOD/SCID/γc−/− Mice , 2012, Stem cells.

[61]  Christof von Kalle,et al.  Integration Frequency and Intermolecular Recombination of rAAV Vectors in Non-human Primate Skeletal Muscle and Liver. , 2012, Molecular therapy : the journal of the American Society of Gene Therapy.

[62]  R. Jenq,et al.  Interleukin-22 Drives Endogenous Thymic Regeneration in Mice , 2012, Science.

[63]  A. Fischer,et al.  Primary Immunodeficiency Diseases: An Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency , 2011, Front. Immun..

[64]  M. V. D. van den Brink,et al.  Greater than the sum of their parts: combination strategies for immune regeneration following allogeneic hematopoietic stem cell transplantation. , 2011, Best practice & research. Clinical haematology.

[65]  A. Bhandoola,et al.  Signal integration and crosstalk during thymocyte migration and emigration , 2011, Nature reviews. Immunology.

[66]  A. Davidoff,et al.  Successful attenuation of humoral immunity to viral capsid and transgenic protein following AAV-mediated gene transfer with a non-depleting CD4 antibody and cyclosporine , 2011, Gene Therapy.

[67]  F. Alt,et al.  Abnormalities of Thymic Stroma may Contribute to Immune Dysregulation in Murine Models of Leaky Severe Combined Immunodeficiency , 2011, Front. Immun..

[68]  E. Palmer,et al.  Signaling in thymic selection. , 2011, Current opinion in immunology.

[69]  F. Bushman,et al.  The host genomic environment of the provirus determines the abundance of HTLV-1–infected T-cell clones , 2011, Blood.

[70]  M. Hallek,et al.  Gene transfer into human cord blood-derived CD34(+) cells by adeno-associated viral vectors. , 2010, Experimental hematology.

[71]  T. Heng,et al.  Sex Steroid Ablation Enhances Immune Reconstitution Following Cytotoxic Antineoplastic Therapy in Young Mice , 2010, The Journal of Immunology.

[72]  A. Fischer,et al.  Gene therapy for primary immunodeficiencies. , 2010, Immunology and allergy clinics of North America.

[73]  L. Muul,et al.  Somatic mosaicism in the Wiskott-Aldrich syndrome: molecular and functional characterization of genotypic revertants. , 2010, Clinical immunology.

[74]  N. Taylor,et al.  Intrathymic transplantation of bone marrow-derived progenitors provides long-term thymopoiesis. , 2010, Blood.

[75]  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.

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

[77]  N. Taylor,et al.  Efficient intrathymic gene transfer following in situ administration of a rAAV serotype 8 vector in mice and nonhuman primates. , 2009, Molecular therapy : the journal of the American Society of Gene Therapy.

[78]  U. Pannicke,et al.  Clinical and immunologic consequences of a somatic reversion in a patient with X-linked severe combined immunodeficiency. , 2008, Blood.

[79]  A. Singer,et al.  Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice , 2008, Nature Reviews Immunology.

[80]  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.

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

[82]  Michael J. DiCola,et al.  Unprecedented diversity of genotypic revertants in lymphocytes of a patient with Wiskott-Aldrich syndrome. , 2008, Blood.

[83]  C. Nguyen,et al.  ZAP-70 Restoration in Mice by In Vivo Thymic Electroporation , 2008, PloS one.

[84]  L. Zhong,et al.  Recombinant self-complementary adeno-associated virus serotype vector-mediated hematopoietic stem cell transduction and lineage-restricted, long-term transgene expression in a murine serial bone marrow transplantation model. , 2008, Human gene therapy.

[85]  L. Zhong,et al.  Stable integration of recombinant adeno-associated virus vector genomes after transduction of murine hematopoietic stem cells. , 2008, Human gene therapy.

[86]  David Klatzmann,et al.  Comprehensive Assessment and Mathematical Modeling of T Cell Population Dynamics and Homeostasis1 , 2008, The Journal of Immunology.

[87]  B. Kyewski,et al.  Promiscuous gene expression and the developmental dynamics of medullary thymic epithelial cells , 2007, European journal of immunology.

[88]  K. Hogquist,et al.  Thymic emigration revisited , 2007, The Journal of experimental medicine.

[89]  C. Benoist,et al.  Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire , 2007, The Journal of experimental medicine.

[90]  D. Russell.  AAV vectors, insertional mutagenesis, and cancer. , 2007, Molecular therapy : the journal of the American Society of Gene Therapy.

[91]  A. Gudkov,et al.  Keratinocyte growth factor (KGF) enhances postnatal T-cell development via enhancements in proliferation and function of thymic epithelial cells. , 2007, Blood.

[92]  D. Min,et al.  Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging. , 2007, Blood.

[93]  N. Olsen,et al.  Protein array autoantibody profiles for insights into systemic lupus erythematosus and incomplete lupus syndromes , 2006, Clinical and experimental immunology.

[94]  D. Klatzmann,et al.  Induction of antigen-specific tolerance by intrathymic injection of lentiviral vectors. , 2006, Blood.

[95]  T. Wada,et al.  Somatic revertant mosaicism in a patient with leukocyte adhesion deficiency type 1. , 2006, Blood.

[96]  A. Schambach,et al.  Gene therapy: X-SCID transgene leukaemogenicity , 2006, Nature.

[97]  F. Rieux-Laucat,et al.  Inherited and somatic CD3zeta mutations in a patient with T-cell deficiency. , 2006, The New England journal of medicine.

[98]  A. Douar,et al.  Gene Therapy Progress and Prospects – Vectorology: design and production of expression cassettes in AAV vectors , 2006, Gene Therapy.

[99]  J. Cooper,et al.  CNS-directed AAV2-mediated gene therapy ameliorates functional deficits in a murine model of infantile neuronal ceroid lipofuscinosis. , 2006, Molecular therapy : the journal of the American Society of Gene Therapy.

[100]  N. Hackett,et al.  AAV2-mediated CLN2 gene transfer to rodent and non-human primate brain results in long-term TPP-I expression compatible with therapy for LINCL , 2005, Gene Therapy.

[101]  N. Taylor,et al.  Intrathymic administration of hematopoietic progenitor cells enhances T cell reconstitution in ZAP-70 severe combined immunodeficiency. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[102]  Y. Hayashi,et al.  Oligoclonal expansion of T lymphocytes with multiple second-site mutations leads to Omenn syndrome in a patient with RAG1-deficient severe combined immunodeficiency. , 2005, Blood.

[103]  T. Heng,et al.  Activation of Thymic Regeneration in Mice and Humans following Androgen Blockade , 2005, The Journal of Immunology.

[104]  N. Taylor,et al.  In vivo correction of ZAP-70 immunodeficiency by intrathymic gene transfer. , 2005, The Journal of clinical investigation.

[105]  J. Sprent,et al.  Regulation of mature T cell homeostasis. , 2005, Seminars in immunology.

[106]  H. Petrie,et al.  Regulation of Thymus Size by Competition for Stromal Niches among Early T Cell Progenitors1 , 2004, The Journal of Immunology.

[107]  T. Nakahata,et al.  From bloodjournal.hematologylibrary.org at PENN STATE UNIVERSITY on February 23, 2013. For personal use only. , 2004 .

[108]  H. Bujard,et al.  Optimal design of a single recombinant adeno-associated virus derived from serotypes 1 and 2 to achieve more tightly regulated transgene expression from nonhuman primate muscle. , 2004, Molecular therapy : the journal of the American Society of Gene Therapy.

[109]  N. Manley,et al.  A domain of Foxn1 required for crosstalk-dependent thymic epithelial cell differentiation , 2003, Nature Immunology.

[110]  M. Kay,et al.  Helper virus-free, optically controllable, and two-plasmid-based production of adeno-associated virus vectors of serotypes 1 to 6. , 2003, Molecular therapy : the journal of the American Society of Gene Therapy.

[111]  F. Candotti,et al.  Second-site mutation in the Wiskott-Aldrich syndrome (WAS) protein gene causes somatic mosaicism in two WAS siblings. , 2003, The Journal of clinical investigation.

[112]  B. Aronow,et al.  Restricting Zap70 Expression to CD4+CD8+ Thymocytes Reveals a T Cell Receptor–dependent Proofreading Mechanism Controlling the Completion of Positive Selection , 2003, The Journal of experimental medicine.

[113]  Mark S. Anderson,et al.  Projection of an Immunological Self Shadow Within the Thymus by the Aire Protein , 2002, Science.

[114]  K. Yamaguchi,et al.  T-cell lines from 2 patients with adenosine deaminase (ADA) deficiency showed the restoration of ADA activity resulted from the reversion of an inherited mutation. , 2001, Blood.

[115]  I. Goldschneider,et al.  The Importation of Hematogenous Precursors by the Thymus Is a Gated Phenomenon in Normal Adult Mice , 2001, The Journal of experimental medicine.

[116]  J. Wilson,et al.  Route of administration determines induction of T-cell-independent humoral responses to adeno-associated virus vectors. , 2000, Molecular therapy : the journal of the American Society of Gene Therapy.

[117]  V. Wahn,et al.  Diversity, functionality, and stability of the T cell repertoire derived in vivo from a single human T cell precursor. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[118]  S. Berzins,et al.  The Role of the Thymus and Recent Thymic Migrants in the Maintenance of the Adult Peripheral Lymphocyte Pool , 1998, The Journal of experimental medicine.

[119]  A. Salvetti,et al.  Factors influencing recombinant adeno-associated virus production. , 1998, Human gene therapy.

[120]  R. DeMatteo,et al.  Long-lasting adenovirus transgene expression in mice through neonatal intrathymic tolerance induction without the use of immunosuppression , 1997, Journal of virology.

[121]  A. Nienhuis,et al.  High-level globin gene expression mediated by a recombinant adeno-associated virus genome that contains the 3' gamma globin gene regulatory element and integrates as tandem copies in erythroid cells. , 1997, Blood.

[122]  P. Malik,et al.  Recombinant adeno-associated virus mediates a high level of gene transfer but less efficient integration in the K562 human hematopoietic cell line , 1997, Journal of virology.

[123]  Juan Li,et al.  Gene Transfer by Adeno-Associated Virus Vectors into the Central Nervous System , 1997, Experimental Neurology.

[124]  R. Strumpf,et al.  Long-term gene transfer in porcine myocardium after coronary infusion of an adeno-associated virus vector. , 1996, The Annals of thoracic surgery.

[125]  U. Dirksen,et al.  Atypical X-linked severe combined immunodeficiency due to possible spontaneous reversion of the genetic defect in T cells. , 1996, The New England journal of medicine.

[126]  J. Puck,et al.  Spontaneous in vivo reversion to normal of an inherited mutation in a patient with adenosine deaminase deficiency , 1996, Nature Genetics.

[127]  G. Breese,et al.  Differential and persistent expression patterns of CNS gene transfer by an adeno-associated virus (AAV) vector , 1996, Brain Research.

[128]  J. Sprent,et al.  Thymus-grafted SCID mice show transient thymopoiesis and limited depletion of V beta 11+ T cells , 1992, The Journal of experimental medicine.

[129]  G. Spangrude,et al.  Differentiation of hematopoietic stem cells in irradiated mouse thymic lobes. Kinetics and phenotype of progeny. , 1990, Journal of immunology.

[130]  M. Claesson,et al.  Thymic Epithelial Cells , 1990, Scandinavian journal of immunology.

[131]  Mark M. Davis,et al.  T-cell antigen receptor genes and T-cell recognition , 1988, Nature.

[132]  R. Scollay,et al.  Dynamics of Early T Cells: Prothymocyte Migration and Proliferation in the Adult Mouse Thymus , 1986, Immunological reviews.

[133]  D. Greiner,et al.  Studies of thymocytopoiesis in rats and mice. I. Kinetics of appearance of thymocytes using a direct intrathymic adoptive transfer assay for thymocyte precursors , 1986, The Journal of experimental medicine.

[134]  A. Bhandoola,et al.  Intrathymic Injection. , 2016, Methods in molecular biology.

[135]  H. Waldmann,et al.  Enhanced efficacy from gene therapy in Pompe disease using coreceptor blockade. , 2015, Human gene therapy.

[136]  I. Anegon,et al.  Measuring immune responses to recombinant AAV gene transfer. , 2011, Methods in molecular biology.

[137]  L. Sellner,et al.  Pseudotyped recombinant adeno-associated viral vectors mediate efficient gene transfer into primary human CD34(+) peripheral blood progenitor cells. , 2010, Cytotherapy.

[138]  S. Holland,et al.  Reversion mutations in patients with leukocyte adhesion deficiency type-1 (LAD-1). , 2008, Blood.

[139]  E. Spanopoulou,et al.  Thymic microenvironments, 3-D versus 2-D? , 1999, Seminars in immunology.

[140]  Donald W. Pfaff,et al.  Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain , 1994, Nature Genetics.

[141]  Susan M. Schlenner,et al.  Thymus-autonomous T cell development in the absence of progenitor import , 2012, The Journal of experimental medicine.

[142]  J. D. Di Santo,et al.  Brief Definitive Report , 2022 .