Federico Mingozzi

Summary

Affiliation: The Children's Hospital of Philadelphia
Country: USA

Publications

  1. ncbi request reprint Immune responses to AAV in clinical trials
    Federico Mingozzi
    Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Curr Gene Ther 7:316-24. 2007
  2. pmc Prevalence and pharmacological modulation of humoral immunity to AAV vectors in gene transfer to synovial tissue
    F Mingozzi
    Center of Cellular and Molecular Therapeutics, The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Gene Ther 20:417-24. 2013
  3. pmc Pharmacological modulation of humoral immunity in a nonhuman primate model of AAV gene transfer for hemophilia B
    Federico Mingozzi
    Division of Hematology, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Mol Ther 20:1410-6. 2012
  4. ncbi request reprint Immune responses to AAV in clinical trials
    Federico Mingozzi
    Children s Hospital of Philadelphia, PA 19104, USA
    Curr Gene Ther 11:321-30. 2011
  5. pmc Modulation of tolerance to the transgene product in a nonhuman primate model of AAV-mediated gene transfer to liver
    Federico Mingozzi
    Division of Hematology and Center for Cellular and Molecular Therapeutics, The Children s Hospital of Philadelphia, PA 19104, USA
    Blood 110:2334-41. 2007
  6. pmc Peripheral transvenular delivery of adeno-associated viral vectors to skeletal muscle as a novel therapy for hemophilia B
    Valder R Arruda
    University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    Blood 115:4678-88. 2010
  7. pmc Modulation of CD8+ T cell responses to AAV vectors with IgG-derived MHC class II epitopes
    Daniel J Hui
    Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    Mol Ther 21:1727-37. 2013
  8. pmc AAV-1-mediated gene transfer to skeletal muscle in humans results in dose-dependent activation of capsid-specific T cells
    Federico Mingozzi
    Division of Hematology and Center for Cellular and Molecular Therapeutics, The Children s Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA
    Blood 114:2077-86. 2009
  9. pmc Prevention of cytotoxic T lymphocyte responses to factor IX-expressing hepatocytes by gene transfer-induced regulatory T cells
    Eric Dobrzynski
    Department of Pediatrics, The Children s Hospital of Philadelphia and University of Pennsylvania Medical School, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 103:4592-7. 2006
  10. pmc Proteasome inhibitors decrease AAV2 capsid derived peptide epitope presentation on MHC class I following transduction
    Jonathan D Finn
    Department of Pediatrics, Division of Hematology, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Mol Ther 18:135-42. 2010

Collaborators

Detail Information

Publications32

  1. ncbi request reprint Immune responses to AAV in clinical trials
    Federico Mingozzi
    Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Curr Gene Ther 7:316-24. 2007
    ....
  2. pmc Prevalence and pharmacological modulation of humoral immunity to AAV vectors in gene transfer to synovial tissue
    F Mingozzi
    Center of Cellular and Molecular Therapeutics, The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Gene Ther 20:417-24. 2013
    ..This work provides insights into strategies to overcome the limitation of pre-existing humoral immunity to AAV vectors...
  3. pmc Pharmacological modulation of humoral immunity in a nonhuman primate model of AAV gene transfer for hemophilia B
    Federico Mingozzi
    Division of Hematology, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Mol Ther 20:1410-6. 2012
    ..IX transgene product in plasma. Though the number of animals is small, this study supports for the safety and efficacy of B cell-targeting therapies to eradicate NAb developed following AAV-mediated gene transfer...
  4. ncbi request reprint Immune responses to AAV in clinical trials
    Federico Mingozzi
    Children s Hospital of Philadelphia, PA 19104, USA
    Curr Gene Ther 11:321-30. 2011
    ....
  5. pmc Modulation of tolerance to the transgene product in a nonhuman primate model of AAV-mediated gene transfer to liver
    Federico Mingozzi
    Division of Hematology and Center for Cellular and Molecular Therapeutics, The Children s Hospital of Philadelphia, PA 19104, USA
    Blood 110:2334-41. 2007
    ....
  6. pmc Peripheral transvenular delivery of adeno-associated viral vectors to skeletal muscle as a novel therapy for hemophilia B
    Valder R Arruda
    University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    Blood 115:4678-88. 2010
    ..Collectively, these results demonstrate the feasibility of this approach for treatment of HB and highlight the importance of IS to prevent immune responses to the FIX transgene product...
  7. pmc Modulation of CD8+ T cell responses to AAV vectors with IgG-derived MHC class II epitopes
    Daniel J Hui
    Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    Mol Ther 21:1727-37. 2013
    ..This proof-of-concept study demonstrates modulation of CD8+ T cell reactivity to an antigen using regulatory T cell epitopes is possible...
  8. pmc AAV-1-mediated gene transfer to skeletal muscle in humans results in dose-dependent activation of capsid-specific T cells
    Federico Mingozzi
    Division of Hematology and Center for Cellular and Molecular Therapeutics, The Children s Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA
    Blood 114:2077-86. 2009
    ..Whether they also limit the duration of expression of the transgene at higher doses is unclear, and will require additional analyses at later time points...
  9. pmc Prevention of cytotoxic T lymphocyte responses to factor IX-expressing hepatocytes by gene transfer-induced regulatory T cells
    Eric Dobrzynski
    Department of Pediatrics, The Children s Hospital of Philadelphia and University of Pennsylvania Medical School, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 103:4592-7. 2006
    ..This result suggests that augmentation of regulatory T cell activation should provide new means to avoid destructive immune responses in gene transfer...
  10. pmc Proteasome inhibitors decrease AAV2 capsid derived peptide epitope presentation on MHC class I following transduction
    Jonathan D Finn
    Department of Pediatrics, Division of Hematology, The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Mol Ther 18:135-42. 2010
    ....
  11. ncbi request reprint Safety and efficacy of factor IX gene transfer to skeletal muscle in murine and canine hemophilia B models by adeno-associated viral vector serotype 1
    Valder R Arruda
    Department of Pediatrics, University of Pennsylvani Medical Center, The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Blood 103:85-92. 2004
    ..ix...
  12. ncbi request reprint Therapeutic levels of factor IX expression using a muscle-specific promoter and adeno-associated virus serotype 1 vector
    Yi Lin Liu
    Department of Pediatrics, Children s Hospital of Philadelphia and University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA
    Hum Gene Ther 15:783-92. 2004
    ..IX transgene product in mice with F.IX gene deletion, indicating that the risk of humoral immune responses remains in the context of an immunologically unfavorable mutation...
  13. pmc Safety of AAV factor IX peripheral transvenular gene delivery to muscle in hemophilia B dogs
    Virginia Haurigot
    Division of Hematology and Center for Cellular and Molecular Therapeutics, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Mol Ther 18:1318-29. 2010
    ..In summary, this study in a large animal model of HB demonstrates that therapeutic levels of gene transfer can be safely achieved using a novel route of intravascular gene transfer to muscle...
  14. doi request reprint Safety and efficacy of subretinal readministration of a viral vector in large animals to treat congenital blindness
    Defne Amado
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Sci Transl Med 2:21ra16. 2010
    ..Thus, subretinal readministration of rAAV2 in animals is safe and effective, even in the setting of preexisting immunity to the vector, a parameter that has been used to exclude patients from gene therapy trials...
  15. pmc Capsid antigen presentation flags human hepatocytes for destruction after transduction by adeno-associated viral vectors
    Gary C Pien
    Division of Allergy and Immunology, Children s Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Clin Invest 119:1688-95. 2009
    ....
  16. pmc Diverse IgG subclass responses to adeno-associated virus infection and vector administration
    Samuel L Murphy
    Center for Cell and Molecular Therapeutics, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104 4318, USA
    J Med Virol 81:65-74. 2009
    ..Analysis of IgG subclass distribution of anti-AAV capsid antibodies indicates a complex, non-uniform pattern of responses to this viral antigen. J. Med. Virol. 81:65-74, 2009. (c) 2008 Wiley-Liss, Inc...
  17. ncbi request reprint CD8(+) T-cell responses to adeno-associated virus capsid in humans
    Federico Mingozzi
    The Children s Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA
    Nat Med 13:419-22. 2007
    ..In addition, we show that AAV-2 induced human T cells proliferate upon exposure to alternate AAV serotypes, indicating that other serotypes are unlikely to evade capsid-specific immune responses...
  18. pmc Induction of immune tolerance to coagulation factor IX antigen by in vivo hepatic gene transfer
    Federico Mingozzi
    Department of Pediatrics, The Children s Hospital of Philadelphia, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA
    J Clin Invest 111:1347-56. 2003
    ..With a strain-dependent rate of success, tolerance to murine F.IX was induced in mice with a large F.IX gene deletion, supporting the relevance of these data for treatment of hemophilia B and other genetic diseases...
  19. doi request reprint Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial
    Albert M Maguire
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Lancet 374:1597-605. 2009
    ..We therefore did a phase 1 trial to assess the effect of gene therapy on retinal and visual function in children and adults with Leber's congenital amaurosis...
  20. pmc Improved hepatic gene transfer by using an adeno-associated virus serotype 5 vector
    Federico Mingozzi
    Department of Pediatrics, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA
    J Virol 76:10497-502. 2002
    ..The subpopulations of hepatocytes transduced with either vector widely overlap, with the AAV-5 vector transducing additional hepatocytes and showing a wider area of transgene expression throughout the liver parenchyma...
  21. pmc Host and vector-dependent effects on the risk of germline transmission of AAV vectors
    Patricia Favaro
    The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Mol Ther 17:1022-30. 2009
    ....
  22. pmc Undetectable transcription of cap in a clinical AAV vector: implications for preformed capsid in immune responses
    Bernd Hauck
    Center for Cellular and Molecular Therapeutics, Department of Pediatrics, The Childrens Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Mol Ther 17:144-52. 2009
    ..Preformed capsid protein is implicated as the source of epitopes recognized by CD8(+) T cells that eliminated vector-transduced cells in the clinical study...
  23. ncbi request reprint Induction of antigen-specific CD4+ T-cell anergy and deletion by in vivo viral gene transfer
    Eric Dobrzynski
    The Children s Hospital of Philadelphia, Abramson Research Center 302, 34th St and Civic Center Blvd, Philadelphia, PA 19104, USA
    Blood 104:969-77. 2004
    ..These data provide direct evidence that transgene expression following in vivo viral gene transfer can induce CD4+ T-cell tolerance to the transgene product, involving anergy and deletion mechanisms...
  24. pmc Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer
    George Buchlis
    Division of Hematology and Center for Cellular and Molecular Therapeutics, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Blood 119:3038-41. 2012
    ..This is the longest reported transgene expression to date from a parenterally administered AAV vector, with broad implications for the future of muscle-directed gene transfer...
  25. ncbi request reprint Overcoming preexisting humoral immunity to AAV using capsid decoys
    Federico Mingozzi
    Department of Pediatrics and Center for Cellular and Molecular Therapeutics, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Sci Transl Med 5:194ra92. 2013
    ..Our work suggests that optimizing the ratio of full/empty capsids in the final formulation of vector, based on a patient's anti-AAV titers, will maximize the efficacy of gene transfer after systemic vector delivery. ..
  26. ncbi request reprint Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response
    Catherine S Manno
    The Children s Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania, 19104, USA
    Nat Med 12:342-7. 2006
    ..We conclude that rAAV-2 vectors can transduce human hepatocytes in vivo to result in therapeutically relevant levels of F.IX, but that future studies in humans may require immunomodulation to achieve long-term expression...
  27. doi request reprint Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges
    Federico Mingozzi
    Center for Cellular and Molecular Therapeutics, The Children s Hospital of Philadelphia, 3501 Civic Center Boulevard, 5th Floor CTRB, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Genet 12:341-55. 2011
    ..Recent exciting results have raised hopes for the treatment of many other diseases. As we discuss here, the prospects and challenges for AAV gene therapy are to a large extent dependent on the target tissue and the specific disease...
  28. pmc Assessing the potential for AAV vector genotoxicity in a murine model
    Hojun Li
    Department of Hematology, Children s Hospital of Philadelphia, Philadelphia, PA, USA
    Blood 117:3311-9. 2011
    ..No integration events were identified as causing increased oncogene expression. Thus, we did not find evidence that AAV vectors cause insertional activation of oncogenes and subsequent tumor formation...
  29. doi request reprint AAV2 gene therapy readministration in three adults with congenital blindness
    Jean Bennett
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 309 Stellar Chance Labs, 422 Curie Boulevard, Philadelphia, PA 19104, USA
    Sci Transl Med 4:120ra15. 2012
    ....
  30. ncbi request reprint Identification of mouse AAV capsid-specific CD8+ T cell epitopes
    Denise E Sabatino
    The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Mol Ther 12:1023-33. 2005
    ..Identification of these epitopes will facilitate studies of immune response to AAV capsid in mouse models...
  31. pmc Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer
    Jeannette Bennicelli
    Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6069, USA
    Mol Ther 16:458-65. 2008
    ..The data demonstrate that AAV2.RPE65 delivers the RPE65 transgene efficiently and quickly to the appropriate target cells in vivo in animal models. This vector holds great promise for treatment of LCA due to RPE65 mutations...
  32. pmc Immune responses to AAV vectors: overcoming barriers to successful gene therapy
    Federico Mingozzi
    Division of Hematology, The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Blood 122:23-36. 2013
    ....