T R Flotte

Summary

Affiliation: University of Florida
Country: USA

Publications

  1. ncbi Adeno-associated virus: a ubiquitous commensal of mammals
    Terence R Flotte
    Department of Pediatrics, and Genetics Institute, University of Florida, Gainesville, FL 32610, USA
    Hum Gene Ther 16:401-7. 2005
  2. ncbi Adeno-associated virus-based gene therapy for inherited disorders
    Terence R Flotte
    Department of Pediatrics, University of Florida, Gainesville 32610, USA
    Pediatr Res 58:1143-7. 2005
  3. ncbi Phase I trial of intranasal and endobronchial administration of a recombinant adeno-associated virus serotype 2 (rAAV2)-CFTR vector in adult cystic fibrosis patients: a two-part clinical study
    Terence R Flotte
    Department of Pediatrics and Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610 0296, USA
    Hum Gene Ther 14:1079-88. 2003
  4. ncbi Recent developments in recombinant AAV-mediated gene therapy for lung diseases
    Terence R Flotte
    Powell Gene Therapy Center, Genetics Institute, Department of Pediatrics, University of Florida, 1600 SW Archer Rd, Box 100296, Gainesville, FL 32610 0296, USA
    Curr Gene Ther 5:361-6. 2005
  5. ncbi Size does matter: overcoming the adeno-associated virus packaging limit
    T R Flotte
    Powell Gene Therapy Center, University of Florida, Gainesville, Florida 32610 0266, USA
    Respir Res 1:16-8. 2000
  6. ncbi Gene therapy in cystic fibrosis
    T R Flotte
    Powell Gene Therapy Center, University of Florida Genetics Institute, Gainesville, FL, USA
    Chest 120:124S-131S. 2001
  7. ncbi The pros and cons of immunomodulatory IL-10 gene therapy with recombinant AAV in a Cftr-/- -dependent allergy mouse model
    C Mueller
    Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Gene Ther 16:172-83. 2009
  8. ncbi Adeno-associated virus vector-mediated IL-10 gene delivery prevents type 1 diabetes in NOD mice
    K Goudy
    Department of Pathology, University of Florida, Gainesville, FL 32610, USA
    Proc Natl Acad Sci U S A 98:13913-8. 2001
  9. ncbi Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy
    Mark L Brantly
    Department of Medicine, University of Florida, Gainesville, FL 32611, USA
    Proc Natl Acad Sci U S A 106:16363-8. 2009
  10. ncbi Stable therapeutic serum levels of human alpha-1 antitrypsin (AAT) after portal vein injection of recombinant adeno-associated virus (rAAV) vectors
    S Song
    Department of Pediatrics, University of Florida Genetics Institute, Gainesville, FL 32610-0266, USA
    Gene Ther 8:1299-306. 2001

Detail Information

Publications86

  1. ncbi Adeno-associated virus: a ubiquitous commensal of mammals
    Terence R Flotte
    Department of Pediatrics, and Genetics Institute, University of Florida, Gainesville, FL 32610, USA
    Hum Gene Ther 16:401-7. 2005
  2. ncbi Adeno-associated virus-based gene therapy for inherited disorders
    Terence R Flotte
    Department of Pediatrics, University of Florida, Gainesville 32610, USA
    Pediatr Res 58:1143-7. 2005
    ..The evaluation of safety and efficacy of these newer agents is ongoing...
  3. ncbi Phase I trial of intranasal and endobronchial administration of a recombinant adeno-associated virus serotype 2 (rAAV2)-CFTR vector in adult cystic fibrosis patients: a two-part clinical study
    Terence R Flotte
    Department of Pediatrics and Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610 0296, USA
    Hum Gene Ther 14:1079-88. 2003
    ..These data indicate the need for continued evaluation of rAAV-CFTR vectors in additional clinical trials...
  4. ncbi Recent developments in recombinant AAV-mediated gene therapy for lung diseases
    Terence R Flotte
    Powell Gene Therapy Center, Genetics Institute, Department of Pediatrics, University of Florida, 1600 SW Archer Rd, Box 100296, Gainesville, FL 32610 0296, USA
    Curr Gene Ther 5:361-6. 2005
    ..In addition, the availability of an abundance of novel rAAV serotypes, each with its own receptor tropism, has expanded the range of possibilities for long-term success of gene therapy in the respiratory tract...
  5. ncbi Size does matter: overcoming the adeno-associated virus packaging limit
    T R Flotte
    Powell Gene Therapy Center, University of Florida, Gainesville, Florida 32610 0266, USA
    Respir Res 1:16-8. 2000
    ..This technology could improve the chances for successful gene therapy of diseases like cystic fibrosis or Duchenne muscular dystrophy that lead to significant pulmonary morbidity...
  6. ncbi Gene therapy in cystic fibrosis
    T R Flotte
    Powell Gene Therapy Center, University of Florida Genetics Institute, Gainesville, FL, USA
    Chest 120:124S-131S. 2001
    ..These findings could lead to more efficient and targeted lung delivery of aerosolized gene vectors in the future...
  7. ncbi The pros and cons of immunomodulatory IL-10 gene therapy with recombinant AAV in a Cftr-/- -dependent allergy mouse model
    C Mueller
    Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Gene Ther 16:172-83. 2009
    ..These results highlight that while IL-10 gene therapy is very effective for treating allergic responses caution must be taken with the prolonged secretion of IL-10...
  8. ncbi Adeno-associated virus vector-mediated IL-10 gene delivery prevents type 1 diabetes in NOD mice
    K Goudy
    Department of Pathology, University of Florida, Gainesville, FL 32610, USA
    Proc Natl Acad Sci U S A 98:13913-8. 2001
    ....
  9. ncbi Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy
    Mark L Brantly
    Department of Medicine, University of Florida, Gainesville, FL 32611, USA
    Proc Natl Acad Sci U S A 106:16363-8. 2009
    ..These findings suggest that immune responses to AAV capsid that develop after i.m. injection of a serotype 1 rAAV vector expressing AAT do not completely eliminate transduced cells in this context...
  10. ncbi Stable therapeutic serum levels of human alpha-1 antitrypsin (AAT) after portal vein injection of recombinant adeno-associated virus (rAAV) vectors
    S Song
    Department of Pediatrics, University of Florida Genetics Institute, Gainesville, FL 32610-0266, USA
    Gene Ther 8:1299-306. 2001
    ..There was no evidence of hepatic toxicity. These data indicate that liver-directed rAAV-based gene therapy is effective in the murine model, and hence might be feasible for treatment of human AAT deficiency...
  11. ncbi Recombinant adeno-associated virus-mediated alpha-1 antitrypsin gene therapy prevents type I diabetes in NOD mice
    S Song
    Department of Pharmaceutics, University of Florida, Gainesville, FL 32610, USA
    Gene Ther 11:181-6. 2004
    ..This study suggests a potential therapeutic role for AAT in preventing type I diabetes as well as the ability of AAV gene therapy-based approaches to ameliorate disease effectively...
  12. ncbi Effect of DNA-dependent protein kinase on the molecular fate of the rAAV2 genome in skeletal muscle
    S Song
    Genetics Institute, Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610, USA
    Proc Natl Acad Sci U S A 98:4084-8. 2001
    ..These results indicate that DNA-PK is involved in the formation of circular rAAV episomes...
  13. ncbi Recombinant adeno-associated virus vectors for gene therapy
    Thomas J Conlon
    University of Florida College of Medicine, Department of Pediatrics, Box 100296, Gainesville, FL 32610-0296, USA
    Expert Opin Biol Ther 4:1093-101. 2004
    ..Each of these areas is individually discussed, as are recent applications in vivo in preclinical models and clinical trials...
  14. ncbi Production of clinical-grade recombinant adeno-associated virus vectors
    Richard O Snyder
    Powell Gene Therapy Center, University of Florida Genetics Institute, Department of Pediatrics, 1600 SW Archer Road, Gainesville, FL 32610-0266, USA
    Curr Opin Biotechnol 13:418-23. 2002
    ..The clinical manufacture of rAAV vectors has supported phase I and phase II trials, showing that adeno-associated virus serotype 2 vectors are safe when administered to humans...
  15. ncbi Recombinant adeno-associated virus gene therapy for cystic fibrosis and alpha(1)-antitrypsin deficiency
    Terence R Flotte
    Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610-0266, USA
    Chest 121:98S-102S. 2002
  16. ncbi In vitro and in vivo functional characterization of gutless recombinant SV40-derived CFTR vectors
    C Mueller
    Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Gene Ther 17:227-37. 2010
    ..The reduction in inflammatory cytokine levels led to an evident decrease in neutrophil influx to the airways. These results indicate that further study of the application of rSV40-CFTR to CF gene therapy is warranted...
  17. ncbi Efficient hepatic delivery and expression from a recombinant adeno-associated virus 8 pseudotyped alpha1-antitrypsin vector
    Thomas J Conlon
    Department of Pediatrics and Powell Gene Therapy Center, University of Florida, Gainesville, FL 32608, USA
    Mol Ther 12:867-75. 2005
    ..Therefore, pseudotyped AAV8 provides a vehicle to infect a high percentage of hepatocytes stably and thereby express therapeutic molecules to modify AAT PiZ transcripts...
  18. ncbi Intramuscular administration of recombinant adeno-associated virus 2 alpha-1 antitrypsin (rAAV-SERPINA1) vectors in a nonhuman primate model: safety and immunologic aspects
    Sihong Song
    Powell Gene Therapy Center of the University of Florida Genetics Institute, University of Florida, Gainesville, Florida 32615, USA
    Mol Ther 6:329-35. 2002
    ..These studies indicate that the risks of immune reaction and germline transmission after intramuscular injection of rAAV-SERPINA1 in nonhuman primates are relatively low within the range of vector doses studied...
  19. ncbi Apparently nonspecific enzyme elevations after portal vein delivery of recombinant adeno-associated virus serotype 2 vector in hepatitis C virus-infected chimpanzees
    Terence R Flotte
    Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Hum Gene Ther 19:681-9. 2008
    ..These data indicate an increased susceptibility to subclinical liver toxicity from portal vein injection of rAAV2 in the presence of HCV infection...
  20. ncbi Systemic correction of a fatty acid oxidation defect by intramuscular injection of a recombinant adeno-associated virus vector
    Thomas J Conlon
    Department of Pediatrics, Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610, and Department of Pediatrics, Children s Hospital of Pittsburgh, PA, USA
    Hum Gene Ther 17:71-80. 2006
    ..This study is the first to demonstrate the systemic correction of a fatty acid oxidation disorder with rAAV and the utility of MRS as a noninvasive method to monitor SCAD correction after in vivo gene therapy...
  21. ncbi Gene delivery in renal tubular epithelial cells using recombinant adeno-associated viral vectors
    Sifeng Chen
    Department of Medicine, University of Florida, Gainesville, Florida 32610, USA
    J Am Soc Nephrol 14:947-58. 2003
    ....
  22. ncbi Localized gene expression following administration of adeno-associated viral vectors via pancreatic ducts
    Scott A Loiler
    Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610, USA
    Mol Ther 12:519-27. 2005
    ..This study demonstrates that rAAV vectors can be designed to deliver therapeutic genes efficiently to the pancreas and achieve high levels of gene expression and may be useful in treating pancreatic disorders, including T1D...
  23. ncbi Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults
    Mark L Brantly
    Department of Medicine, University of Florida, Gainesville, FL 32611, USA
    Hum Gene Ther 17:1177-86. 2006
    ....
  24. ncbi Recombinant AAV serotype and capsid mutant comparison for pulmonary gene transfer of alpha-1-antitrypsin using invasive and noninvasive delivery
    Rejean Liqun Wang
    Department of Pediatrics and Powell Gene Therapy Center, University of Florida, Gainesville, Florida, USA
    Mol Ther 17:81-7. 2009
    ..Overall, rAAV8 was the most promising vector for the future application in gene therapy of pulmonary diseases such as AAT deficiency-related emphysema...
  25. ncbi Gene therapy for cystic fibrosis
    T R Flotte
    University of Florida Genetics Institute, JHMHSC, Gainesville 32610 0266, USA
    Curr Opin Mol Ther 1:510-6. 1999
    ..In this review, the relevant aspects of airway biology, the pathophysiological CF lung disease, and the characteristics of the currently available vector systems are discussed...
  26. ncbi Systemic overexpression of IL-10 induces CD4+CD25+ cell populations in vivo and ameliorates type 1 diabetes in nonobese diabetic mice in a dose-dependent fashion
    Kevin S Goudy
    Department of Pathology, Powell Gene Therapy Center, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA
    J Immunol 171:2270-8. 2003
    ..This study indicates the potential for immunomodulatory gene therapy to prevent autoimmune diseases, including type 1 diabetes, and implicates IL-10 as a molecule capable of increasing the percentages of regulatory cells in vivo...
  27. ncbi Neonatal intraperitoneal or intravenous injections of recombinant adeno-associated virus type 8 transduce dorsal root ganglia and lower motor neurons
    Kevin D Foust
    Department of Pediatrics, Evelyn F and William L McKnight Brian Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA
    Hum Gene Ther 19:61-70. 2008
    ..Our data suggest that systemic injection of rAAV8 is not an effective delivery route to target lower motor neurons, but could be useful for targeting sensory pathways in chronic pain...
  28. ncbi Therapeutic level of functional human alpha 1 antitrypsin (hAAT) secreted from murine muscle transduced by adeno-associated virus (rAAV1) vector
    Yuanqing Lu
    Department of Pharmaceutics, University of Florida College of Pharmacy, Gainesville, FL 32610, USA
    J Gene Med 8:730-5. 2006
    ..These results provide strong support for the functionality of AAT in ongoing clinical studies of muscle-directed AAT gene therapy...
  29. ncbi Clinical gene therapy using recombinant adeno-associated virus vectors
    C Mueller
    Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Gene Ther 15:858-63. 2008
    ..The explosion of capsid isolates available for use as vectors to over 120 has now provided the potential to broaden the application of AAV-based gene therapy to other cell types...
  30. ncbi Recombinant adeno-associated virus vectors for cystic fibrosis gene therapy
    T R Flotte
    Powell Gene Therapy Center, University of Florida, Gainesville 32610 0266, USA
    Curr Opin Mol Ther 3:497-502. 2001
    ....
  31. ncbi In vivo expression of human ATP:cob(I)alamin adenosyltransferase (ATR) using recombinant adeno-associated virus (rAAV) serotypes 2 and 8
    Kirsten E Erger
    Department of Pediatrics, Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610, USA
    J Gene Med 9:462-9. 2007
    ..ATR functions within the mitochondria matrix in the final conversion of cobalamin into coenzyme B(12), adenosylcobalamin (AdoCbl). AdoCbl is a required coenzyme for the mitochondrial enzyme methylmalonyl-CoA mutase (MCM)...
  32. ncbi Gene therapy for cystic fibrosis
    Christian Mueller
    Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, USA
    Clin Rev Allergy Immunol 35:164-78. 2008
    ..This learning curve has led to the optimization of vector technology and an appreciation of immune and mechanical barriers that have to be overcome for successful delivery...
  33. ncbi Functional characterization of a recombinant adeno-associated virus 5-pseudotyped cystic fibrosis transmembrane conductance regulator vector
    Jeffrey Sirninger
    Powell Gene Therapy Center, UF Genetics Institute, Department of Pediatrics and Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32619-0296, USA
    Hum Gene Ther 15:832-41. 2004
    ..These studies provide functional characterization of a new version of rAAV-CFTR vectors...
  34. ncbi Partial correction of the CFTR-dependent ABPA mouse model with recombinant adeno-associated virus gene transfer of truncated CFTR gene
    Christian Mueller
    Department of Pediatrics and Powell Gene Therapy Center, College of Medicine, University of Florida, Gainesville, FL, USA
    J Gene Med 10:51-60. 2008
    ..Gene therapy with rAAV5Delta-264CFTR attenuated the hyper-IgE response in this reproducible CF mouse model of ABPA, with systemic effects also evident in the cytokine response of stimulated splenocytes...
  35. ncbi Phase I trial of intramuscular injection of a recombinant adeno-associated virus alpha 1-antitrypsin (rAAV2-CB-hAAT) gene vector to AAT-deficient adults
    Terence R Flotte
    Department of Pediatrics, University of Florida, Gainesville, USA
    Hum Gene Ther 15:93-128. 2004
    ....
  36. ncbi Gene therapy progress and prospects: recombinant adeno-associated virus (rAAV) vectors
    T R Flotte
    Department of Pediatrics and the Powell Gene Therapy Center, University of Florida, Gainesville, FL, USA
    Gene Ther 11:805-10. 2004
  37. ncbi Teaching hypothesis-oriented thinking to medical students: the University of Florida's clinical investigation program
    P W Stacpoole
    General Clinical Research Center GCRC, J Hillis Miller Health Center, Gainesville, FL 32610, USA
    Acad Med 76:287-92. 2001
    ....
  38. ncbi Dual reporter comparative indexing of rAAV pseudotyped vectors in chimpanzee airway
    Terence R Flotte
    Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    Mol Ther 18:594-600. 2010
    ..T-cell responses to AAV5 capsid were stronger than AAV1 capsid. This dual vector indexing approach may be useful in selecting lead vector serotypes for clinical gene therapy and suggests rAAV1 is preferred for cystic fibrosis...
  39. ncbi The signal and the trap: targeted delivery and retention of proteins in the mitochondrion
    Terence R Flotte
    Department of Pediatrics, Powell Gene Therapy Center, University of Florida, Gainesville 32611, USA
    Mol Ther 7:715-6. 2003
  40. ncbi The pyruvate dehydrogenase complex as a target for gene therapy
    Peter W Stacpoole
    Department of Medicine, Division of Endocrinology and Metabolism, University of Florida, College of Medicine, Gainesville, FL 32610, USA
    Curr Gene Ther 3:239-45. 2003
    ....
  41. ncbi In vivo post-transcriptional gene silencing of alpha-1 antitrypsin by adeno-associated virus vectors expressing siRNA
    Pedro E Cruz
    Department of Pediatrics, University of Florida, Gainesville, FL, USA
    Lab Invest 87:893-902. 2007
    ..The rAAV8-3X-siRNA vector may hold promise as a potential therapy for patients with AAT liver disease...
  42. ncbi Viral vector-mediated and cell-based therapies for treatment of cystic fibrosis
    Terence R Flotte
    Department of Pediatrics, University of Florida, Gainesville, Florida, USA
    Mol Ther 15:229-41. 2007
    ..This article will review the advancements made and challenges remaining in the development of viral vector-mediated and cell-based approaches to treat patients with CF...
  43. ncbi Preclinical characterization of a recombinant adeno-associated virus type 1-pseudotyped vector demonstrates dose-dependent injection site inflammation and dissemination of vector genomes to distant sites
    Terence R Flotte
    Powell Gene Therapy Center, Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA
    Hum Gene Ther 18:245-56. 2007
    ..The copy number of vector DNA in the blood and semen declined over time throughout the study. These two dose-dependent findings have served to guide to the design of a phase 1 human trial of rAAV1-AAT...
  44. ncbi Gene therapy for pyruvate dehydrogenase E1alpha deficiency using recombinant adeno-associated virus 2 (rAAV2) vectors
    Renius Owen
    Department of Pediatrics, the General Clinical Research Center, University of Florida, Gainesville, Florida 32610, USA
    Mol Ther 6:394-9. 2002
    ..These studies provide the basis for future efforts to develop a recombinant AAV (rAAV)-based gene therapy approach for the correction of PDC deficiency...
  45. ncbi Recombinant adeno-associated virus-mediated global anterograde delivery of glial cell line-derived neurotrophic factor to the spinal cord: comparison of rubrospinal and corticospinal tracts in the rat
    Kevin D Foust
    Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32611, USA
    Hum Gene Ther 19:71-82. 2008
    ..Spinal cord GDNF levels were elevated at distances up to 72 mm from the injection sites, and confirmed that RST-related GDNF transport to spinal cord surpassed CST-associated delivery...
  46. ncbi Improved method of recombinant AAV2 delivery for systemic targeted gene therapy
    Cathryn Mah
    Department of Pediatrics, University of Florida, Gainesville, Florida 32610, USA
    Mol Ther 6:106-12. 2002
    ..These studies demonstrate a novel method to deliver rAAV vectors more effectively that could prove to be a successful alternative mode of virus-mediated human gene therapy...
  47. ncbi Immune responses to recombinant adeno-associated virus vectors: putting preclinical findings into perspective
    Terence R Flotte
    Department of Pediatrics and Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610-0296, USA
    Hum Gene Ther 15:716-7. 2004
  48. ncbi Correlation between DNA transfer and cystic fibrosis airway epithelial cell correction after recombinant adeno-associated virus serotype 2 gene therapy
    Terence R Flotte
    Department of Pediatrics, University of Florida, Gainesville, 32610, USA
    Hum Gene Ther 16:921-8. 2005
    ..The observation of sizeable physiological correction in the face of low mRNA levels may reflect the regulatory role of low levels of CFTR protein as an activator of other chloride channels...
  49. ncbi Effects of CFTR, interleukin-10, and Pseudomonas aeruginosa on gene expression profiles in a CF bronchial epithelial cell Line
    Isabel Virella-Lowell
    Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29401, USA
    Mol Ther 10:562-73. 2004
    ..In conclusion, the CFTR genotype changes the expression of multiple genes at baseline and in response to bacterial challenge, and only a subset of these changes is secondary to IL-10 deficiency...
  50. ncbi Ex vivo transduced liver progenitor cells as a platform for gene therapy in mice
    Sihong Song
    Department of Pharmaceutics, University of Florida, Gainesville, FL 32610, USA
    Hepatology 40:918-24. 2004
    ....
  51. ncbi Methylphenidate does not improve cognitive function in healthy sleep-deprived young adults
    Christopher L Bray
    University of Florida College of Medicine, Gainesville, FL 32610 1042, USA
    J Investig Med 52:192-201. 2004
    ..Abuse of methylphenidate, a treatment of attention-deficit/hyperactivity disorder, is reported to be increasing among students for the purpose of improving cognition...
  52. ncbi Adeno-associated virus-mediated gene transfer for lung diseases
    Terence R Flotte
    Powell Gene Therapy Center, Genetics Institute, and Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA
    Hum Gene Ther 16:643-8. 2005
  53. ncbi DNA-dependent PK inhibits adeno-associated virus DNA integration
    Sihong Song
    Department of Pharmaceutics, Powell Gene Therapy Center, Genetics Institute, University of Florida, Gainesville, FL 32610, USA
    Proc Natl Acad Sci U S A 101:2112-6. 2004
    ..In summary, we have provided evidence that DNA-PK inhibits AAV integration both in vitro and in vivo...
  54. ncbi The promise of gene therapy for the treatment of alpha-1 antitrypsin deficiency
    Pedro E Cruz
    University of Florida, Nephrology Division, College of Medicine, FL, USA
    Pharmacogenomics 8:1191-8. 2007
    ..The last two trials delivered recombinant adeno-associated vectors encoding the alpha-1 antitrypsin cDNA by intramuscular injection. In this review, the progress of ongoing clinical trials and new gene therapy technologies is discussed...
  55. ncbi 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
    William W Hauswirth
    Department of Ophthalmology, University of Florida, Gainesville, FL 32610, USA
    Hum Gene Ther 19:979-90. 2008
    ..99). Comparisons are drawn between the present work and two other studies of ocular gene therapy for RPE65-LCA that were carried out contemporaneously and reported...
  56. ncbi Adeno-associated viral vectors for CF gene therapy
    Terence R Flotte
    Powell Gene Therapy Center, University of Florida, Gainesville, FL, USA
    Methods Mol Med 70:599-608. 2002
  57. ncbi Herpesvirus-based infectious titering of recombinant adeno-associated viral vectors
    Imran Mohiuddin
    Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610-0266, USA
    Mol Ther 11:320-6. 2005
    ..These methods generate reliable infectious titers for AAV vectors of different serotypes, thus enhancing product characterization and reducing risk in future clinical applications...
  58. ncbi Transduction of human and mouse pancreatic islet cells using a bicistronic recombinant adeno-associated viral vector
    Matthias Kapturczak
    Department of Medicine, University of Florida, Gainesville, Florida 32610, USA
    Mol Ther 5:154-60. 2002
    ..These data are the first report of efficient islet cell transduction with two genes using a single bicistronic rAAV vector and have direct implications for strategies aimed at enhancing islet transplant survival...
  59. ncbi Enhanced IgE allergic response to Aspergillus fumigatus in CFTR-/- mice
    Christian Muller
    Department of Pediatrics, Center for Immunology and Transplantation and Genetics Institute, University of Florida College of Medicine, Gainesville, FL 32610 0296, USA
    Lab Invest 86:130-40. 2006
    ..This system models a very specific type of airway inflammation in CF and could provide insights into pathogenesis and treatment of the disease...
  60. ncbi Cystic fibrosis transmembrane conductance regulator deficiency exacerbates islet cell dysfunction after beta-cell injury
    Michael S Stalvey
    Department of Pathology, University of Florida, College of Medicine, PO Box 100275, Gainesville, FL 32610, USA
    Diabetes 55:1939-45. 2006
    ..These studies suggest metabolic derangements in CFRD originate from an islet dysfunction inherent to the CFTR(-/-) state...
  61. ncbi Targeting recombinant adeno-associated virus vectors to enhance gene transfer to pancreatic islets and liver
    S A Loiler
    Department of Pediatrics, Pathology, Medicine, and Molecular Genetics and Microbiology, University of Florida Genetics Institute, Gainesville, FL 32610, USA
    Gene Ther 10:1551-8. 2003
    ..The use of receptor-targeted rAAV particles may circumvent the lower abundance of receptors on certain nonpermissive cell types...
  62. ncbi Towards a rAAV-based gene therapy for ADA-SCID: from ADA deficiency to current and future treatment strategies
    Jared N Silver
    University of Florida College of Medicine, Department of Pediatrics, Gainesville, FL 32607, USA
    Pharmacogenomics 9:947-68. 2008
    ..This review endeavors to describe ADA-SCID, the traditional treatments, previous retroviral gene therapies, and primarily, alternative recombinant adeno-associated virus-based strategies to remedy this potentially fatal genetic disease...
  63. ncbi IL-10 regulation of lupus in the NZM2410 murine model
    Kim R M Blenman
    Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32601-0275, USA
    Lab Invest 86:1136-48. 2006
    ..These results also reinforce the notion that IL-10 exerts multiple functions and commend caution in equating high levels of IL-10 and increased pathogenesis in systemic autoimmunity...
  64. ncbi Defective acid sphingomyelinase pathway with Pseudomonas aeruginosa infection in cystic fibrosis
    Hong Yu
    Department of Pediatrics, Medical University of South Carolina, 173 Ashley BSB 749, Charleston, SC 29403, USA
    Am J Respir Cell Mol Biol 41:367-75. 2009
    ..aeruginosa infection. This study demonstrates that the defective ASMase pathway in CF is a key contributor to the unabated IL-8 response with P. aeruginosa infection and to the compromised host response failing to eradicate bacteria...
  65. ncbi Murine model for cystic fibrosis bone disease demonstrates osteopenia and sex-related differences in bone formation
    Troy D Pashuck
    Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida 32610, USA
    Pediatr Res 65:311-6. 2009
    ..This proanabolic observation in male CF mice is consistent with other clinical sex differences in CF...
  66. ncbi CFTR mutations impart elevated immune reactivity in a murine model of cystic fibrosis related diabetes
    Michael S Stalvey
    Department of Pediatrics, University of Florida, College of Medicine, P O Box 100296, Gainesville, FL 32610, USA
    Cytokine 44:154-9. 2008
    ..These results suggest that, hyperglycemia may exacerbate the clinical course in CF by impacting immune reactivity. There is clear need to maximize metabolic management in CFRD...
  67. ncbi Approaches and limitations to gene therapy for mitochondrial diseases
    R Owen
    Powell Gene Therapy Center, University of Florida Genetics Institute, Gainesville 32610-0266, USA
    Antioxid Redox Signal 3:451-60. 2001
    ..Therefore, gene therapy must be considered as a possible alternative. In this review, we will discuss the possibilities and the problems associated with gene therapy for mitochondrial disorders...
  68. ncbi Virus-based gene delivery systems
    Cathryn Mah
    Powell Gene Therapy Center, University of Florida, Gainesville, Florida 32610-0266, USA
    Clin Pharmacokinet 41:901-11. 2002
    ..This review will also illustrate several current improved physical delivery systems for optimal vector administration...
  69. ncbi Gene therapy: the first two decades and the current state-of-the-art
    Terence R Flotte
    Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA
    J Cell Physiol 213:301-5. 2007
    ....
  70. ncbi Functional expression of the single subunit NADH dehydrogenase in mitochondria in vivo: a potential therapy for complex I deficiencies
    Byoung Boo Seo
    Division of Biochemistry, Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA
    Hum Gene Ther 15:887-95. 2004
    ..The data indicate that the NDI1 gene will be a promising therapeutic tool in the treatment of encephalomyopathies and neurodegenerative diseases caused by complex I impairments...
  71. ncbi Biochemical correction of short-chain acyl-coenzyme A dehydrogenase deficiency after portal vein injection of rAAV8-SCAD
    Stuart G Beattie
    University of Massachusetts Medical School, Worcester, MA 01655, USA
    Hum Gene Ther 19:579-88. 2008
    ..These results demonstrate biochemical correction of SCAD deficiency after AAV8-mediated SCAD gene delivery...
  72. ncbi In utero efficacy of cystic fibrosis gene therapy: difficult studies, positive or negative
    Terence R Flotte
    University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA
    Mol Ther 16:806-7. 2008
  73. ncbi A phase II, double-blind, randomized, placebo-controlled clinical trial of tgAAVCF using maxillary sinus delivery in patients with cystic fibrosis with antrostomies
    John A Wagner
    Department of Molecular Pharmacology, Stanford CCSR Building, Stanford, CA 94305-5174, USA
    Hum Gene Ther 13:1349-59. 2002
    ..In summary, this Phase II trial confirms the safety of tgAAVCF but provides little support of its efficacy in the within-patient controlled sinus study. Various potentially confounding factors are discussed...
  74. ncbi The short apical membrane half-life of rescued {Delta}F508-cystic fibrosis transmembrane conductance regulator (CFTR) results from accelerated endocytosis of {Delta}F508-CFTR in polarized human airway epithelial cells
    Agnieszka Swiatecka-Urban
    Department of Physiology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 280:36762-72. 2005
    ....
  75. ncbi Efficient transduction of vascular endothelial cells with recombinant adeno-associated virus serotype 1 and 5 vectors
    Sifeng Chen
    Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Hum Gene Ther 16:235-47. 2005
    ..These results suggest the unique potential of rAAV1 and rAAV5-based vectors for vascular-targeted gene-based therapeutic strategies...
  76. ncbi Interleukin 10 attenuates neointimal proliferation and inflammation in aortic allografts by a heme oxygenase-dependent pathway
    Sifeng Chen
    Department of Medicine, Nephrology Research and Training Center, University of Alabama at Birmingham, Birmingham, AL 35294
    Proc Natl Acad Sci U S A 102:7251-6. 2005
    ....
  77. ncbi Safety of recombinant adeno-associated virus type 2-RPE65 vector delivered by ocular subretinal injection
    Samuel G Jacobson
    Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Ther 13:1074-84. 2006
    ..5-log unit range of vector doses proved efficacious. The efficacy and toxicity limits defined in this study lead to suggestions for the design of a subretinal AAV-2/2.RPE65 human trial of RPE65-associated LCA...
  78. ncbi alpha-1 antitrypsin inhibits caspase-3 activity, preventing lung endothelial cell apoptosis
    Irina Petrache
    Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Am J Pathol 169:1155-66. 2006
    ....
  79. ncbi Enhancing rAAV vector expression in the lung
    Isabel Virella-Lowell
    Department of Pediatrics of the University of Florida College of Medicine, USA
    J Gene Med 7:842-50. 2005
    ..Although the advantage of rAAV5 over rAAV2 in the lung has already been described, the availability of another serotype (rAAV1) capable of efficient gene transfer in the lung could be useful...
  80. ncbi Controlling neuropathic pain by adeno-associated virus driven production of the anti-inflammatory cytokine, interleukin-10
    Erin D Milligan
    Department of Psychology and the Center for Neuroscience, University of CO at Boulder, Boulder, CO 80309 USA
    Mol Pain 1:9. 2005
    ..Taken together, these data provide initial support that intrathecal gene therapy to drive the production of IL-10 may prove to be an efficacious treatment for neuropathic pain...
  81. ncbi Deposition and expression of aerosolized rAAV vectors in the lungs of Rhesus macaques
    Suzanne E Beck
    Eudowood Division of Pediatric Respitarory Sciences and Departments of Pediatrics, and Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Mol Ther 6:546-54. 2002
    ..u. (P=0.030). We conclude that expression of rAAV2-GFP in lungs appears to be related to depositing a regional threshold dose greater than 3 x 10(9) i.u., easily achieved by bronchoscopic microspraying...
  82. ncbi The murine alpha(1)-proteinase inhibitor gene family: polymorphism, chromosomal location, and structure
    Karen W Barbour
    Department of Biological Sciences, University of South Carolina, Columbia, South Carolina, 29208, USA
    Genomics 80:515-22. 2002
    ..Finally, we present the complete sequence of an 84-kb region of Serpina1 containing a tandem repeat of two alpha(1)-PI genes...
  83. ncbi A single-subunit NADH-quinone oxidoreductase renders resistance to mammalian nerve cells against complex I inhibition
    Byoung Boo Seo
    Division of Biochemistry, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA
    Mol Ther 6:336-41. 2002
    ..It is conceivable that the NDI1 gene will be a promising tool in the treatment of neurodegenerative conditions caused by complex I inhibition...
  84. ncbi Successful transgene expression with serial doses of aerosolized rAAV2 vectors in rhesus macaques
    Anne C Fischer
    Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Mol Ther 8:918-26. 2003
    ..This study is the first to demonstrate successful gene transfer subsequent to repeated aerosolized doses of rAAV2 in immunocompetent nonhuman primates without associated inflammatory responses prohibitive to transgene expression...
  85. ncbi Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics
    Artur V Cideciyan
    Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 105:15112-7. 2008
    ..Cone-sensitivity recovery time was rapid. These results demonstrate dramatic, albeit imperfect, recovery of rod- and cone-photoreceptor-based vision after RPE65 gene therapy...
  86. ncbi Safety in nonhuman primates of ocular AAV2-RPE65, a candidate treatment for blindness in Leber congenital amaurosis
    Samuel G Jacobson
    Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Hum Gene Ther 17:845-58. 2006
    ..RPE65. The potential value of foveal treatment for LCA and other retinal degenerations warrants further research into how to achieve gene transfer without retinal injury from surgical detachment of the retina...