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. 1995 Dec;96(6):2547–2554. doi: 10.1172/JCI118318

Gene therapy for cystic fibrosis: challenges and future directions.

J M Wilson 1
PMCID: PMC185958  PMID: 8675618

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Selected References

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  1. Anderson W. F. Prospects for human gene therapy. Science. 1984 Oct 26;226(4673):401–409. doi: 10.1126/science.6093246. [DOI] [PubMed] [Google Scholar]
  2. Ando K., Moriyama T., Guidotti L. G., Wirth S., Schreiber R. D., Schlicht H. J., Huang S. N., Chisari F. V. Mechanisms of class I restricted immunopathology. A transgenic mouse model of fulminant hepatitis. J Exp Med. 1993 Nov 1;178(5):1541–1554. doi: 10.1084/jem.178.5.1541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barasch J., Kiss B., Prince A., Saiman L., Gruenert D., al-Awqati Q. Defective acidification of intracellular organelles in cystic fibrosis. Nature. 1991 Jul 4;352(6330):70–73. doi: 10.1038/352070a0. [DOI] [PubMed] [Google Scholar]
  4. Barr D., Tubb J., Ferguson D., Scaria A., Lieber A., Wilson C., Perkins J., Kay M. A. Strain related variations in adenovirally mediated transgene expression from mouse hepatocytes in vivo: comparisons between immunocompetent and immunodeficient inbred strains. Gene Ther. 1995 Mar;2(2):151–155. [PubMed] [Google Scholar]
  5. Bear C. E., Li C. H., Kartner N., Bridges R. J., Jensen T. J., Ramjeesingh M., Riordan J. R. Purification and functional reconstitution of the cystic fibrosis transmembrane conductance regulator (CFTR). Cell. 1992 Feb 21;68(4):809–818. doi: 10.1016/0092-8674(92)90155-6. [DOI] [PubMed] [Google Scholar]
  6. Berkner K. L. Development of adenovirus vectors for the expression of heterologous genes. Biotechniques. 1988 Jul-Aug;6(7):616–629. [PubMed] [Google Scholar]
  7. Bluestone J. A. New perspectives of CD28-B7-mediated T cell costimulation. Immunity. 1995 Jun;2(6):555–559. doi: 10.1016/1074-7613(95)90000-4. [DOI] [PubMed] [Google Scholar]
  8. Boucher R. C., Knowles M. R., Johnson L. G., Olsen J. C., Pickles R., Wilson J. M., Engelhardt J., Yang Y., Grossman M. Gene therapy for cystic fibrosis using E1-deleted adenovirus: a phase I trial in the nasal cavity. The University of North Carolina at Chapel Hill. Hum Gene Ther. 1994 May;5(5):615–639. doi: 10.1089/hum.1994.5.5-615. [DOI] [PubMed] [Google Scholar]
  9. Bout A., Perricaudet M., Baskin G., Imler J. L., Scholte B. J., Pavirani A., Valerio D. Lung gene therapy: in vivo adenovirus-mediated gene transfer to rhesus monkey airway epithelium. Hum Gene Ther. 1994 Jan;5(1):3–10. doi: 10.1089/hum.1994.5.1-3. [DOI] [PubMed] [Google Scholar]
  10. Brody S. L., Metzger M., Danel C., Rosenfeld M. A., Crystal R. G. Acute responses of non-human primates to airway delivery of an adenovirus vector containing the human cystic fibrosis transmembrane conductance regulator cDNA. Hum Gene Ther. 1994 Jul;5(7):821–836. doi: 10.1089/hum.1994.5.7-821. [DOI] [PubMed] [Google Scholar]
  11. Caplen N. J., Alton E. W., Middleton P. G., Dorin J. R., Stevenson B. J., Gao X., Durham S. R., Jeffery P. K., Hodson M. E., Coutelle C. Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Nat Med. 1995 Jan;1(1):39–46. doi: 10.1038/nm0195-39. [DOI] [PubMed] [Google Scholar]
  12. Cheng P. W., Boat T. F., Cranfill K., Yankaskas J. R., Boucher R. C. Increased sulfation of glycoconjugates by cultured nasal epithelial cells from patients with cystic fibrosis. J Clin Invest. 1989 Jul;84(1):68–72. doi: 10.1172/JCI114171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Cheng S. H., Rich D. P., Marshall J., Gregory R. J., Welsh M. J., Smith A. E. Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel. Cell. 1991 Sep 6;66(5):1027–1036. doi: 10.1016/0092-8674(91)90446-6. [DOI] [PubMed] [Google Scholar]
  14. Crystal R. G., Jaffe A., Brody S., Mastrangeli A., McElvaney N. G., Rosenfeld M., Chu C. S., Danel C., Hay J., Eissa T. A phase 1 study, in cystic fibrosis patients, of the safety, toxicity, and biological efficacy of a single administration of a replication deficient, recombinant adenovirus carrying the cDNA of the normal cystic fibrosis transmembrane conductance regulator gene in the lung. Hum Gene Ther. 1995 May;6(5):643–666. doi: 10.1089/hum.1995.6.5-643. [DOI] [PubMed] [Google Scholar]
  15. Crystal R. G., McElvaney N. G., Rosenfeld M. A., Chu C. S., Mastrangeli A., Hay J. G., Brody S. L., Jaffe H. A., Eissa N. T., Danel C. Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis. Nat Genet. 1994 Sep;8(1):42–51. doi: 10.1038/ng0994-42. [DOI] [PubMed] [Google Scholar]
  16. Drumm M. L., Pope H. A., Cliff W. H., Rommens J. M., Marvin S. A., Tsui L. C., Collins F. S., Frizzell R. A., Wilson J. M. Correction of the cystic fibrosis defect in vitro by retrovirus-mediated gene transfer. Cell. 1990 Sep 21;62(6):1227–1233. doi: 10.1016/0092-8674(90)90398-x. [DOI] [PubMed] [Google Scholar]
  17. Drumm M. L., Wilkinson D. J., Smit L. S., Worrell R. T., Strong T. V., Frizzell R. A., Dawson D. C., Collins F. S. Chloride conductance expressed by delta F508 and other mutant CFTRs in Xenopus oocytes. Science. 1991 Dec 20;254(5039):1797–1799. doi: 10.1126/science.1722350. [DOI] [PubMed] [Google Scholar]
  18. Durie F. H., Foy T. M., Masters S. R., Laman J. D., Noelle R. J. The role of CD40 in the regulation of humoral and cell-mediated immunity. Immunol Today. 1994 Sep;15(9):406–411. doi: 10.1016/0167-5699(94)90269-0. [DOI] [PubMed] [Google Scholar]
  19. Engelhardt J. F., Litzky L., Wilson J. M. Prolonged transgene expression in cotton rat lung with recombinant adenoviruses defective in E2a. Hum Gene Ther. 1994 Oct;5(10):1217–1229. doi: 10.1089/hum.1994.5.10-1217. [DOI] [PubMed] [Google Scholar]
  20. Engelhardt J. F., Simon R. H., Yang Y., Zepeda M., Weber-Pendleton S., Doranz B., Grossman M., Wilson J. M. Adenovirus-mediated transfer of the CFTR gene to lung of nonhuman primates: biological efficacy study. Hum Gene Ther. 1993 Dec;4(6):759–769. doi: 10.1089/hum.1993.4.6-759. [DOI] [PubMed] [Google Scholar]
  21. Engelhardt J. F., Yang Y., Stratford-Perricaudet L. D., Allen E. D., Kozarsky K., Perricaudet M., Yankaskas J. R., Wilson J. M. Direct gene transfer of human CFTR into human bronchial epithelia of xenografts with E1-deleted adenoviruses. Nat Genet. 1993 May;4(1):27–34. doi: 10.1038/ng0593-27. [DOI] [PubMed] [Google Scholar]
  22. Engelhardt J. F., Yankaskas J. R., Ernst S. A., Yang Y., Marino C. R., Boucher R. C., Cohn J. A., Wilson J. M. Submucosal glands are the predominant site of CFTR expression in the human bronchus. Nat Genet. 1992 Nov;2(3):240–248. doi: 10.1038/ng1192-240. [DOI] [PubMed] [Google Scholar]
  23. Engelhardt J. F., Zepeda M., Cohn J. A., Yankaskas J. R., Wilson J. M. Expression of the cystic fibrosis gene in adult human lung. J Clin Invest. 1994 Feb;93(2):737–749. doi: 10.1172/JCI117028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Fellous M., Nir U., Wallach D., Merlin G., Rubinstein M., Revel M. Interferon-dependent induction of mRNA for the major histocompatibility antigens in human fibroblasts and lymphoblastoid cells. Proc Natl Acad Sci U S A. 1982 May;79(10):3082–3086. doi: 10.1073/pnas.79.10.3082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ferkol T., Kaetzel C. S., Davis P. B. Gene transfer into respiratory epithelial cells by targeting the polymeric immunoglobulin receptor. J Clin Invest. 1993 Nov;92(5):2394–2400. doi: 10.1172/JCI116845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Flotte T. R., Afione S. A., Conrad C., McGrath S. A., Solow R., Oka H., Zeitlin P. L., Guggino W. B., Carter B. J. Stable in vivo expression of the cystic fibrosis transmembrane conductance regulator with an adeno-associated virus vector. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10613–10617. doi: 10.1073/pnas.90.22.10613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Foskett J. K., Wong D. C. [Ca2+]i inhibition of Ca2+ release-activated Ca2+ influx underlies agonist- and thapsigargin-induced [Ca2+]i oscillations in salivary acinar cells. J Biol Chem. 1994 Dec 16;269(50):31525–31532. [PubMed] [Google Scholar]
  28. Gabriel S. E., Clarke L. L., Boucher R. C., Stutts M. J. CFTR and outward rectifying chloride channels are distinct proteins with a regulatory relationship. Nature. 1993 May 20;363(6426):263–268. doi: 10.1038/363263a0. [DOI] [PubMed] [Google Scholar]
  29. Gan K. H., Veeze H. J., van den Ouweland A. M., Halley D. J., Scheffer H., van der Hout A., Overbeek S. E., de Jongste J. C., Bakker W., Heijerman H. G. A cystic fibrosis mutation associated with mild lung disease. N Engl J Med. 1995 Jul 13;333(2):95–99. doi: 10.1056/NEJM199507133330204. [DOI] [PubMed] [Google Scholar]
  30. Ginsberg H. S., Horswood R. L., Chanock R. M., Prince G. A. Role of early genes in pathogenesis of adenovirus pneumonia. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6191–6195. doi: 10.1073/pnas.87.16.6191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ginsberg H. S., Moldawer L. L., Sehgal P. B., Redington M., Kilian P. L., Chanock R. M., Prince G. A. A mouse model for investigating the molecular pathogenesis of adenovirus pneumonia. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1651–1655. doi: 10.1073/pnas.88.5.1651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Goldman M. J., Litzky L. A., Engelhardt J. F., Wilson J. M. Transfer of the CFTR gene to the lung of nonhuman primates with E1-deleted, E2a-defective recombinant adenoviruses: a preclinical toxicology study. Hum Gene Ther. 1995 Jul;6(7):839–851. doi: 10.1089/hum.1995.6.7-839. [DOI] [PubMed] [Google Scholar]
  33. Goldman M. J., Wilson J. M. Expression of alpha v beta 5 integrin is necessary for efficient adenovirus-mediated gene transfer in the human airway. J Virol. 1995 Oct;69(10):5951–5958. doi: 10.1128/jvi.69.10.5951-5958.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Goldman M. J., Yang Y., Wilson J. M. Gene therapy in a xenograft model of cystic fibrosis lung corrects chloride transport more effectively than the sodium defect. Nat Genet. 1995 Feb;9(2):126–131. doi: 10.1038/ng0295-126. [DOI] [PubMed] [Google Scholar]
  35. Graham F. L., Smiley J., Russell W. C., Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol. 1977 Jul;36(1):59–74. doi: 10.1099/0022-1317-36-1-59. [DOI] [PubMed] [Google Scholar]
  36. Grubb B. R., Pickles R. J., Ye H., Yankaskas J. R., Vick R. N., Engelhardt J. F., Wilson J. M., Johnson L. G., Boucher R. C. Inefficient gene transfer by adenovirus vector to cystic fibrosis airway epithelia of mice and humans. Nature. 1994 Oct 27;371(6500):802–806. doi: 10.1038/371802a0. [DOI] [PubMed] [Google Scholar]
  37. Grubb B. R., Vick R. N., Boucher R. C. Hyperabsorption of Na+ and raised Ca(2+)-mediated Cl- secretion in nasal epithelia of CF mice. Am J Physiol. 1994 May;266(5 Pt 1):C1478–C1483. doi: 10.1152/ajpcell.1994.266.5.C1478. [DOI] [PubMed] [Google Scholar]
  38. Issekutz T. B., Stoltz J. M., vd Meide P. Lymphocyte recruitment in delayed-type hypersensitivity. The role of IFN-gamma. J Immunol. 1988 May 1;140(9):2989–2993. [PubMed] [Google Scholar]
  39. Johnson L. G., Olsen J. C., Sarkadi B., Moore K. L., Swanstrom R., Boucher R. C. Efficiency of gene transfer for restoration of normal airway epithelial function in cystic fibrosis. Nat Genet. 1992 Sep;2(1):21–25. doi: 10.1038/ng0992-21. [DOI] [PubMed] [Google Scholar]
  40. Jones T. R., Hanson L. K., Sun L., Slater J. S., Stenberg R. M., Campbell A. E. Multiple independent loci within the human cytomegalovirus unique short region down-regulate expression of major histocompatibility complex class I heavy chains. J Virol. 1995 Aug;69(8):4830–4841. doi: 10.1128/jvi.69.8.4830-4841.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Kartner N., Hanrahan J. W., Jensen T. J., Naismith A. L., Sun S. Z., Ackerley C. A., Reyes E. F., Tsui L. C., Rommens J. M., Bear C. E. Expression of the cystic fibrosis gene in non-epithelial invertebrate cells produces a regulated anion conductance. Cell. 1991 Feb 22;64(4):681–691. doi: 10.1016/0092-8674(91)90498-n. [DOI] [PubMed] [Google Scholar]
  42. Kerem B., Rommens J. M., Buchanan J. A., Markiewicz D., Cox T. K., Chakravarti A., Buchwald M., Tsui L. C. Identification of the cystic fibrosis gene: genetic analysis. Science. 1989 Sep 8;245(4922):1073–1080. doi: 10.1126/science.2570460. [DOI] [PubMed] [Google Scholar]
  43. Khan T. Z., Wagener J. S., Bost T., Martinez J., Accurso F. J., Riches D. W. Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med. 1995 Apr;151(4):1075–1082. doi: 10.1164/ajrccm/151.4.1075. [DOI] [PubMed] [Google Scholar]
  44. Knowles M. R., Hohneker K. W., Zhou Z., Olsen J. C., Noah T. L., Hu P. C., Leigh M. W., Engelhardt J. F., Edwards L. J., Jones K. R. A controlled study of adenoviral-vector-mediated gene transfer in the nasal epithelium of patients with cystic fibrosis. N Engl J Med. 1995 Sep 28;333(13):823–831. doi: 10.1056/NEJM199509283331302. [DOI] [PubMed] [Google Scholar]
  45. Kohn D. B., Weinberg K. I., Nolta J. A., Heiss L. N., Lenarsky C., Crooks G. M., Hanley M. E., Annett G., Brooks J. S., el-Khoureiy A. Engraftment of gene-modified umbilical cord blood cells in neonates with adenosine deaminase deficiency. Nat Med. 1995 Oct;1(10):1017–1023. doi: 10.1038/nm1095-1017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Maraskovsky E., Chen W. F., Shortman K. IL-2 and IFN-gamma are two necessary lymphokines in the development of cytolytic T cells. J Immunol. 1989 Aug 15;143(4):1210–1214. [PubMed] [Google Scholar]
  47. Mastrangeli A., Danel C., Rosenfeld M. A., Stratford-Perricaudet L., Perricaudet M., Pavirani A., Lecocq J. P., Crystal R. G. Diversity of airway epithelial cell targets for in vivo recombinant adenovirus-mediated gene transfer. J Clin Invest. 1993 Jan;91(1):225–234. doi: 10.1172/JCI116175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Mitani K., Graham F. L., Caskey C. T., Kochanek S. Rescue, propagation, and partial purification of a helper virus-dependent adenovirus vector. Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3854–3858. doi: 10.1073/pnas.92.9.3854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Paul W. E., Seder R. A. Lymphocyte responses and cytokines. Cell. 1994 Jan 28;76(2):241–251. doi: 10.1016/0092-8674(94)90332-8. [DOI] [PubMed] [Google Scholar]
  50. Prince G. A., Porter D. D., Jenson A. B., Horswood R. L., Chanock R. M., Ginsberg H. S. Pathogenesis of adenovirus type 5 pneumonia in cotton rats (Sigmodon hispidus). J Virol. 1993 Jan;67(1):101–111. doi: 10.1128/jvi.67.1.101-111.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Quinton P. M. Chloride impermeability in cystic fibrosis. Nature. 1983 Feb 3;301(5899):421–422. doi: 10.1038/301421a0. [DOI] [PubMed] [Google Scholar]
  52. Rich D. P., Anderson M. P., Gregory R. J., Cheng S. H., Paul S., Jefferson D. M., McCann J. D., Klinger K. W., Smith A. E., Welsh M. J. Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells. Nature. 1990 Sep 27;347(6291):358–363. doi: 10.1038/347358a0. [DOI] [PubMed] [Google Scholar]
  53. Riordan J. R., Rommens J. M., Kerem B., Alon N., Rozmahel R., Grzelczak Z., Zielenski J., Lok S., Plavsic N., Chou J. L. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989 Sep 8;245(4922):1066–1073. doi: 10.1126/science.2475911. [DOI] [PubMed] [Google Scholar]
  54. Rommens J. M., Iannuzzi M. C., Kerem B., Drumm M. L., Melmer G., Dean M., Rozmahel R., Cole J. L., Kennedy D., Hidaka N. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989 Sep 8;245(4922):1059–1065. doi: 10.1126/science.2772657. [DOI] [PubMed] [Google Scholar]
  55. Rosenfeld M. A., Siegfried W., Yoshimura K., Yoneyama K., Fukayama M., Stier L. E., Päkkö P. K., Gilardi P., Stratford-Perricaudet L. D., Perricaudet M. Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo. Science. 1991 Apr 19;252(5004):431–434. doi: 10.1126/science.2017680. [DOI] [PubMed] [Google Scholar]
  56. Rosenfeld M. A., Yoshimura K., Trapnell B. C., Yoneyama K., Rosenthal E. R., Dalemans W., Fukayama M., Bargon J., Stier L. E., Stratford-Perricaudet L. In vivo transfer of the human cystic fibrosis transmembrane conductance regulator gene to the airway epithelium. Cell. 1992 Jan 10;68(1):143–155. doi: 10.1016/0092-8674(92)90213-v. [DOI] [PubMed] [Google Scholar]
  57. Schwiebert E. M., Egan M. E., Hwang T. H., Fulmer S. B., Allen S. S., Cutting G. R., Guggino W. B. CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP. Cell. 1995 Jun 30;81(7):1063–1073. doi: 10.1016/s0092-8674(05)80011-x. [DOI] [PubMed] [Google Scholar]
  58. Simon R. H., Engelhardt J. F., Yang Y., Zepeda M., Weber-Pendleton S., Grossman M., Wilson J. M. Adenovirus-mediated transfer of the CFTR gene to lung of nonhuman primates: toxicity study. Hum Gene Ther. 1993 Dec;4(6):771–780. doi: 10.1089/hum.1993.4.6-771. [DOI] [PubMed] [Google Scholar]
  59. Skoskiewicz M. J., Colvin R. B., Schneeberger E. E., Russell P. S. Widespread and selective induction of major histocompatibility complex-determined antigens in vivo by gamma interferon. J Exp Med. 1985 Nov 1;162(5):1645–1664. doi: 10.1084/jem.162.5.1645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Sturgess J., Imrie J. Quantitative evaluation of the development of tracheal submucosal glands in infants with cystic fibrosis and control infants. Am J Pathol. 1982 Mar;106(3):303–311. [PMC free article] [PubMed] [Google Scholar]
  61. Stutts M. J., Canessa C. M., Olsen J. C., Hamrick M., Cohn J. A., Rossier B. C., Boucher R. C. CFTR as a cAMP-dependent regulator of sodium channels. Science. 1995 Aug 11;269(5225):847–850. doi: 10.1126/science.7543698. [DOI] [PubMed] [Google Scholar]
  62. Trapnell B. C., Chu C. S., Paakko P. K., Banks T. C., Yoshimura K., Ferrans V. J., Chernick M. S., Crystal R. G. Expression of the cystic fibrosis transmembrane conductance regulator gene in the respiratory tract of normal individuals and individuals with cystic fibrosis. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6565–6569. doi: 10.1073/pnas.88.15.6565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Welsh M. J., Smith A. E., Zabner J., Rich D. P., Graham S. M., Gregory R. J., Pratt B. M., Moscicki R. A. Cystic fibrosis gene therapy using an adenovirus vector: in vivo safety and efficacy in nasal epithelium. Hum Gene Ther. 1994 Feb;5(2):209–219. doi: 10.1089/hum.1994.5.2-209. [DOI] [PubMed] [Google Scholar]
  64. Wickham T. J., Mathias P., Cheresh D. A., Nemerow G. R. Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell. 1993 Apr 23;73(2):309–319. doi: 10.1016/0092-8674(93)90231-e. [DOI] [PubMed] [Google Scholar]
  65. Wille A., Gessner A., Lother H., Lehmann-Grube F. Mechanism of recovery from acute virus infection. VIII. Treatment of lymphocytic choriomeningitis virus-infected mice with anti-interferon-gamma monoclonal antibody blocks generation of virus-specific cytotoxic T lymphocytes and virus elimination. Eur J Immunol. 1989 Jul;19(7):1283–1288. doi: 10.1002/eji.1830190720. [DOI] [PubMed] [Google Scholar]
  66. Wilson J. M., Engelhardt J. F., Grossman M., Simon R. H., Yang Y. Gene therapy of cystic fibrosis lung disease using E1 deleted adenoviruses: a phase I trial. Hum Gene Ther. 1994 Apr;5(4):501–519. doi: 10.1089/hum.1994.5.4-501. [DOI] [PubMed] [Google Scholar]
  67. Wold W. S., Gooding L. R. Region E3 of adenovirus: a cassette of genes involved in host immunosurveillance and virus-cell interactions. Virology. 1991 Sep;184(1):1–8. doi: 10.1016/0042-6822(91)90815-s. [DOI] [PubMed] [Google Scholar]
  68. Yang Y., Engelhardt J. F., Wilson J. M. Ultrastructural localization of variant forms of cystic fibrosis transmembrane conductance regulator in human bronchial epithelial of xenografts. Am J Respir Cell Mol Biol. 1994 Jul;11(1):7–15. doi: 10.1165/ajrcmb.11.1.7517144. [DOI] [PubMed] [Google Scholar]
  69. Yang Y., Li Q., Ertl H. C., Wilson J. M. Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses. J Virol. 1995 Apr;69(4):2004–2015. doi: 10.1128/jvi.69.4.2004-2015.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Yang Y., Nunes F. A., Berencsi K., Gönczöl E., Engelhardt J. F., Wilson J. M. Inactivation of E2a in recombinant adenoviruses improves the prospect for gene therapy in cystic fibrosis. Nat Genet. 1994 Jul;7(3):362–369. doi: 10.1038/ng0794-362. [DOI] [PubMed] [Google Scholar]
  71. Yang Y., Trinchieri G., Wilson J. M. Recombinant IL-12 prevents formation of blocking IgA antibodies to recombinant adenovirus and allows repeated gene therapy to mouse lung. Nat Med. 1995 Sep;1(9):890–893. doi: 10.1038/nm0995-890. [DOI] [PubMed] [Google Scholar]
  72. Yang Y., Wilson J. M. Clearance of adenovirus-infected hepatocytes by MHC class I-restricted CD4+ CTLs in vivo. J Immunol. 1995 Sep 1;155(5):2564–2570. [PubMed] [Google Scholar]
  73. Yang Y., Xiang Z., Ertl H. C., Wilson J. M. Upregulation of class I major histocompatibility complex antigens by interferon gamma is necessary for T-cell-mediated elimination of recombinant adenovirus-infected hepatocytes in vivo. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7257–7261. doi: 10.1073/pnas.92.16.7257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Yei S., Mittereder N., Tang K., O'Sullivan C., Trapnell B. C. Adenovirus-mediated gene transfer for cystic fibrosis: quantitative evaluation of repeated in vivo vector administration to the lung. Gene Ther. 1994 May;1(3):192–200. [PubMed] [Google Scholar]
  75. Yei S., Mittereder N., Wert S., Whitsett J. A., Wilmott R. W., Trapnell B. C. In vivo evaluation of the safety of adenovirus-mediated transfer of the human cystic fibrosis transmembrane conductance regulator cDNA to the lung. Hum Gene Ther. 1994 Jun;5(6):731–744. doi: 10.1089/hum.1994.5.6-731. [DOI] [PubMed] [Google Scholar]
  76. York I. A., Roop C., Andrews D. W., Riddell S. R., Graham F. L., Johnson D. C. A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes. Cell. 1994 May 20;77(4):525–535. doi: 10.1016/0092-8674(94)90215-1. [DOI] [PubMed] [Google Scholar]
  77. Zabner J., Couture L. A., Gregory R. J., Graham S. M., Smith A. E., Welsh M. J. Adenovirus-mediated gene transfer transiently corrects the chloride transport defect in nasal epithelia of patients with cystic fibrosis. Cell. 1993 Oct 22;75(2):207–216. doi: 10.1016/0092-8674(93)80063-k. [DOI] [PubMed] [Google Scholar]
  78. Zabner J., Couture L. A., Smith A. E., Welsh M. J. Correction of cAMP-stimulated fluid secretion in cystic fibrosis airway epithelia: efficiency of adenovirus-mediated gene transfer in vitro. Hum Gene Ther. 1994 May;5(5):585–593. doi: 10.1089/hum.1994.5.5-585. [DOI] [PubMed] [Google Scholar]
  79. Zabner J., Petersen D. M., Puga A. P., Graham S. M., Couture L. A., Keyes L. D., Lukason M. J., St George J. A., Gregory R. J., Smith A. E. Safety and efficacy of repetitive adenovirus-mediated transfer of CFTR cDNA to airway epithelia of primates and cotton rats. Nat Genet. 1994 Jan;6(1):75–83. doi: 10.1038/ng0194-75. [DOI] [PubMed] [Google Scholar]
  80. Zsengeller Z. K., Wert S. E., Hull W. M., Hu X., Yei S., Trapnell B. C., Whitsett J. A. Persistence of replication-deficient adenovirus-mediated gene transfer in lungs of immune-deficient (nu/nu) mice. Hum Gene Ther. 1995 Apr;6(4):457–467. doi: 10.1089/hum.1995.6.4-457. [DOI] [PubMed] [Google Scholar]

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