Gene Therapy: The Advent of Adenovirus

  • Leslie D. Stratford-Perricaudet
  • Michel Perricaudet


Adenovirus has been developed as an alternative gene transfer vehicle which has emerged as a potent vector with a promising future. Infection of cells with replication-incompetent adenoviruses allows the production of foreign proteins encoded by the engineered viruses without otherwise affecting the host cell. Of utmost relevance to gene therapy, postmitotic cells seem particularly adapted to gene transfer by adenovirus, since the viral genome is not integrated into the cell’s chromosome and presumably persists the life of the cell. Administration of recombinant adenoviruses directly in vivo opens the way to new therapeutic strategies. The first successful somatic gene therapy of a hepatic enzyme deficiency in an animal model was achieved using an adenovirus (Stratford-Perricaudet et al., 1990). Since this initial demonstration of the feasibility of correcting a genetic defect with adenovirus, many potential applications have been imagined. The field has aroused much enthousiasm as reflected at the December 1992 RAC meeting where approval was given to carry out clinical trials using three different recombinant adenoviruses capable of expressing the human CFTR, one of which was constructed in our laboratory (Rosenfeld et al., 1992).


Cystic Fibrosis Gene Therapy Cystic Fibrosis Transmembrane Conductance Regulator Duchenne Muscular Dystrophy Recombinant Adenovirus 
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  1. Akli S, Caillaud C, Vigne E, Stratford-Perricaudet LD, Poenaru L, Perricaudet M, Kahn A, Peschanski M (1993): Transfer of foreign genes into the brain using adenovirus vectors. Nature Genetics 3: 224–228PubMedCrossRefGoogle Scholar
  2. Ballay A, Levrero M, Buendia MA, Hollais P, Perricaudet M (1985): In vitro and in vivo synthesis of the hepatitis B virus surface antigen and of the receptor for polymerized human serum albumin from recombinant human adenoviruses. EMBO J 4: 3861–3865PubMedGoogle Scholar
  3. Berkner KL (1988): Development of adenovirus vectors for the expression of heterologous genes. BioTech 6: 616–630CrossRefGoogle Scholar
  4. Berkner KL, Sharp PA (1983): Generation of adenovirus by transfection of Plasmids. Nucl Acids Res 11: 6003–6020PubMedCrossRefGoogle Scholar
  5. Boat TF, Welsh MJ, Beaudet AL (1989): Cystic fibrosis. In: The Metabolic Basis of Inherited Disease, Scriver CR, Beaudet AL, Sly WS, Valle D, eds. NY: McGraw-HillGoogle Scholar
  6. Bout A, Perricaudet M, Baskin G, Imler JL, Schölte BJ, Pavirani A, Valerio D (1993): Lung gene therapy: in vivo adenovirus-mediated gene transfer to rhesus monkey airway epithelium. Hum Gene Ther (In Press)Google Scholar
  7. Brusilow S, Horwich AL (1989): Urea cycle disorders. In: The Metabolic Basis of Inherited Disease, Scriver CR, Beaudet AL, Sly WS, Valle D, eds. NY: McGraw-HillGoogle Scholar
  8. Cavard C, Grimber G, Dubois N, Chassé J-F, Bennoum M, Minet-Thuriaux M, Kamoun P, et Briand P (1988): Correction of mouse ornithine transcarbamylase deficiency by gene transfer into the germ line. Nucl Acids Res 16: 2099–2110PubMedCrossRefGoogle Scholar
  9. Chanock RM, Ludwig L, Heubner RJ, Cate TR, Chu L-W (1966): Immunization by selective infection with type 4 adenovirus grown in human diploid tissue culture. I. Safety and lack of oncogenicity and tests for potency in volunteers. JAMA 195: 445–452PubMedCrossRefGoogle Scholar
  10. Chassé J-F, Perricaudet M, Minet-Thuniaux M, Briand P, Levrero M (1988): Human recombinant adenovirus to correct a mouse enzyme deficiency. J Cell Biochem sup.l2B UCLA Symposium on Molecular and Cellular Biology p. 197Google Scholar
  11. Chassé J-F, Levrero M, Kamoun P, Briand P, Perricaudet M (1989): L’adénovirus: vecteur de thérapie génique. Médecine/Sciences 5: 331–337Google Scholar
  12. Cook JL, May DL, Lewis Jr AM, Walker TA (1987): Adenovirus, El A gene induction of susceptibility to lysis by natural killer cells and activated macrophages in infected rodent cells. J Virol 61: 3510–3520PubMedGoogle Scholar
  13. Drumm ML, Pope HA, Cliff WH, Rommens JM, Marvin SA, Tsui L-C, Collins FS, Frizzell RA, Wilson JM (1990): Correction of the cystic fibrosis defect in vitro by retrovirus-mediated gene transfer. Cell 62: 1227–1233PubMedCrossRefGoogle Scholar
  14. Eloit M, Gilardi-Hebenstreit P, Torna B, Perricaudet M (1990): Construction of a defective adenovirus vector expressing the Pseudorabies virus glycoprotein gp50 and its use as a live vaccine. J Gen Virol 71: 2425–2431PubMedCrossRefGoogle Scholar
  15. Engelhardt JF, Yankaskas JR, Ernst SA, Yang Y, Marino CR, Boucher RC, Cohn JA, Wilson JM (1992): Submucosal glands are the predominant site of CFTR expression in the human bronchus. Nature Genetics 2: 240–248PubMedCrossRefGoogle Scholar
  16. Flint SJ (1981): Structure and genomic organization of adenoviruses. In: DNA Tumor Viruses,2nd ed., Tooze J, ed. Cold Spring Harbor: Cold Spring Harbor LaboratoryGoogle Scholar
  17. Flint SJ, Broker TR (1981): Lytic Infection by adenoviruses. In: DNA Tumor Viruses, 2nd ed., Tooze J, ed. Cold Spring Harbor: Cold Spring Harbor LaboratoryGoogle Scholar
  18. Ghosh- Choudhury G, Haj-Ahmad Y, Brinkley P, Rudy J, Graham F (1986): Human adenovirus cloning vectors based on infectious bacterial plasmids. Gene 50: 161–171PubMedCrossRefGoogle Scholar
  19. Gilardi P, Courtney M, Pavirani A, Perricaudet M (1990): Expression of human alantitrypsin using a recombinant adenovirus vector. FEBS Letters 267: 60–62PubMedCrossRefGoogle Scholar
  20. Gluzman Y, Reichl H, Solnick D (1982): Helper-free adenovirus type 5 vectors. In Eukaryotic Viral Vectors, Gluzman Y, ed. Cold Spring Harbor: Cold Spring Harbor LaboratoryGoogle Scholar
  21. Graham FL, Smiley J, Russell WC, Nairn R (1977): Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol 36: 59–72PubMedCrossRefGoogle Scholar
  22. Gregory RJ, Cheng SH, Rich DP, Marshall J, Paul S, Hehir K, Ostedgaard L, Klinger KW, Welsh MJ, Smith AE (1990): Expression and characterization of the cystic fibrosis transmembrane conductance regulator. Nature 347: 382–386PubMedCrossRefGoogle Scholar
  23. Hodges PE, Rosenberg LE (1989): The spf-ash mouse: a missense mutation in the ornithine transcarbamylase gene also causes aberrant mRNA splicing. PNAS 86: 4142–4146PubMedCrossRefGoogle Scholar
  24. Horwitz MS (1990): Adenoviruses. In Virology 2nd ed., Fields BN, Knipe DM, eds. New York: Raven PressGoogle Scholar
  25. Johnson LG, Olsen JC, Sarkadi B, Moore KL, Swanstrom R, Boucher RC (1992): Efficiency of gene transfer for restoration of normal airway epithelial function in cystic fibrosis. Nature Genetics 2: 21–25PubMedCrossRefGoogle Scholar
  26. Le Gal La Salle G, Robert J-J, Berrard S, Ridoux V, Stratford-Perricaudet LD, Perricaudet M, Mallet J (1993): An adenovirus vector for gene transfer into neurons and glia in the brain. Science 259: 988–990Google Scholar
  27. Levrero M, Ballay A, Skellekens H, Tiollais P, Perricaudet M (1988): Hepatitis B adenovirus recombinant as a potential live vaccine. In: Proceedings of the 8th International Biotechnology Symposium, Paris, Saint-Just-la-Pendue, France: Imp ChiratGoogle Scholar
  28. Levrero M, Barbant V, Ballay A, Balsamo C, Avantaggiati ML, Natoli G, Skellekens H, Tiollais P, Perricaudet M (1991): Defective and non-defective adenovirus vectors to express foreign genes in vitro and in vivo. Gene 101: 195–202PubMedCrossRefGoogle Scholar
  29. Lübeck MD, Davis AR, Chengalvala M, Natuk RJ, Morin JE, Molnar-Kimber K, Mason BB, Bhat BM, Mizutani S, Hung PP, Purcell RH (1989): Immunogenicity and efficacy testing in chimpanzees of an oral hepatitis B vaccine based on live recombinant adenovirus. PNAS 86: 6763–6767PubMedCrossRefGoogle Scholar
  30. Marchioli CC, Yancey RJ, Petrovskis EA, Timmins JG, Post LE (1987): Evaluation of Pseudorabies virus glycoprotein gp50 as a vaccine for Aujeszky’s disease in mice and swine: expression by vaccinia virus and Chinese hamster ovary cells. J Virol 61: 3977–3982PubMedGoogle Scholar
  31. Mastrangeli A, Danel C, Rosenfeld MA, Stratford-Perricaudet LD, Perricaudet M, Pavirani A, Lecocq J-P, Crystal RG (1993): Diversity of airway epithelial cell targets for in vivo recombinant adenovirus-mediated gene transfer. J Clin Invest 91: 225–234PubMedCrossRefGoogle Scholar
  32. Pääbo S, Bhat BM, Wold WSM, Peterson PA (1987): A short sequence in the COOH-terminus makes an adenovirus membrane glycoprotein a resident of the endoplasmic reticulum. Cell 50: 311–317PubMedCrossRefGoogle Scholar
  33. Perricaudet M, Stratford-Perricaudet LD (1993): Adenovirus-mediated in vivo gene therapy. In: Human Viruses in Gene Therapy, Vos JMH, ed. Durham, NC: Carolina Academic PressGoogle Scholar
  34. Quantin B, Stratford-Perricaudet LD, Tajbakhsh S, Mandel J-L (1992): Adenovirus as an expression vector in muscle cells in vivo. PNAS 89: 2581–2584PubMedCrossRefGoogle Scholar
  35. Ragot T, Eloit M, Perricaudet M (1991): Recombinant El A-defective adenoviruses expressing Pseudorabies and Epstein-Barr virus glycoproteins induce immunological responses as live vaccines in rabbits and mice. In Human Gene Transfer Vol. 219, Cohen-Haguenauer O, Boiron M, eds. Grenoble, France: John Libbey EurotextGoogle Scholar
  36. Ragot T, Finerty S, Watkins PE, Perricaudet M, Morgan AJ (1993a): Replication- defective recombinant adenovirus expressing the EpsteiBarr (EBV) envelope glycoprotein gp340/220 induces protective immunity against EBV-induced lymphomas in the cottontop tamarin. J Gen Virol 74: 501–507PubMedCrossRefGoogle Scholar
  37. Ragot T, Vincent N, Chafey P, Vigne E, Gilgenkrantz H, Couton D, Cartaud J, Briand P, Kaplan J-C, Perricaudet M, Kahn A (1993b): Efficient adenovirus- mediated transfer of a human minidystrophin gene to skeletal muscle of mdx mice. Nature 361: 647–650PubMedCrossRefGoogle Scholar
  38. Rich DP, Anderson MP, Gregory RJ, Cheng SH, Paul S, Jefferson DM, McCann JD, Klinger KW, Smith AE, Welsh MJ (1990): Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride cannel regulation in cystic fibrosis airway epithelial cells. Nature 347: 358–363PubMedCrossRefGoogle Scholar
  39. Riordan JR, Rommens JM, Kerem B-S, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou, J-L, Drumm ML, Iannuzzi MC, Collins FS, Tsui L-C (1989): Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245: 1066–1073PubMedCrossRefGoogle Scholar
  40. Rommens JM, Iannuzzi MC, Kerem B-S, Drumm ML, Melmer G, Dean M, Rozmahel R, Cole JL, Kennedy D, Hidaka N, Zsiga M, Buchwald M, Riordan JR, Tsui L-C, Collins FS (1989): Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 245: 1059–1065PubMedCrossRefGoogle Scholar
  41. Rosenfeld MA, Siegfried W, Yoshimura K, Yoneyama K, Fukayama M, Stier LE, Paako PK, Gilardi P, Stratford-Perricaudet LD, Perricaudet M, Jallat S, Pavirani A, Lecocq J-P, Crystal RG (1991): Adenovirus-mediated transfer of a recombinant al-antitrypsin gene to the lung epithelium in vivo. Science 252: 431–434PubMedCrossRefGoogle Scholar
  42. Rosenfeld MA, Yoshimura K, Trapnell B, Yoneyama K, Rosenthal E, Dalemans W, Fukayama M, Bargon J, Stier L, Stratford-Perricaudet LD, Perrieaudet M, Guggino W, Pavirani A, Lecocq J-P, Crystal RG (1992): In vivo transfer of the human cystic fibrosis transmembrane conductance regulator gene to the airway epithelium. Cell 68: 143–155PubMedCrossRefGoogle Scholar
  43. Rowe WP, Huebner RJ, Gilmore LK, Parrott RH, Ward TG (1953): Isolation of a cytopathogenic agent from human adenoids undergoing spontaneous degeneration in tissue culture. Proc Soc Exp Biol Med 84: 570–573PubMedGoogle Scholar
  44. Severinsson L, Martens I, Peterson PA (1986): Differential association between two human MHC class I antigens and an adenoviral glycoprotein. J Immunol 137: 1003–1009PubMedGoogle Scholar
  45. Stratford-Perricaudet LD, Levrero M, Chasse J-F, Perrieaudet M, Briand P (1990): Evaluation of the transfer and expression in mice of an enzyme-encoding gene using a human adenovirus vector. Hum Gene Ther 1: 241–256PubMedCrossRefGoogle Scholar
  46. Stratford-Perricaudet LD, Perrieaudet M (1991): Gene transfer into animals: The promise of adenovirus. In Human Gene Transfer Vol. 219, Cohen-Haguenauer O, Boiron M, eds. Grenoble, France: John Libbey EurotextGoogle Scholar
  47. Stratford-Perricaudet LD, Briand P, Perrieaudet M (1992b): Feasibility of adenovirus-mediated gene transfer in vivo. Bone Marrow Transplan 9, SI, 151–152Google Scholar
  48. Stratford-Perricaudet LD, Makeh I, Perrieaudet M, Briand P (1992a): Widespread long-term gene transfer to mouse skeletal muscles and heart. J Clin Invest 90: 626–630PubMedCrossRefGoogle Scholar
  49. Straus SE (1984): Adenovirus infections in humans. In The Adenoviruses, Ginsberg HS, ed. New York and London: Plenum PressGoogle Scholar
  50. Top Jr FH, Grossman RA, Bartelloni PJ, Segal HE, Dudding BA, Russell PK, Buescher EL (1971a): Immunization with live types 7 and 4 adenovirus vaccines. I: Safety, infectivity, antigenicity, and potency of adenovirus type 7 vaccines in humans. J Infect Dis 124: 148–155PubMedCrossRefGoogle Scholar
  51. Top Jr FH, Buescher EL, Bencroft WH, Russell PK (1971b): Immunization with live types 7 and 4 adenovirus vaccines. II: Antibody response and protective effect against acute respiratory disease due to adenovirus type 7. J Infect Dis 124: 155–160PubMedCrossRefGoogle Scholar
  52. Williams JF (1986): Adenovirus genetics. In Adenovirus DNA: The Viral Genome and its Expression, Doerfler W, ed. La Hague: Martinus NijhoffGoogle Scholar
  53. Wold WSM, Gooding LR (1989): Adenovirus region E3 proteins that prevent cytolysis by cytotoxic T cells and tumor necrosis factor. Mol Biol Med 6: 433–452PubMedGoogle Scholar
  54. Wold WSM, Gooding LR (1991): Region E3 of adenovirus: A cassette of genes involved in host immunosurveillanee and virus-cell interactions. Virology 184: 1–8PubMedCrossRefGoogle Scholar
  55. Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Feigner PL (1990): Direct gene transfer into mouse muscle in vivo. Science 247: 1456–1468CrossRefGoogle Scholar

Copyright information

© Birkhäuser Boston 1994

Authors and Affiliations

  • Leslie D. Stratford-Perricaudet
  • Michel Perricaudet

There are no affiliations available

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