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Gene Delivery to Airways

  • Christian Schatz
  • Andrea Pavirani
Chapter
  • 71 Downloads
Part of the Respiratory Pharmacology and Pharmacotherapy book series (RPP)

Abstract

Experimental evidence for introducing functional genes into tissues and organs has opened new therapeutic approaches to reverse genetic or acquired pathologies. Gene therapy strategies applied to airway disorders (such as cystic fibrosis (CF), cancer and α1-antitrypsin (α1-AT) deficiency) have recently been implemented. At present the direct delivery of beneficial genes to diseased airway cells is accomplished using either replication defective viral vectors, based on the adenovirus, adeno-associated virus (AAV), retroviras genome, or nonviral synthetic vectors, such as cationic lipids complexing plasmid DNA (for review see [1]). Virus-based vectors efficiently transfer foreign genes to different target airway cells. However, safety considerations and limitations, such as host immune response, may limit their application to certain diseases. On the other hand, synthetic vectors are interesting candidates owing to their putative immunotolerance and low toxicity. However, their gene transfer efficiency needs to be increased. Several clinical protocols involving patients with cystic fibrosis, α1 AT deficiency and lung cancer have been approved and conducted in the USA and in Europe. The vast majority involves CF patients.

Keywords

Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Recombinant Adenovirus Nasal Epithelium Cystic Fibrosis Transmembrane Conductance Regulator Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Curiel DT, Pilewski JM, Albelda SM (1996) Gene therapy approaches for inherited and acquired lung diseases. Am J Respir Cell Mol Biol 14: 1–18.PubMedCrossRefGoogle Scholar
  2. 2.
    Boat TF, Welsh MJ, Beaudet AL (1989) Cystic fibrosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds): The Metabolic Basis of Inherited Disease. McGraw-Hill Inc, New York, pp 2649–2680.Google Scholar
  3. 3.
    O’Neal WK, Beaudet AL (1994) Somatic gene therapy for cystic fibrosis. Hum Molec Genet 3: 1497–1502.PubMedGoogle Scholar
  4. 4.
    Crystal RG (1995) Transfer of genes to humans: early lessons and obstacles to success. Science 270: 404–410.PubMedCrossRefGoogle Scholar
  5. 5.
    Crystal RG, McElvaney NG, Rosenfeld MA, Chu C-S, Mastrangeli A, Hay JG, Brody SL, Jaffe AH, Eissa NT, Danel C (1994) Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis. Nature Genet 8: 42–51.PubMedCrossRefGoogle Scholar
  6. 6.
    Zabner J, Couture LA, Gregory RJ, Graham SM, Smith AE, Welsh MJ (1993) Adenovirusmediated gene transfer transiently corrects the chloride transport defect in nasal epithelia of patients with cystic fibrosis. Cell 75: 207–216.PubMedCrossRefGoogle Scholar
  7. 7.
    Caplen NJ, Alton EWFW, Middleton PG, Dorin JR, Stevenson BJ, Gao X, Durham SR, Jeffrey PK, Hodson ME, Coutelle C, et al. (1995) Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Nature Med 1: 39–46.PubMedCrossRefGoogle Scholar
  8. 8.
    Knowles MR, Hohneker K, Zhou Z, Olsen JC, Noah TL, Hu PC, Leigh MW, Engelhardt JF, Edwards LJ, Jones KR, et al. (1995) A controlled study of adenoviral-vector-mediated gene transfer in the nasal epithelium of patients with cystic fibrosis. N Engl J Med 333: 823–831.PubMedCrossRefGoogle Scholar
  9. 9.
    Hay JG, McElvaney NG, Herena J, Crystal RG (1995) Modification of nasal epithelial potential differences of individuals with cystic fibrosis consequent to local administration of a normal CFTR cDNA adenovirus gene tranfer vector. Hum Gene Ther 6: 1487–1496.PubMedCrossRefGoogle Scholar
  10. 10.
    Zabner J, Ramsey BW, Meeker DP, Aitken ML, Balfour RP, Gibson RL, Launspach, Moscicki RA, Richards SM, Standaert TA, et al. (1996) Repeat administration of an adenovirus vector encoding cystic fibrosis transmembrane conductance regulator to the nasal epithelium of patients with cystic fibrosis. J Clin Invest 97: 1504–1511.PubMedCrossRefGoogle Scholar
  11. 11.
    McElvaney NG, Crystal RG (1995) IL-6 release and airway administration of human CFTR cDNA adenovirus vector. Nature Med 1: 182–184.PubMedGoogle Scholar
  12. 12.
    Bellon G, Michel-Calmard L, Thouvenot D, Jagneaux V, Poitevin F, Malcus C, Accart N, Layani M-P, Aymard M, Bernon H, et al. Aerosol administration of a recombinant adenovirus expressing CFTR to cystic fibrosis patients: a phase I clinical trial. Hum Gene Ther 8: 15–25.Google Scholar
  13. 13.
    Roth JA, Nguyen D, Lawrence DD, Kemp BL, Carrasco CH, Ferson DZ et al. (1996) Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer. Nature Med 2:985–991.PubMedCrossRefGoogle Scholar
  14. 14.
    Roth JA (1996) Modification of tumor suppressor gene expression and induction of apoptosis in non-small cell lung cancer (NSCLC) with an adenovirus vector expressing wildtype p53 and cisplatin. Hum Gene Ther 7: 1013–1030.PubMedCrossRefGoogle Scholar
  15. 15.
    Tursz T, Le Cesne A, Baldeyrou P, Gautier E, Opolon P, Schatz C, Pavirani A, Courtney M, Lamy D, Ragot T, et al. Recombinant adenoviral-mediated gene transfer: preliminary report of a phase I study in lung cancer patients. J Natl Cancer Inst 88: 1857–1863.Google Scholar

Copyright information

© Springer Basel AG 1998

Authors and Affiliations

  • Christian Schatz
    • 1
  • Andrea Pavirani
    • 1
  1. 1.Transgène S.A.StrasbourgFrance

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