Gene transfer technology

  • Karen F. Kozarsky
Part of the Progress in Inflammation Research book series (PIR)


In vivo gene transfer is a useful tool for generating animal models of disease, and for validating pathways that are involved in disease. The understanding that is gained through this technology can provide the information needed to develop new therapeutics specifically targeted at the pathways of interest. The choice of gene transfer vector will depend on the tissue and cell types to be transduced, the levels of gene expression needed, and the duration of gene expression. Recent advances in generating recombinant viral vectors, and the identification of new serotypes with different tropism, allow for the generation of a wide range of animal models.


Gene Transfer Recombinant Adenovirus Gene Transfer Vector Gene Transfer Technology Somatic Gene Transfer 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Verma IM, Weitzman MD (2005) Gene therapy: Twenty-first century medicine. Ann Rev Biochem 74: 711–738PubMedCrossRefGoogle Scholar
  2. 2.
    Caplen NJ (2004) Gene therapy progress and prospects. Downregulating gene expression: the impact of RNA interference. Gene Ther 11: 1241–1248PubMedCrossRefGoogle Scholar
  3. 3.
    Bagheri S, Kashani-Sabet M (2004) Ribozymes in the age of molecular therapeutics. Curr Mol Med 4: 489–506PubMedCrossRefGoogle Scholar
  4. 4.
    Herweijer H, Wolff JA (2003) Progress and prospects: naked DNA gene transfer and therapy. Gene Ther 10: 453–458PubMedCrossRefGoogle Scholar
  5. 5.
    Chen ZY, He CY, Meuse L, Kay MA (2004) Silencing of episomal transgene expression by plasmid bacterial DNA elements in vivo. Gene Ther 11: 856–864PubMedCrossRefGoogle Scholar
  6. 6.
    Chen ZY, He CY, Ehrhardt A, Kay MA (2003) Minicircle DNA vectors devoid of bacterial DNA result in persistent and high-level transgene expression in vivo. Mol Ther 8:495–500PubMedCrossRefGoogle Scholar
  7. 7.
    Riu E, Grimm D, Huang Z, Kay MA (2005) Increased maintenance and persistence of transgenes by excision of expression cassettes from plasmid sequences in vivo. Hum Gene Ther 16: 558–570PubMedCrossRefGoogle Scholar
  8. 8.
    Madry H, Cucchiarini M, Stein U, Remberger K, Kohn D, Trippel SB (2003) Sustained transgene expression in cartilage defects in vivo after transplantation of articular chondrocytes modified by lipid-mediated gene transfer in a gel suspension delivery system. J Gene Med 5: 502–509PubMedCrossRefGoogle Scholar
  9. 9.
    Madry H, Kaul G, Cucchiarini M, Stein U, Zurakowski D, Remberger K, Menger MD, Kohn D, Trippel SB (2005) Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulin-like growth factor I (IGF-I). Gene Ther 12: 1171–1179PubMedCrossRefGoogle Scholar
  10. 10.
    Kobinger GP, Deng SP, Louboutin JP, Vatamaniuk M, Matschinsky F, Markmann JF, Raper SE, Wilson JM (2004) Transduction of human islets with pseudotyped lentiviral vectors. Hum Gene Ther 15: 211–219PubMedCrossRefGoogle Scholar
  11. 11.
    Kobinger GP, Weiner DJ, Yu QC, Wilson JM (2001) Filovirus-pseudotyped lentiviral vector can efficiently and stably transduce airway epithelia in vivo. Nat Biotechnol 19:225–230PubMedCrossRefGoogle Scholar
  12. 12.
    Medina MF, Kobinger GP, Rux J, Gasmi M, Looney DJ, Bates P, Wilson JM (2003) Lentiviral vectors pseudotyped with minimal filovirus envelopes increased gene transfer in murine lung. Mol Ther 8: 777–789PubMedCrossRefGoogle Scholar
  13. 13.
    Sinn PL, Sauter SL, McCray PL (2005) Gene therapy progress and prospects: development of improved lentiviral and retroviral vectors-design, biosafety, and production. Gene Ther 12: 1089–1098PubMedCrossRefGoogle Scholar
  14. 14.
    Otani K, Nita I, Macaulay W, Georgescu HI, Robbins PD, Evans CH (1996) Suppression of antigen-induced arthritis in rabbits by ex vivo gene therapy. J Immunol 156:3558–3562PubMedGoogle Scholar
  15. 15.
    Makarov SS, Olsen JC, Johnston WN, Anderle SK, Brown RR, Baldwin AS, Haskill JS, Schwab JH (1996) Suppression of experimental arthritis by gene transfer of interleukin 1 receptor antagonist CDNA. Proc Natl Acad Sci USA 93: 402–406PubMedCrossRefGoogle Scholar
  16. 16.
    Bakker AC, Joosten LAB, Arntz OJ, Helsen MMA, Bendele AM, Vandeloo FAJ, Vandenberg WB (1997) Prevention of murine collagen-induced arthritis in the knee and ipsilateral paw by local expression of human interleukin-1 receptor antagonist protein in the knee. Arthritis Rheum 40: 893–900PubMedGoogle Scholar
  17. 17.
    Pelletier JP, Caron JP, Evans C, Robbins PD, Georgescu HI, Jovanovic D, Fernandes JC, Martelpelletier J (1997) In vivo suppression of early experimental osteoarthritis by interleukin-1 receptor antagonist using gene therapy. Arthritis Rheum 40: 1012–1019PubMedGoogle Scholar
  18. 18.
    Mullerladner U, Roberts CR, Franklin BN, Gay RE, Robbins PD, Evans CH, Gay S (1997) Human IL-1RA gene transfer into human synovial fibroblasts is chondroprotective. J Immunol 158: 3492–3498Google Scholar
  19. 19.
    Kashyap VS, Santamarinafojo S, Brown DR, Parrott CL, Applebaumbowden D, Meyn S, Talley G, Paigen B, Maeda N, Brewer HB (1995) Apolipoprotein E deficiency in mice — gene replacement and prevention of atherosclerosis using adenovirus vectors. J Clin Invest 96: 1612–1620PubMedCrossRefGoogle Scholar
  20. 20.
    Kozarsky KF, Jooss K, Donahee M, Strauss JF, Wilson JM (1996) Effective treatment of familial hypercholesterolemia in the mouse model using adenovirus-mediated transfer of the VLDL receptor gene. Nat Genet 13: 374CrossRefGoogle Scholar
  21. 21.
    Joosten LA, Smeets RL, Koenders MI, van den Bersselaar LA, Helsen MM, Oppers-Walgreen B, Lubberts E, Iwakura Y, van de Loo FA, van den Berg WB (2004) Interleukin-18 promotes joint inflammation and induces interleukin-1-driven cartilage destruction. Am J Pathol 165, 959–967PubMedGoogle Scholar
  22. 22.
    Hui W, Cawston TE, Richards CD, Rowan AD (2004) A model of inflammatory arthritis highlights a role for oncostatin M in pro-inflammatory cytokine-induced bone destruction via RANK/RANKL. Arthritis Res Ther 7: R57–R64PubMedCrossRefGoogle Scholar
  23. 23.
    Rowan AD, Hui W, Cawston TE, Richards CD (2003) Adenoviral gene transfer of interleukin-1 in combination with oncostatin M induces significant joint damage in a murine model. Am J Pathol 162: 1975–1984PubMedGoogle Scholar
  24. 24.
    El Bakkouri K, Wullaert A, Haegman M, Heyninck K, Beyaert R (2005) Adenoviral gene transfer of the NF-kappa B inhibitory protein ABIN-1 decreases allergic airway inflammation in a murine asthma model. J Biol Chem 280: 17938–17944PubMedCrossRefGoogle Scholar
  25. 25.
    Behera AK, Kumar M, Lockey RF, Mohapatra SS (2002) Adenovirus-mediated interferon gamma gene therapy for allergic asthma: Involvement of interleukin 12 and STAT4 signaling. Hum Gene Ther 13: 1697–1709PubMedCrossRefGoogle Scholar
  26. 26.
    Stampfli MR, Cwiartka M, Gajewska BU, Alvarez D, Ritz SA, Inman MD, Xing Z, Jordana M (1999) Interleukin-10 gene transfer to the airway regulates allergic mucosal sensitization in mice. Am J Respir Cell Mol Biol 21: 586–596PubMedGoogle Scholar
  27. 27.
    Walter DM, Wong CP, DeKruyff RH, Berry GJ, Levy S, Umetsu DT (2001) IL-18 gene transfer by adenovirus prevents the development of and reverses established allergen-induced airway hyperreactivity. J Immunol 166: 6392–6398PubMedGoogle Scholar
  28. 28.
    Summerford C, Samulski RJ (1998) Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol 72: 1438–1445PubMedGoogle Scholar
  29. 29.
    Summerford C, Bartlett JS, Samulski RJ (1999) Alpha V beta 5 integrin: a co-receptor for adeno-associated virus type 2 infection. Nat Med 5: 78–82PubMedCrossRefGoogle Scholar
  30. 30.
    Qing K, Mah C, Hansen J, Zhou SZ, Dwarki V, Srivastava A (1999) Human fibroblast growth factor receptor 1 is a co-receptor for infection by adeno-associated virus 2. Nat Med 5: 71–77PubMedCrossRefGoogle Scholar
  31. 31.
    Kaludov N, Brown KE, Walters RW, Zabner J, Chiorini JA (2001) Adeno-associated virus serotype 4 (AAV4) and AAV5 both require sialic acid binding for hemagglutination and efficient transduction but differ in sialic acid linkage specificity. J Virol 75:6884–6893PubMedCrossRefGoogle Scholar
  32. 32.
    Nakai H, Wu XL, Fuess S, Storm TA, Munroe D, Montini E, Burgess SM, Grompe M, Kay MA (2005) Large-scale molecular characterization of adeno-associated virus vector integration in mouse liver. J Virol 79: 3606–3614PubMedCrossRefGoogle Scholar
  33. 33.
    Choi VW, McCarty DM, Samulski RJ (2005) AAV hybrid serotypes: Improved vectors for gene delivery. Curr Gene Ther 5: 299–310PubMedCrossRefGoogle Scholar
  34. 34.
    Gao GP, Vandenberghe LH, Wilson JM (2005) New recombinant serotypes of AAV vectors. Curr Gene Ther 5: 285–297PubMedCrossRefGoogle Scholar
  35. 35.
    Monahan PE, Samulski RJ (2000) Adeno-associated virus vectors for gene therapy: more pros than cons? Mol Med Today 6: 433–440PubMedCrossRefGoogle Scholar
  36. 36.
    Watanabe S, Imagawa T, Boivin GP, Gao GP, Wilson JM, Hirsch R (2000) Adeno-associated virus mediates long-term gene transfer and delivery of chondroprotective IL-4 to murine synovium. Mol Ther 2: 147PubMedCrossRefGoogle Scholar
  37. 37.
    Takahashi H, Kato K, Miyake K, Hirai Y, Yoshino S, Shimada I (2005) Adeno-associated virus vector-mediated anti-angiogenic gene therapy for collagen-induced arthritis in mice. Clin Exp Rheumatol 23: 455–461PubMedGoogle Scholar
  38. 38.
    Zavorotinskaya T, Tomkinson A, Murphy JE (2003) Treatment of experimental asthma by long-term gene therapy directed against IL-4 and IL-13. Mol Ther 7: 155–162PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2006

Authors and Affiliations

  • Karen F. Kozarsky
    • 1
  1. 1.Biopharmaceuticals CEDDGlaxoSmithKlineKing of PrussiaUSA

Personalised recommendations