Journal of Biomedical Science

, Volume 3, Issue 6, pp 365–378 | Cite as

Transcriptional silencing of retroviral vectors

  • Anders H. Lund
  • Mogens Duch
  • Finn Skou Pedersen


Although retroviral vector systems have been found to efficiently transduce a variety of cell types in vitro, the use of vectors based on murine leukemia virus in preclinical models of somatic gene therapy has led to the identification of transcriptional silencing in vivo as an important problem. Extinction of long-term vector expression has been observed after implantation of transduced hematopoietic cells as well as fibroblasts, myoblasts and hepatocytes. Here we review the influence of vector structure, integration site and cell type on transcriptional silencing. While down-regulation of proviral transcription is known from a number of cellular and animal models, major insight has been gained from studies in the germ line and embryonal cells of the mouse. Key elements for the transfer and expression of retroviral vectors, such as the viral transcriptional enhancer and the binding site for the tRNA primer for reverse transcription may have a major influence on transcriptional silencing. Alterations of these elements of the vector backbone as well as the use of internal promoter elements from housekeeping genes may contribute to reduce transcriptional silencing. The use of cell culture and animal models in the testing and improvement of vector design is discussed.

Key words

Retroviral vectors Gene therapy Stem cells Transcription Silence Inactivation Integration site Position effects Methylation Primer-binding site 


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Copyright information

© National Science Council 1996

Authors and Affiliations

  • Anders H. Lund
    • 2
  • Mogens Duch
    • 2
  • Finn Skou Pedersen
    • 2
    • 1
  1. 1.Department of Medical Microbiology and ImmunologyUniversity of AarhusDenmark
  2. 2.Department of Molecular and Structural BiologyUniversity of AarhusAarhus CDenmark

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