Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Biomedical Science |
| Vol/bind | 3 |
| Udgave nummer | 6 |
| Sider (fra-til) | 365-378 |
| Antal sider | 13 |
| ISSN | 1021-7770 |
| Status | Udgivet - 1996 |
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Transcriptional Silencing of Retroviral Vectors. / Lund, Anders Henrik; Duch, M.; Pedersen, F.S.
I: Journal of Biomedical Science, Bind 3, Nr. 6, 1996, s. 365-378.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Transcriptional Silencing of Retroviral Vectors.
AU - Lund, Anders Henrik
AU - Duch, M.
AU - Pedersen, F.S.
PY - 1996
Y1 - 1996
N2 - 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. Copyright 1996 S. Karger AG, Basel
AB - 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. Copyright 1996 S. Karger AG, Basel
M3 - Journal article
C2 - 11725119
VL - 3
SP - 365
EP - 378
JO - Journal of Biomedical Science
JF - Journal of Biomedical Science
SN - 1021-7770
IS - 6
ER -