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Description
  • The transcriptional silencing of retroviral vectors represents major complication of efficient gene transfer in gene therapy applications. The extent of silencing differs among retroviral vectors of different origin. ASLV-based vectors are particularly affected in mammalian cells, which prevent their otherwise great potential in gene therapy. Silencing of retroviral vectors is observed in two experimental settings: gradual silencing during long-term cultivation and early silencing during the process of integration into the host genome. We will (1) establish a quantitative assay for the analysis of early silencing, (2) explore the role of certain cellular factors, e.g. Daxx protein, in early silencing and integration preference of ASLV-derived vectors, and (3) assess the role of various types of DNA methyltransferases in vector silencing. We will also (4) test the antisilencing properties of the core sequence of a CpG island that previously turned out to be an efficient protective element against the gradual silencing. Understanding the mechanisms of retroviral silencing will help in the design of new optimized vectors for gene therapy. (en)
  • Určení role proteinu Daxx a savčích methyltransferáz v umlčování retrovirových vektorů na báza ASLV v savčích buňkách. Posouzení možné ochrany těchto vektorů před umlčením vložením vnitřního elementu z CpG ostrova a studium mechanismu této ochrany
Title
  • Transcriptional silencing of retroviral vectors during their integration into the host genome (en)
  • Transkripční umlčování retrovirových vektorů během jejich integrace do hostitelského genomu
skos:notation
  • GP301/09/P667
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  • retrovirus, ASLV, integrace, umlčování, methylace DNA, Daxx, DNA methyltransferáza (en)
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  • The project was excellent, both in terms of expertise and in terms of disbursement of funds. (en)
  • Řešení projektu proběhlo na vynikající úrovni, a to jak z hlediska odborného tak i z hlediska čerpání finančních prostředků. (cs)
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http://linked.open.../cep/klicoveSlovo
  • retrovirus
  • ASLV
  • Daxx
  • integrace
  • methylace DNA
  • umlčování
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