Coexpression of a Multidrug-resistance Gene(MDR1) and Herpes Simplex Virus Thymidine Kinase Gene as Part of a Bicistronic Messenger RNA in a Retrovirus Vector Allows Selective Killing of MDR1-transduced Cells

Yoshikazu Sugimoto, Ivan Aksentijevich, Michael M. Gottesman

研究成果: Article

32 引用 (Scopus)

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A new retroviral vector, pSXLC/pHa, was constructed to coexpress drug-selectable markers with a second gene of interest as a part of a bicistronic mRNA in a retroviral vector using an internal ribosome entry site (IRES) from encephalomyocarditis virus. This System was used to develop a new retroviral vector pHa-MDR-IRES-TK which expresses a single mRNA from which translation of the MDRl gene is cap dependent and translation of the herpes simplex virus thymidine kinase gene is IRES dependent The pHa-MDR-IRES-TK transfectants showed high levels of P-glycoprotein expression and multidrug resistance. More than 95% of the vincristine-resistant cells transfected or transduced with pHa-MDR-IRES-TK showed hypersensitivity to ganciclovir, which selects against cells expressing herpes simplex virus thymidine kinase. An amphotropic retrovirus titer of 7.8 x 104/ml was obtained with this vector. This safety-modified vector should be useful for introducing the MDRl gene into bone marrow cells to protect normal cells from the toxic effects of cancer chemotherapy because this vector allows the elimination of cancer cells that have been unintentionally transduced with the MDRl vector.

元の言語English
ページ(範囲)447-457
ページ数11
ジャーナルClinical Cancer Research
1
発行部数4
出版物ステータスPublished - 1995 4 1
外部発表Yes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

フィンガープリント Coexpression of a Multidrug-resistance Gene(MDR1) and Herpes Simplex Virus Thymidine Kinase Gene as Part of a Bicistronic Messenger RNA in a Retrovirus Vector Allows Selective Killing of MDR1-transduced Cells' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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