Promoter Attenuation in Gene Therapy: Interferon-γ and Tumor Necrosis Factor-α Inhibit Transgene Expression
作者： Lihui Qin , Yaozhong Ding , Dominique R. Pahud , Eugenia Chang , Michael J. Imperiale
DOI: 10.1089/HUM.1997.8.17-2019
关键词: Interferon 、 Expression vector 、 Transgene 、 Transfection 、 Molecular biology 、 Biology 、 Rous sarcoma virus 、 Vectors in gene therapy 、 Gene expression 、 Genetic enhancement
摘要: ABSTRACT One of the major limitations to current gene therapy is low-level and transient vector expression due poorly defined mechanisms, possibly including promoter attenuation or extinction. Because application vectors in vivo induces cytokine production through specific nonspecific immune responses, we hypothesized that cytokine-mediated signals may alter expression. Our data indicate cytokines interferon-γ (IFN-γ) tumor necrosis factor-α (TNF-α) inhibit transgene from certain widely used viral promoters/enhancers (cytomegalovirus, Rous sarcoma virus, simian virus 40, Moloney murine leukemia long terminal repeat) delivered by adenoviral, retroviral plasmid vitro. A constitutive cellular (β-actin) less sensitive these effects. Inhibition at mRNA level do not cause DNA degradation, total protein synthesis, kill infected/transfected cells. Admin...
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