Interferon (IFN)-γ is a central regulator of cell-mediated immunity in human health and disease, but reduced expression of the target receptors impairs signaling activity and leads to immunotherapy resistance. Although intracellular expression of IFN-γ restores the signaling and downstream functions, we lack the tools to activate the gene instead of cell surface receptors. This paper introduces the design and characterization of an artificial transcription factor (ATF) protein that recognizes the gene with six zinc finger domains, which are dovetailed to a VP64 signaling domain that promotes gene transcription and translation.
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