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BRIEF RESEARCH REPORT article

Front. Mol. Med
Sec. Molecular Mechanisms of Immune Response
Volume 4 - 2024 | doi: 10.3389/fmmed.2024.1492370

An Artificial Transcription Factor that Activates Potent Interferon-γ Expression in Human Jurkat T Cells

Provisionally accepted
Ashley King Ashley King Olivia Sherron Olivia Sherron Lydia Pless Lydia Pless Nicholas Truex Nicholas Truex *
  • University of South Carolina, Columbia, United States

The final, formatted version of the article will be published soon.

    Interferon (IFN)-g is a central regulator of cell-mediated immunity in human health and disease, but reduced expression of the target receptors impairs activity and leads to immunotherapy resistance. This paper presents the design and characterization of an artificial transcription factor (ATF) protein that targets the IFNG gene, instead of cell surface receptors, as a tool to activate endogenous IFN-g expression and direct immune function. The ATF mediates gene recognition with six zinc finger domains, which are dovetailed to a VP64 signaling domain that promotes gene transcription and translation. Biological studies of the ATF revealed increased IFN-g expression by 14-fold in human Jurkat T cells. Biophysical characterization of the ATF showed recognition of the human IFNG gene with nanomolar affinity (KD = 5.27 ± 0.3 nM), protein secondary structure associated with the ββα-fold of zinc finger domains, and resistance to thermal denaturation. These studies demonstrate that transcriptional targeting of cytokine genes, rather than surface receptors, activates cytokine expression and shows significant potential for directing immune function.

    Keywords: transcription factor, Interferon-gamma, enzyme - linked immunosorbent assay (ELISA), Jurkat, Immunotherapy, protein design and engineering

    Received: 06 Sep 2024; Accepted: 28 Nov 2024.

    Copyright: © 2024 King, Sherron, Pless and Truex. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Nicholas Truex, University of South Carolina, Columbia, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.