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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1469319
This article is part of the Research Topic Signaling Transduction of Innate Immunity and Regulation Mechanisms in the Tumor Immune Microenvironment View all articles

CRISPR-based molecule-regulatory expression platform for specific immunotherapy of cancer

Provisionally accepted
Tianying Zhan Tianying Zhan *Lu Tong Lu Tong Jun Dong Jun Dong Linlin Wang Linlin Wang
  • The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

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

    Cancer is still a major challenge of human health. The abnormality of intracellular cancer-related signal pathways is an important mechanism for the occurrence of cancer. We used a molecular-senor to act on the endogenous signal molecules within the cell to redirect the abnormal signal flows in the cell to treat cancer. Based on CRISPR-dCas12f procedures, we combined aptamers and ribozymes to construct riboswitches, which served as molecular switches to reprogram sgRNAs, so that CRISPR-dCas12f redirected the intracellular anti-cancer signal flows after sensing specific input signal molecules. In addition, the activated molecular sensors and the inhibitory molecular sensors were constructed by combining transcription factors (VP64) and transcription inhibitors (KRAB) to specifically activate and inhibit target genes of interest. Our experimental results showed that the molecular sensors that we designed and constructed specifically sensed the endogenous signal molecules and then redirect the cancer related signal networks of cancer cells. In addition, corresponding logic gates were constructed to distinguish cancer cells from normal cells and redirect anti-cancer signal flows to trigger specific cancer immunotherapy. In conclusion, the constructed molecular sensors constructed specifically recognized the signal molecules within the cell and redirected the endogenous signal pathway to reprogram the fate of cancer cells.

    Keywords: cancer immunotherapy, Bladder cancer, miRNA, Gene circuit, Synthetic Biology

    Received: 23 Jul 2024; Accepted: 08 Oct 2024.

    Copyright: © 2024 Zhan, Tong, Dong and Wang. 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: Tianying Zhan, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

    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.