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

IntroductionCancer 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.MethodsWe used a molecular-senor to act on the endogenous signal molecules within the cell to redirect the abnormal si...

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Main Authors: Tianying Zhan, Lu Tong, Linlin Wang, Jun Dong
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-10-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2024.1469319/full
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author Tianying Zhan
Lu Tong
Linlin Wang
Jun Dong
author_facet Tianying Zhan
Lu Tong
Linlin Wang
Jun Dong
author_sort Tianying Zhan
collection DOAJ
description IntroductionCancer 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.MethodsWe 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.ResultsOur 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 anticancer signal flows to trigger specific cancer immunotherapy.ConclusionThe 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.
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spelling doaj-art-f89bc70a2e59415daaf33e3dcb24694e2025-08-20T02:09:48ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-10-011410.3389/fonc.2024.14693191469319CRISPR-based molecule-regulatory expression platform for specific immunotherapy of cancerTianying ZhanLu TongLinlin WangJun DongIntroductionCancer 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.MethodsWe 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.ResultsOur 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 anticancer signal flows to trigger specific cancer immunotherapy.ConclusionThe 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.https://www.frontiersin.org/articles/10.3389/fonc.2024.1469319/fullcancer immunotherapybladder cancermiRNAgene circuitsynthetic biology
spellingShingle Tianying Zhan
Lu Tong
Linlin Wang
Jun Dong
CRISPR-based molecule-regulatory expression platform for specific immunotherapy of cancer
Frontiers in Oncology
cancer immunotherapy
bladder cancer
miRNA
gene circuit
synthetic biology
title CRISPR-based molecule-regulatory expression platform for specific immunotherapy of cancer
title_full CRISPR-based molecule-regulatory expression platform for specific immunotherapy of cancer
title_fullStr CRISPR-based molecule-regulatory expression platform for specific immunotherapy of cancer
title_full_unstemmed CRISPR-based molecule-regulatory expression platform for specific immunotherapy of cancer
title_short CRISPR-based molecule-regulatory expression platform for specific immunotherapy of cancer
title_sort crispr based molecule regulatory expression platform for specific immunotherapy of cancer
topic cancer immunotherapy
bladder cancer
miRNA
gene circuit
synthetic biology
url https://www.frontiersin.org/articles/10.3389/fonc.2024.1469319/full
work_keys_str_mv AT tianyingzhan crisprbasedmoleculeregulatoryexpressionplatformforspecificimmunotherapyofcancer
AT lutong crisprbasedmoleculeregulatoryexpressionplatformforspecificimmunotherapyofcancer
AT linlinwang crisprbasedmoleculeregulatoryexpressionplatformforspecificimmunotherapyofcancer
AT jundong crisprbasedmoleculeregulatoryexpressionplatformforspecificimmunotherapyofcancer