Related Experiment Video
Updated: Jan 15, 2026
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
A First-in-Class Chemical-Induced Proximity System Achieves Dose-Dependent Control of Tumor Protein P53 Gene
Travis J Nelson1,2, Ryan M Kemper3, Anna M Chiarella1,2
1Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, United States.
Abstract:
The tumor protein P53 (TP53) gene has long been studied in cancer research with genomic and epigenetic aberrations playing a driving role in cancer pathology, yet even after decades of work, only a few methods have been developed to specifically target TP53 therapeutically. Some cancers are driven by loss-of-function TP53 mutations, while others have wild-type TP53 in a transcriptionally repressed state; the latter is exploitable by advances in epigenome editing. In our previous work, we demonstrated that deactivated CRISPR/Cas9 systems (dCas9), combined with an FK-506-binding protein (FKBP) recruitment protein tag and chemical epigenetic modifier (CEM) small molecules, can elicit gene-specific changes in expression in a dose-dependent manner. Here, we describe the development, application, and characterization of the dCas9-FKBP-CEM technology to increase TP53 expression. We demonstrate that catalyzing increased TP53 expression via dCas9-FKBP-CEM87 induced apoptosis, cell cycle arrest, and tumor growth inhibition in a dose-dependent manner in preclinical models of gastric cancer.
Insights
Researchers developed a new epigenome editing technology to increase tumor protein P53 (TP53) expression. This approach effectively inhibited gastric cancer growth by inducing apoptosis and cell cycle arrest in preclinical models.
Area of Science:
- Cancer Biology
- Epigenetics
- Gene Therapy
Background:
- The tumor protein P53 (TP53) gene is crucial in cancer pathology, with aberrations driving disease.
- Targeting TP53 therapeutically remains challenging, especially in cancers with wild-type TP53 in a repressed state.
- Epigenome editing offers a novel strategy to modulate TP53 expression in such cancers.
Purpose of the Study:
- To develop and characterize a dCas9-FKBP-CEM technology for targeted TP53 upregulation.
- To investigate the therapeutic potential of this technology in preclinical cancer models.
Main Methods:
- Utilized deactivated CRISPR/Cas9 (dCas9) fused to an FK-506-binding protein (FKBP) tag.
- Employed chemical epigenetic modifier (CEM) small molecules for gene-specific expression changes.
- Applied the dCas9-FKBP-CEM system to increase TP53 expression in gastric cancer models.
Main Results:
- Demonstrated dose-dependent induction of TP53 expression using dCas9-FKBP-CEM87.
- Observed significant induction of apoptosis and cell cycle arrest in cancer cells.
- Showcased inhibition of tumor growth in preclinical gastric cancer models.
Conclusions:
- The dCas9-FKBP-CEM technology is effective in increasing TP53 expression.
- This epigenome editing approach shows therapeutic promise for cancers with repressed TP53.
- The technology induced significant anti-cancer effects, including apoptosis and tumor growth inhibition.
More Related Videos
Related Concept Videos
02:23Abnormal Proliferation
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...