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Updated: Jul 20, 2026

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
Published on: May 30, 2025
Ribozyme-mediated selective killing of cancer cells expressing carcinoembryonic antigen RNA by targeted
Heung-Su Jung1, Seong-Wook Lee
1Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Seoul 140-714, Republic of Korea.
Abstract:
Carcinoembryonic antigen (CEA) has been shown to be involved in a variety of neoplasia process, such as tumor cell adhesion, metastasis, blocking of cellular immune mechanisms, and anti-apoptosis function. Therefore, CEA has been a potential target for anti-cancer therapy. In this study, we developed a specific ribozyme that can target CEA RNA and then reprogram the RNA with new transcripts, resulting in triggering of transgene activity selectively in cancer cells that express the RNA. The ribozyme-mediated induction of the transgene expression was caused via a highly accurate and specific RNA replacement through trans-splicing reaction with the targeted residue in the CEA-expressing cells. Simultaneously with the specific RNA replacement, the ribozyme efficiently reduced expression level of the targeted CEA RNA in the cells. Importantly, the ribozyme could selectively deliver activity of suicide gene, herpes simplex virus thymidine kinase gene, into cancer cells expressing the CEA RNA and thereby specifically retarded the survival of these cells with ganciclovir treatment. These suggest that the CEA RNA-targeting trans-splicing ribozyme could be a powerful genetic agent for specific cancer gene therapy.
Insights
Researchers developed a novel ribozyme targeting carcinoembryonic antigen (CEA) RNA. This ribozyme selectively triggers gene therapy in cancer cells, offering a promising approach for targeted cancer treatment.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetic Engineering
Background:
- Carcinoembryonic antigen (CEA) is implicated in tumor progression, including metastasis and immune evasion.
- CEA's role in neoplasia makes it a potential therapeutic target for anti-cancer strategies.
Purpose of the Study:
- To develop a specific ribozyme targeting CEA RNA for selective cancer gene therapy.
- To reprogram RNA in CEA-expressing cells to trigger transgene activity and reduce CEA levels.
Main Methods:
- Development of a trans-splicing ribozyme designed to target CEA RNA.
- Utilizing the ribozyme to induce transgene expression and reduce endogenous CEA RNA levels.
- Delivery of a suicide gene (herpes simplex virus thymidine kinase) into CEA-expressing cancer cells.
Main Results:
- The ribozyme achieved accurate and specific RNA replacement via trans-splicing in CEA-expressing cells.
- Significant reduction in targeted CEA RNA expression was observed.
- Selective delivery of suicide gene activity led to specific retardation of cancer cell survival upon ganciclovir treatment.
Conclusions:
- CEA RNA-targeting trans-splicing ribozymes demonstrate potential as effective genetic agents for cancer gene therapy.
- This approach enables selective gene expression and cancer cell killing in CEA-expressing tumors.
- The developed ribozyme offers a precise method for targeting cancer cells based on CEA RNA expression.
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