Synthesizing a Genetic Sensor Based on CRISPR-Cas9 for Specifically Killing p53-Deficient Cancer Cells
Abstract
Cancer is still one of the greatest medical challenges in the world. The p53 protein plays an important role in the process of cancer formation. In addition, p53 is found as the most common mutant gene in cancers. Because of the central role of p53 in oncology, it is necessary to construct effective sensors to detect this protein. However, there are few methods to detect wild type p53 protein (WTP53) or to distinguish the wild type and mutant p53 proteins. In our study, we designed and constructed a p53 genetic sensor that detected the expression of WTP53 in cells. Moreover, we combined the p53 sensor with diphtheria toxin using the CRISPR-Cas9 system to construct a p53 genetic sensor that specifically killed p53-deficient cells such as tumor cells. Our study therefore developed a new way to treat cancers by using an available genetic sensor based on p53 protein.
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The p53 genetic sensor selectively killed p53-deficient tumor cells by becoming activated in the presence of wild-type p53, while protecting normal cells from diphtheria toxin.
“The sensor selectively killed p53-deficient tumor cells by becoming activated in the presence of WT p53, while protecting normal cells from diphtheria toxin.582”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [582]
Huang and Liu's group constructed a p53 genetic sensor and combined it with diphtheria toxin using the CRISPR-Cas9 system to specifically eliminate p53-deficient cells.
“In the meantime, Huang and Liu’s group constructed a p53 genetic sensor compound (247), and combined it with diphtheria toxin using the CRISPR-Cas9 system to specifically eliminate p53-deficient cells.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [582]
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Zhan, T., Li, X., Liu, J., & 叶楚津 (2024) · Figshare · doi:10.6084/m9.figshare.25792712
- Authors
- Zhan, H., Xie, H., Zhou, Q., Liu, Y., & Huang, W.
- Affiliations
- Shenzhen University (CN)
- Corresponding author
- Liu, Yuchen
- Huang, Weiren
- Venue
- ACS Synthetic Biology
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-06-29
- Volume
- 7
- Issue
- 7
- Pages
- 1798-1807
- ISSN
- 2161-5063 (ISSN-L)
- OpenAlex
- W2810238193
- Cited by
- 36
- References
- 35
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 7 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 7 · 2019: 1 · 2018: 2
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Synthetic Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology of the People's Republic of China (2014CB745201)
- National Natural Science Foundation of China (81772737)
- Shenzhen Municipality (JCYJ20170413161749433, JSGG20160301161836370, 2016031638)
- Shenzhen Health and Family Planning Commission (SZSM201412018, SZSM201512037)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- p53, CRISPR/Cas9, diphtheria toxin, targeted cell killing, cancer therapy
- MeSH terms
- Humans, Tumor Suppressor Protein p53, CRISPR-Cas Systems
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