Synthesizing AND gate genetic circuits based on CRISPR-Cas9 for identification of bladder cancer cells
Open accessAbstract
The conventional strategy for cancer gene therapy offers limited control of specificity and efficacy. A possible way to overcome these limitations is to construct logic circuits. Here we present modular AND gate circuits based on CRISPR-Cas9 system. The circuits integrate cellular information from two promoters as inputs and activate the output gene only when both inputs are active in the tested cell lines. Using the luciferase reporter as the output gene, we show that the circuit specifically detects bladder cancer cells and significantly enhances luciferase expression in comparison to the human telomerase reverse transcriptase-renilla luciferase construct. We also test the modularity of the design by replacing the output with other cellular functional genes including hBAX, p21 and E-cadherin. The circuits effectively inhibit bladder cancer cell growth, induce apoptosis and decrease cell motility by regulating the corresponding gene. This approach provides a synthetic biology platform for targeting and controlling bladder cancer cells in vitro.
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In bladder cancer cells, Cas9 and sgRNAs were both expressed, mutating the LacI gene and abrogating its suppression on the effector gene, leading to bladder cancer cell-specific expression of the effector.
“In bladder cancer cells, Cas9 and sgRNAs were both expressed, mutating LacI gene and abrogating its suppression on the effector gene, leading to bladder cancer cell-specific expression of the effector (figure 2C, right).”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [47]
Liu et al used CRISPR-Cas9-mediated bladder cancer cell-specific genome editing using an AND logic gate.
“An example of therapeutic genome manipulations comes from study by Liu et al 47 in which CRISPR-Cas9-mediated bladder cancer cell-specific genome editing using an AND logic gate (figure 2).”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [47]
In the Liu et al study, effector genes p21, E-cadherin and Bax led to cancer-specific growth inhibition, migration suppression and apoptosis, respectively.
“In this study, the effector genes were p21, E-cadherin and Bax (BCL2-associated X), leading to cancer-specific growth inhibition, migration suppression and apoptosis, respectively.”
From CRISPR-Cas9: a new and promising player in gene therapy (2015) · cites this paper as [47]
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- Authors
- Liu, Y., Zeng, Y., Liu, L., Zhuang, C., Fu, X., Huang, W., & Cai, Z.
- Affiliations
- Shenzhen University (CN)
- Corresponding author
- Huang, Weiren
- Cai, Zhiming
- Venue
- Nature Communications
- Published
- 2014-11-06
- Volume
- 5
- Issue
- 1
- Pages
- 5393-5393
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W1998857871
- Cited by
- 223
- References
- 34
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 16 · 2023: 8 · 2022: 28 · 2021: 16 · 2020: 21 · 2019: 23 · 2018: 18 · 2017: 27 · 2016: 24 · 2015: 22
- FWCI
- 9.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Natural Science Foundation of China (81100460, 2014CB745201, JCYJ20120614155650545)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Keywords
- CRISPR/Cas9, synthetic gene circuits, bladder cancer, cancer cell detection, luciferase reporter, human telomerase reverse transcriptase, apoptosis, cell motility, gene expression regulation, cancer gene therapy
- MeSH terms
- Urinary Bladder Neoplasms, Cell Movement, Humans, Molecular Sequence Data, Cadherins, Gene Expression Regulation, Neoplastic, Apoptosis, Telomerase, Cell Line, Tumor, Luciferases, Renilla, bcl-2-Associated X Protein, Gene Regulatory Networks, Uroplakin II, CRISPR-Cas Systems
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