Evidence map›Paper›PMID 39073026›Full record

ArticleClinical and translational medicine2024

High-fidelity CRISPR/Cas12a dual-crRNA screening reveals novel synergistic interactions in hepatocellular carcinoma.

Qian Chen, Minhui Pang, Peng Chen, Zihao Zhou, Jun Lei, Boxiao He, Zaiqiao Sun, Chonil Paek, Baowei Jing, Yankang Wu and 3 more

Abstract read
In one paragraph

Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Qian ChenState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University, Wuhan, China.
Minhui PangDepartment of Case Statistics, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, China.
Peng ChenState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University, Wuhan, China.
Zihao ZhouState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University, Wuhan, China.
Jun LeiDepartment of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China.
Boxiao HeState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University, Wuhan, China.
Zaiqiao SunState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University, Wuhan, China.
Chonil PaekState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University, Wuhan, China.
Baowei JingState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University, Wuhan, China.
Yankang WuState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University, Wuhan, China.
Shiqi LiuState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University, Wuhan, China.
Yongshun ChenDepartment of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China.
Lei YinState Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, Department of Biochemistry and Molecular Biology, College of Life Sciences, Wuhan University, Wuhan, China.ORCID 0000-0001-5203-2766

Funding

China Postdoctoral Science Foundation 2021TQ0253China Postdoctoral Science Foundation 2022M712468Fundamental Research Funds for the Central Universities 2042022kf1189National Key R&D Program of China 2022YFA1303500National Key Research and Development Program of China 2022YFA1303500National Natural Science Foundation of China 32101196National Natural Science Foundation of China 32171210National Natural Science Foundation of China 32371271
6 · The paper itself

Abstract

: CRISPR/Cas12a-based combinational screening has shown remarkable potential for identifying genetic interactions. Here, we describe an innovative method for combinational genetic screening with rapid construction of a dual-CRISPR RNA (crRNA) library using gene splicing through overlap extension PCR (SOE PCR) and the adoption of CeCas12a, which we previously identified with strict PAM recognition and low off-targeting to guarantee fidelity and efficiency. The custom-pooled SOE crRNA array (SOCA) library for double-knockout screening could be conveniently constructed in the laboratory for widespread use, and the CeCas12a-mediated high-fidelity screen displayed good performance even under a negative selection screen. By designing a SOCA dual-crRNA library that covered most of the kinase and metabolism-associated gene targets of FDA-approved drugs implicated in hepatocellular carcinoma (HCC) tumourigenesis, novel cross-talk between the two gene sets was negatively selected to inhibit HCC cell growth in vitro and in vivo and was validated using virtual double-knockdown screening based on TCGA databases. Thus, this rapid, efficient and high-fidelity double-knockout screening system is promising for systemically identifying potential genetic interactions between multiple gene sets or combinations of FDA- approved drugs for clinical translational medicine in the future.

Indexed as

Carcinoma, HepatocellularCRISPR-Cas SystemsLiver NeoplasmsAnimalsGenetic TestingHumansCeCas12acombinatorial screening of double knockoutshepatocellular carcinoma

Identifiers

PMID39073026
PMCPMC11283585

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.