Evidence map›Paper›PMID 41404798›Full record

ArticleNucleic acids research2025

Amplification-free cancer diagnosis based on inhibition of Cas12a activity by site-specific 5mC-modified cfDNA.

Feng Yang, Can Xu, Chunhong Li, Xinni Xiang, Yi Zhao, Cong Hu, Huan Rong, Yu He, Jingyu Li, Yu Wang and 5 more

Abstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

15 authors.

Feng YangChongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China.
Can XuInstitute of Image Processing and Pattern Recognition, Shanghai Jiao Tong University, 800 Dongchuan RD, Minhang District, Shanghai 200240, China.
Chunhong LiChongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China.
Xinni XiangChongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China.
Yi ZhaoChongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China.
Cong HuChongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China.
Huan RongChongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China.
Yu HeChongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China.
Jingyu LiDepartment of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Yu WangChongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China.
Chao TangChongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China.
Xiaoyu LiuChongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China.
Renyan LiChongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China.ORCID 0000-0002-8843-5185
Fei DengGraduate School of Biomedical Engineering, Faculty of Engineering, University of New South Wales, Sydney, NSW 2052, Australia.ORCID 0000-0002-5606-0278
Tingxiu XiangChongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital, Chongqing University, Chongqing 400030, China.ORCID 0009-0005-4724-3493

Funding

Chongqing Municipal Science and Health Joint Medical Research 2024MSXM136Enhancing Scientific Research Capabilities of Chongqing University Cancer Hospital 2023nlts007National Natural Science Foundation of China 82172619Outstanding Young Talents Program of Chongqing YXQN202421
6 · The paper itself

Abstract

DNA methylation detection holds significant value for cancer diagnosis and recurrence monitoring. However, current methods are often time-consuming, costly, and necessitate specialized techniques. The CRISPR-Cas system, particularly Cas12a, presents a precise and user-friendly platform for disease diagnosis. We developed the CRISPR-Methylated DNA Detection Test (CRISPR-MeDNA Test), a Cas12a-based method for detecting methylation in plasma cell-free DNA (cfDNA). The results reveal that 5mC-modified DNA significantly suppresses the trans-cleavage activity of Cas12a, depending on the methylation site, number, and interval spacing. Simultaneously, methylation of the non-target strand (NTS) suppresses Cas12a activity more strongly than methylation of the target strand (TS), as the NTS plays a critical role in R-loop formation, which is essential for Cas12a cleavage target DNA. Mechanistically, 5mC-modified DNA was found to trigger conformational rearrangements in the Cas12a complex, as predicted by AlphaFold3 modeling and corroborated by FRET assays. Notably, the combination of Cas12a with multiplexed guide RNAs enables effective discrimination between cfDNA from healthy donors and cancer patients without the need for pre-amplification, based on the inhibitory effects of methylated DNA on the Cas12a trans-cleavage activity. This work provides a Cas12a-based detection for a rapid, cost-effective, low-complexity method for 5mC-modified cfDNA in liquid biopsies.

Indexed as

Cell-Free Nucleic AcidsCRISPR-Associated ProteinsCRISPR-Cas SystemsDNA MethylationEndodeoxyribonucleasesNeoplasmsBacterial ProteinsHumansBacterial ProteinsCas12a proteinCell-Free Nucleic AcidsCRISPR-Associated ProteinsEndodeoxyribonucleases

Identifiers

PMID41404798
PMCPMC12709189

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

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 Socratic graph.