Evidence map›Paper›PMID 39003402›Full record

ArticleCommunications biology2024

Repurposing Type I-A CRISPR-Cas3 for a robust diagnosis of human papillomavirus (HPV).

Tao Hu, Quanquan Ji, Xinxin Ke, Hufeng Zhou, Senfeng Zhang, Shengsheng Ma, Chenlin Yu, Wenjun Ju, Meiling Lu, Yu Lin and 5 more

Abstract read
In one paragraph

Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

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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.

Tao HuChildren's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Zhejiang University, Hangzhou, Zhejiang, 310052, China.
Quanquan JiCancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Xinxin KeChildren's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Zhejiang University, Hangzhou, Zhejiang, 310052, China.
Hufeng ZhouDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0001-9382-5674
Senfeng ZhangDepartment of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, 117543, Singapore.
Shengsheng MaDepartment of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, 117543, Singapore.
Chenlin YuDepartment of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, China.
Wenjun JuDepartment of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, China.
Meiling LuDepartment of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, China.
Yu LinInternational Peace Maternity & Child Health Hospital, Shanghai Municipal Key Clinical Specialty, Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.
Yangjing OuInternational Peace Maternity & Child Health Hospital, Shanghai Municipal Key Clinical Specialty, Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.
Yingsi ZhouHuidaGene Therapeutics Inc., Shanghai, China. yingsizhou@huidagene.com.ORCID 0000-0002-6541-2116
Yibei XiaoDepartment of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, China. yibei.xiao@cpu.edu.cn.ORCID 0000-0003-4716-5526
Chunlong XuLingang Laboratory, Shanghai, China. xucl@lglab.ac.cn.ORCID 0000-0003-3533-3465
Chunyi HuDepartment of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, 117543, Singapore. hu_dbs@nus.edu.sg.ORCID 0000-0003-4509-4840

Funding

National University of Singapore (NUS) 23-0178-A0003
6 · The paper itself

Abstract

R-loop-triggered collateral single-stranded DNA (ssDNA) nuclease activity within Class 1 Type I CRISPR-Cas systems holds immense potential for nucleic acid detection. However, the hyperactive ssDNase activity of Cas3 introduces unwanted noise and false-positive results. In this study, we identified a novel Type I-A Cas3 variant derived from Thermococcus siculi, which remains in an auto-inhibited state until it is triggered by Cascade complex and R-loop formation. This Type I-A CRISPR-Cas3 system not only exhibits an expanded protospacer adjacent motif (PAM) recognition capability but also demonstrates remarkable intolerance towards mismatched sequences. Furthermore, it exhibits dual activation modes-responding to both DNA and RNA targets. The culmination of our research efforts has led to the development of the Hyper-Active-Verification Establishment (HAVE, ). This innovation enables swift and precise human papillomavirus (HPV) diagnosis in clinical samples, providing a robust molecular diagnostic tool based on the Type I-A CRISPR-Cas3 system. Our findings contribute to understanding type I-A CRISPR-Cas3 system regulation and facilitate the creation of advanced diagnostic solutions with broad clinical applicability.

Indexed as

CRISPR-Cas SystemsPapillomavirus InfectionsCRISPR-Associated ProteinsHuman Papillomavirus VirusesHumansPapillomaviridaeCRISPR-Associated Proteins

Identifiers

PMID39003402
PMCPMC11246428

What OpenQuestion holds

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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 OpenQuestion graph.