Evidence map›Paper›PMID 38516796›Full record

ArticleAngewandte Chemie (International ed. in English)2024

Intrinsic RNA Targeting Triggers Indiscriminate DNase Activity of CRISPR-Cas12a.

Jiongyu Zhang, Ziyue Li, Chong Guo, Xin Guan, Lori Avery, David Banach, Changchun Liu

Open access · bronzeAbstract read
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
14.0field-weighted citation impact, top 1% of its field
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

23 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. AsCas12a tolerates insertions in target DNA.Nucleic acids research · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Expanding Cas12a Activity Control with an RNA G-Quadruplex at the 5' end of CRISPR RNA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. 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

7 authors at 2 institutions in 1 country.

Jiongyu ZhangDepartment of Biomedical Engineering, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut, 06030, United States.
Ziyue LiDepartment of Biomedical Engineering, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut, 06030, United States.
Chong GuoDepartment of Biomedical Engineering, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut, 06030, United States.
Xin GuanDepartment of Biomedical Engineering, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut, 06030, United States.
Lori AveryDepartment of Pathology and Laboratory Medicine, University of Connecticut Health Center, Farmington, Connecticut, 06030, United States.
David BanachDepartment of Medicine, Division of Infectious Diseases, University of Connecticut Health Center, Farmington, Connecticut, 06030, United States.
Changchun LiuDepartment of Biomedical Engineering, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut, 06030, United States.ORCID 0000-0002-4931-986X
University of Connecticut · USUConn Health · US

Funding

Low-Cost CRISPR-on-Paper for Cervical Cancer Screening at the Point of CareU01CA269147 · NCI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI Changchun Liu · 2022 to 2026
$2.6M
Self-Powered Sample Concentrating and CRISPR-based Biosensing for Moile HIV-1 RNA DetectionR33AI154642 · NIAID · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI LIU, CHANGCHUN · 2023 to 2024
$1.6M
NCI NIH HHS U01 CA269147NIAID NIH HHS R33 AI154642
6 · The paper itself

Abstract

The CRISPR-Cas12a system has emerged as a powerful tool for next-generation nucleic acid-based molecular diagnostics. However, it has long been believed to be effective only on DNA targets. Here, we investigate the intrinsic RNA-enabled trans-cleavage activity of AsCas12a and LbCas12a and discover that they can be directly activated by full-size RNA targets, although LbCas12a exhibits weaker trans-cleavage activity than AsCas12a on both single-stranded DNA and RNA substrates. Remarkably, we find that the RNA-activated Cas12a possesses higher specificity in recognizing mutated target sequences compared to DNA activation. Based on these findings, we develop the "Universal Nuclease for Identification of Virus Empowered by RNA-Sensing" (UNIVERSE) assay for nucleic acid testing. We incorporate a T7 transcription step into this assay, thereby eliminating the requirement for a protospacer adjacent motif (PAM) sequence in the target. Additionally, we successfully detect multiple PAM-less targets in HIV clinical samples that are undetectable by the conventional Cas12a assay based on double-stranded DNA activation, demonstrating unrestricted target selection with the UNIVERSE assay. We further validate the clinical utility of the UNIVERSE assay by testing both HIV RNA and HPV 16 DNA in clinical samples. We envision that the intrinsic RNA targeting capability may bring a paradigm shift in Cas12a-based nucleic acid detection and further enhance the understanding of CRISPR-Cas biochemistry.

Indexed as

CRISPR-Associated ProteinsCRISPR-Cas SystemsRNABacterial ProteinsDeoxyribonucleasesEndodeoxyribonucleasesHumansBacterial ProteinsCas12a proteinCRISPR-Associated ProteinsDeoxyribonucleasesEndodeoxyribonucleasesRNACRISPR-Cas12anucleic acid detectionprotospacer adjacent motif (PAM)-freeRNA-activationtrans-cleavage

Identifiers

PMID38516796
PMCPMC11073899
OpenAlexW4393089505

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.