Evidence map›Paper›PMID 39588774›Full record

ArticleNucleic acids research2024

Interpreting CRISPR-Cas12a enzyme kinetics through free energy change of nucleic acids.

Jiongyu Zhang, Xin Guan, Jeong Moon, Shuo Zhang, Zhengyang Jia, Rui Yang, Chengyu Hou, Chong Guo, Minjie Pei, Changchun Liu

Abstract read
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Molecular mechanisms and biotechnology applications of CRISPR-Cas12a.Nature reviews. Molecular cell biology · 2026
    Review
  2. Machine Learning for CRISPR-Based Diagnostics.International journal of molecular sciences · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Facilitating crRNA Design by Integrating DNA Interaction Features of CRISPR-Cas12a System.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  8. Improving plant breeding through AI-supported data integration.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2025
    Review
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

10 authors.

Jiongyu ZhangDepartment of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA.
Xin GuanDepartment of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA.
Jeong MoonDepartment of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA.
Shuo ZhangDepartment of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA.
Zhengyang JiaDepartment of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA.
Rui YangDepartment of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA.
Chengyu HouDepartment of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA.
Chong GuoDepartment of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA.
Minjie PeiDepartment of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA.
Changchun LiuDepartment of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA.ORCID 0000-0002-4931-986X

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 CA269147NIH HHS R33AI154642
6 · The paper itself

Abstract

While CRISPR has revolutionized biotechnology, predicting CRISPR-Cas nuclease activity remains a challenge. Herein, through the trans-cleavage feature of CRISPR-Cas12a, we investigate the correlation between CRISPR enzyme kinetics and the free energy change of crRNA and DNA targets from their initial thermodynamic states to a presumed transition state before hybridization. By subjecting computationally designed CRISPR RNAs (crRNAs), we unravel a linear correlation between the trans-cleavage kinetics of Cas12a and the energy barrier for crRNA spacer and single-stranded DNA target unwinding. This correlation shifts to a parabolic relationship with the energy consumption required for double-stranded DNA target separation. We further validate these correlations using ∼100 randomly selected crRNA/DNA pairs from viral genomes. Through machine learning methods, we reveal the synergistic effect of free energy change of crRNA and DNA on categorizing Cas12a activity on a two-dimensional map. Furthermore, by examining other potential factors, we find that the free energy change is the predominant factor governing Cas12a kinetics. This study will not only empower sequence design for numerous applications of CRISPR-Cas12a systems, but can also extend to activity prediction for a variety of enzymatic reactions driven by nucleic acid dynamics.

Indexed as

CRISPR-Associated ProteinsCRISPR-Cas SystemsThermodynamicsBacterial ProteinsDNADNA, Single-StrandedEndodeoxyribonucleasesKineticsMachine LearningBacterial ProteinsCas12a proteinCRISPR-Associated ProteinsDNADNA, Single-StrandedEndodeoxyribonucleases

Identifiers

PMID39588774
PMCPMC11662684

What OpenQuestion holds

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LicenceCC BY-NC
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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.