Evidence map›Paper›PMID 31672284›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020

Computational Analysis Concerning the Impact of DNA Accessibility on CRISPR-Cas9 Cleavage Efficiency.

Cheng-Han Chung, Alexander G Allen, Neil T Sullivan, Andrew Atkins, Michael R Nonnemacher, Brian Wigdahl, Will Dampier

Abstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing 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

29 citing papers in PubMed.

  1. Efficient Endogenous Tagging in the Sea Urchin,bioRxiv : the preprint server for biology · 2026
    Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Targeted sequencing ofmSystems · 2025
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. An optimized SpCas9 high-fidelity variant for direct protein delivery.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  18. Article
  19. Article
  20. 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

7 authors.

Cheng-Han ChungDepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Alexander G AllenDepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Neil T SullivanDepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Andrew AtkinsDepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Michael R NonnemacherDepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Brian WigdahlDepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. Electronic address: bw45@drexel.edu.
Will DampierDepartment of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA 19129, USA; School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA 19104, USA. Electronic address: wnd22@drexel.edu.

Funding

Viral Gene Editing and Bioinformatics Core for Institution # 269291P30MH092177 · NIMH · TEMPLE UNIV OF THE COMMONWEALTH · PI Ilker Kudret Sariyer · 2011 to 2026
$24.9M
Gene editing strategies to target HIV for elimination in periphery and brainR01MH110360 · NIMH · DREXEL UNIVERSITY · PI Ilker Kudret Sariyer, Brian Wigdahl · 2016 to 2026
$7.3M
Interdisciplinary And Translational Research Training In NeurohivT32MH079785 · NIMH · TEMPLE UNIV OF THE COMMONWEALTH · PI Kamel Khalili · 2008 to 2026
$5.4M
NIMH NIH HHS P30 MH092177NIMH NIH HHS R01 MH110360NIMH NIH HHS T32 MH079785
6 · The paper itself

Abstract

Defining the variables that impact the specificity of CRISPR/Cas9 has been a major research focus. Whereas sequence complementarity between guide RNA and target DNA substantially dictates cleavage efficiency, DNA accessibility of the targeted loci has also been hypothesized to be an important factor. In this study, functional data from two genome-wide assays, genome-wide, unbiased identification of DSBs enabled by sequencing (GUIDE-seq) and circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq), have been computationally analyzed in conjunction with DNA accessibility determined via DNase I-hypersensitive sequencing from the Encyclopedia of DNA Elements (ENCODE) Database and transcriptome from the Sequence Read Archive to determine whether cellular factors influence CRISPR-induced cleavage efficiency. CIRCLE-seq and GUIDE-seq datasets were selected to represent the absence and presence of cellular factors, respectively. Data analysis revealed that correlations between sequence similarity and CRISPR-induced cleavage frequency were altered by the presence of cellular factors that modulated the level of DNA accessibility. The above-mentioned correlation was abolished when cleavage sites were located in less accessible regions. Furthermore, CRISPR-mediated edits were permissive even at regions that were insufficient for most endogenous genes to be expressed. These results provide a strong basis to dissect the contribution of local chromatin modulation markers on CRISPR-induced cleavage efficiency.

Indexed as

Base SequenceCell Line, TumorChromatinClustered Regularly Interspaced Short Palindromic RepeatsComputational BiologyCRISPR-Associated Protein 9CRISPR-Cas SystemsDatabases, GeneticDeoxyribonuclease IDNAGene EditingGenome, HumanHEK293 CellsHigh-Throughput Nucleotide SequencingHumansRNA, Guide, CRISPR-Cas SystemsChromatinCRISPR-Associated Protein 9Deoxyribonuclease IDNARNA, Guide, CRISPR-Cas SystemsbioinformaticschromatinCIRCLE-seqCRISPRDNase-seqGUIDE-seqRNA-seq

Identifiers

PMID31672284
PMCPMC6953893

What Socratic holds

Textmetadata
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 Socratic graph.