Evidence map›Paper›PMID 30975459›Full record

ArticleMolecular cell2019

Introducing a Spectrum of Long-Range Genomic Deletions in Human Embryonic Stem Cells Using Type I CRISPR-Cas.

Adam E Dolan, Zhonggang Hou, Yibei Xiao, Max J Gramelspacher, Jaewon Heo, Sara E Howden, Lydia Freddolino, Ailong Ke, Yan Zhang

Open access · greenAbstract read
In one paragraph

Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed, 1 pooled it
8.2field-weighted citation impact, top 2% 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

100 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Sensitizing carbapenem-resistant Klebsiella pneumoniae using a compact Cascade-Cas3 system.International microbiology : the official journal of the Spanish Society for Microbiology · 2026
    Article
  4. Article
  5. Article
  6. Gigabase-scale deletion scanning of the human genome.bioRxiv : the preprint server for biology · 2026
    Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. A Manual for Genome and Transcriptome Engineering.IEEE reviews in biomedical engineering · 2025
    Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article

40 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 3 countries.

Adam E DolanDepartment of Molecular Biology and Genetics, Cornell University, 253 Biotechnology Building, Ithaca, NY 14853, USA.
Zhonggang HouDepartment of Biological Chemistry, University of Michigan, 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USA.
Yibei XiaoDepartment of Molecular Biology and Genetics, Cornell University, 253 Biotechnology Building, Ithaca, NY 14853, USA; State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
Max J GramelspacherDepartment of Biological Chemistry, University of Michigan, 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USA.
Jaewon HeoDepartment of Biological Chemistry, University of Michigan, 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USA.
Sara E HowdenMurdoch Children's Research Institute, Flemington Rd., Parkville, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia.
Lydia FreddolinoDepartment of Biological Chemistry, University of Michigan, 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA.
Ailong KeDepartment of Molecular Biology and Genetics, Cornell University, 253 Biotechnology Building, Ithaca, NY 14853, USA. Electronic address: ailong.ke@cornell.edu.
Yan ZhangDepartment of Biological Chemistry, University of Michigan, 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USA. Electronic address: yzhangbc@med.umich.edu.
University of Michigan–Ann Arbor · USCornell University · USChina Pharmaceutical University · CNUniversity of Melbourne · AU

Funding

Mechanistic Investigation of RNA-Mediated Gene Regulation and ImmunityR35GM118174 · NIGMS · YALE UNIVERSITY · PI AILONG KE · 2016 to 2026
$7.9M
Building a unified framework for understanding bacterial gene regulation and chromosomal architectureR35GM128637 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Lydia Petra Freddolino · 2018 to 2026
$3.6M
Structure and mechanism of CRISPR interference.R01GM102543 · NIGMS · CORNELL UNIVERSITY · PI KE, AILONG · 2013 to 2015
$917k
The alternative roles of Neisseria CRISPR-Cas9 in endogenous gene regulation and bacterial physiologyR00GM117268 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZHANG, YAN · 2017 to 2019
$747k
The alternative roles of Neisseria CRISPR-Cas9 in endogenous gene regulation and bacterial physiologyK99GM117268 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ZHANG, YAN · 2016 to 2017
$104k
NIGMS NIH HHS K99 GM117268NIGMS NIH HHS R00 GM117268NIGMS NIH HHS R01 GM102543NIGMS NIH HHS R35 GM118174NIGMS NIH HHS R35 GM128637
6 · The paper itself

Abstract

CRISPR-Cas systems enable microbial adaptive immunity and provide eukaryotic genome editing tools. These tools employ a single effector enzyme of type II or V CRISPR to generate RNA-guided, precise genome breaks. Here we demonstrate the feasibility of using type I CRISPR-Cas to effectively introduce a spectrum of long-range chromosomal deletions with a single RNA guide in human embryonic stem cells and HAP1 cells. Type I CRISPR systems rely on the multi-subunit ribonucleoprotein (RNP) complex Cascade to identify DNA targets and on the helicase-nuclease enzyme Cas3 to degrade DNA processively. With RNP delivery of T. fusca Cascade and Cas3, we obtained 13%-60% editing efficiency. Long-range PCR-based and high-throughput-sequencing-based lesion analyses reveal that a variety of deletions, ranging from a few hundred base pairs to 100 kilobases, are created upstream of the target site. These results highlight the potential utility of type I CRISPR-Cas for long-range genome manipulations and deletion screens in eukaryotes.

Indexed as

Human Embryonic Stem CellsCRISPR-Cas SystemsEndonucleasesEscherichia coliGene EditingGenome, HumanGenomicsHumansRibonucleoproteinsRNA, Guide, CRISPR-Cas SystemsSequence DeletionEndonucleasesRibonucleoproteinsRNA, Guide, CRISPR-Cas SystemsCas3CascadechromosomeCRISPR-Casembryonic stem cellgenome editinglarge genome deletionlong-rangeRNA-guidedtype I CRISPR

Identifiers

PMID30975459
PMCPMC6555677
OpenAlexW2939691756

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.