Evidence map›Paper›PMID 26916719›Full record

ArticleNature communications2016

Multiplexed pancreatic genome engineering and cancer induction by transfection-based CRISPR/Cas9 delivery in mice.

Roman Maresch, Sebastian Mueller, Christian Veltkamp, Rupert Öllinger, Mathias Friedrich, Irina Heid, Katja Steiger, Julia Weber, Thomas Engleitner, Maxim Barenboim and 20 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2016. 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
14.6field-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

100 citing papers in PubMed, 1 synthesis or guideline pooled it, 171 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. International journal of biological sciences · 2026
    Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. Harnessing the evolving CRISPR/Cas9 for precision oncology.Journal of translational medicine · 2024
    Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. CRISPRingCancers · 2024
    Review
  18. Review
  19. Review
  20. Review

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

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

30 authors at 7 institutions in 3 countries.

Roman MareschDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Sebastian MuellerDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Christian VeltkampDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Rupert ÖllingerDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Mathias FriedrichWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Irina HeidInstitute of Radiology, Klinikum rechts der Isar, Technischen Universität München, 81675 Munich, Germany.
Katja SteigerDepartment of Pathology, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Julia WeberDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Thomas EngleitnerDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Maxim BarenboimDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Sabine KleinDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Sandra LouzadaWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Ruby BanerjeeWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Alexander StrongWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Teresa StauberDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Nina GrossDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Ulf GeumannDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Sebastian LangeDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Marc RingelhanDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Ignacio VarelaInstituto de Biomedicina y Biotecnología de Cantabria, 39011 Santander, Spain.
Kristian UngerHelmholtz Zentrum München, Research Unit Radiation Cytogenetics, 85764 Neuherberg, Germany.
Fengtang YangWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Roland M SchmidDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
George S VassiliouWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Rickmer BrarenInstitute of Radiology, Klinikum rechts der Isar, Technischen Universität München, 81675 Munich, Germany.
Günter SchneiderDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Mathias HeikenwalderInstitute of Virology, Technische Universität München/Helmholtz Zentrum München, 81675 Munich, Germany.
Allan BradleyWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Dieter SaurDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Roland RadDepartment of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany.
Technical University of Munich · DEWellcome Sanger Institute · GBKlinikum rechts der Isar · DEHeidelberg University · DEGerman Cancer Research Center · DEHelmholtz Zentrum München · DEInstituto de Biomedicina y Biotecnología de Cantabria · ES

Funding

European Research Council 648521Medical Research Council MC_PC_12009
6 · The paper itself

Abstract

Mouse transgenesis has provided fundamental insights into pancreatic cancer, but is limited by the long duration of allele/model generation. Here we show transfection-based multiplexed delivery of CRISPR/Cas9 to the pancreas of adult mice, allowing simultaneous editing of multiple gene sets in individual cells. We use the method to induce pancreatic cancer and exploit CRISPR/Cas9 mutational signatures for phylogenetic tracking of metastatic disease. Our results demonstrate that CRISPR/Cas9-multiplexing enables key applications, such as combinatorial gene-network analysis, in vivo synthetic lethality screening and chromosome engineering. Negative-selection screening in the pancreas using multiplexed-CRISPR/Cas9 confirms the vulnerability of pancreatic cells to Brca2-inactivation in a Kras-mutant context. We also demonstrate modelling of chromosomal deletions and targeted somatic engineering of inter-chromosomal translocations, offering multifaceted opportunities to study complex structural variation, a hallmark of pancreatic cancer. The low-frequency mosaic pattern of transfection-based CRISPR/Cas9 delivery faithfully recapitulates the stochastic nature of human tumorigenesis, supporting wide applicability for biological/preclinical research.

Indexed as

AnimalsBRCA2 ProteinCarcinogenesisChromosome DeletionCRISPR-Cas SystemsElectroporationGenetic EngineeringGenomeHigh-Throughput Nucleotide SequencingImmunohistochemistryMagnetic Resonance ImagingMiceMutationNeoplasms, ExperimentalPancreasPancreatic NeoplasmsBRCA2 ProteinBRCA2 protein, mouseHras protein, mouseProto-Oncogene Proteins p21(ras)

Identifiers

PMID26916719
PMCPMC4773438
OpenAlexW2300360330

What OpenQuestion holds

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LicenceCC BY
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.