Evidence map›Paper›PMID 39681701›Full record

ArticleNature biotechnology2025

CRISPR-StAR enables high-resolution genetic screening in complex in vivo models.

Esther C H Uijttewaal, Joonsun Lee, Annika Charlotte Sell, Naomi Botay, Gintautas Vainorius, Maria Novatchkova, Juliane Baar, Jiaye Yang, Tobias Potzler, Sophie van der Leij and 7 more

Abstract read
In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed.

  1. Review
  2. Dual-line Genome-scale CRISPR Screening Enables Robust Target Gene Discovery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Review
  4. Balkan medical journal · 2026
    Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. AI platform for CRISPR functional mapping and function-based drug design.bioRxiv : the preprint server for biology · 2026
    Article
  12. Review
  13. Organoids glimpse: the nexus for diverse tumor heterogeneity.Frontiers in cell and developmental biology · 2026
    Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  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

17 authors.

Esther C H UijttewaalInstitute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Dr. Bohr-Gasse 3, Vienna BioCenter (VBC), Vienna, Austria.ORCID http://orcid.org/0000-0003-3892-2820
Joonsun LeeInstitute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Dr. Bohr-Gasse 3, Vienna BioCenter (VBC), Vienna, Austria.
Annika Charlotte SellInstitute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Dr. Bohr-Gasse 3, Vienna BioCenter (VBC), Vienna, Austria.ORCID http://orcid.org/0009-0006-2272-0094
Naomi BotayInstitute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Dr. Bohr-Gasse 3, Vienna BioCenter (VBC), Vienna, Austria.ORCID http://orcid.org/0009-0001-5469-1252
Gintautas VainoriusInstitute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Dr. Bohr-Gasse 3, Vienna BioCenter (VBC), Vienna, Austria.
Maria NovatchkovaInstitute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Dr. Bohr-Gasse 3, Vienna BioCenter (VBC), Vienna, Austria.
Juliane BaarInstitute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Dr. Bohr-Gasse 3, Vienna BioCenter (VBC), Vienna, Austria.
Jiaye YangInstitute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Dr. Bohr-Gasse 3, Vienna BioCenter (VBC), Vienna, Austria.
Tobias PotzlerInstitute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Dr. Bohr-Gasse 3, Vienna BioCenter (VBC), Vienna, Austria.
Sophie van der LeijInstitute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Dr. Bohr-Gasse 3, Vienna BioCenter (VBC), Vienna, Austria.
Christopher LowdenCentre for Molecular and Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.ORCID http://orcid.org/0000-0002-1839-164X
Julia SinnerInstitute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Dr. Bohr-Gasse 3, Vienna BioCenter (VBC), Vienna, Austria.
Anais ElewautVienna BioCenter PhD Program, University of Vienna and Medical University of Vienna, Vienna, Austria.ORCID http://orcid.org/0009-0009-4064-7320
Milanka GavrilovicInstitute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Dr. Bohr-Gasse 3, Vienna BioCenter (VBC), Vienna, Austria.
Anna ObenaufResearch Institute of Molecular Pathology, Campus-Vienna-Biocenter 1, Vienna BioCenter (VBC), Vienna, Austria.ORCID http://orcid.org/0000-0002-9556-5914
Daniel SchramekCentre for Molecular and Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.ORCID http://orcid.org/0000-0001-9977-2104
Ulrich EllingInstitute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Dr. Bohr-Gasse 3, Vienna BioCenter (VBC), Vienna, Austria. uelling@viveritatx.com.ORCID http://orcid.org/0000-0002-4514-2809

Funding

Terry Fox Research Institute (Institut de Recherche Terry Fox) TFRI Project #1107
6 · The paper itself

Abstract

Pooled genetic screening with CRISPR-Cas9 has enabled genome-wide, high-resolution mapping of genes to phenotypes, but assessing the effect of a given genetic perturbation requires evaluation of each single guide RNA (sgRNA) in hundreds of cells to counter stochastic genetic drift and obtain robust results. However, resolution is limited in complex, heterogeneous models, such as organoids or tumors transplanted into mice, because achieving sufficient representation requires impractical scaling. This is due to bottleneck effects and biological heterogeneity of cell populations. Here we introduce CRISPR-StAR, a screening method that uses internal controls generated by activating sgRNAs in only half the progeny of each cell subsequent to re-expansion of the cell clone. Our method overcomes both intrinsic and extrinsic heterogeneity as well as genetic drift in bottlenecks by generating clonal, single-cell-derived intrinsic controls. We use CRISPR-StAR to identify in-vivo-specific genetic dependencies in a genome-wide screen in mouse melanoma. Benchmarking against conventional screening demonstrates the improved data quality provided by this technology.

Indexed as

CRISPR-Cas SystemsGenetic TestingAnimalsGene EditingHumansMiceRNA, Guide, CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID39681701
PMCPMC12611787

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.