Evidence map›Paper›PMID 42758820›Full record

ArticleScience advances2026

A high-density CRISPR activation platform for mapping cancer dependencies and resistance pathways ex vivo and in vivo.

Sarah T Diepstraten, Yexuan Deng, Margaret A Potts, Amy Heidersbach, Christina König, Kristel M Dorighi, Lin Tai, Andrew J Kueh, Lauren Whelan, Catherine Chang and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Sarah T DiepstratenThe Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Australia.ORCID 0000-0002-1946-5161
Yexuan DengThe Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Australia.
Margaret A PottsThe Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Australia.ORCID 0000-0001-9796-9683
Amy HeidersbachDepartment of Molecular Biology, Genentech Inc., South San Francisco, CA, USA.
Christina KönigThe Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Australia.ORCID 0000-0002-6982-9701
Kristel M DorighiDepartment of Molecular Biology, Genentech Inc., South San Francisco, CA, USA.ORCID 0009-0002-7695-572X
Lin TaiOlivia Newton-John Cancer Research Institute, Heidelberg, Melbourne, Australia.ORCID 0000-0002-3881-8938
Andrew J KuehThe Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Australia.
Lauren WhelanThe Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Australia.
Catherine ChangThe Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Australia.ORCID 0009-0002-9679-6615
Felix BrownThe Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Australia.ORCID 0009-0004-8697-7230
Gemma L KellyThe Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Australia.
Jean-Philippe FortinComputational Sciences, Genentech Inc., South San Francisco, CA, USA.
Benjamin HaleyDepartment of Molecular Biology, Genentech Inc., South San Francisco, CA, USA.ORCID 0000-0002-0074-0020
John E La MarcaThe Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Australia.ORCID 0000-0001-6442-9947
Marco J HeroldThe Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Australia.ORCID 0000-0001-7539-7581

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CRISPR activation (CRISPRa) enables precise up-regulation of gene expression for ex vivo and in vivo applications. However, a lack of scalable, high-coverage tools has limited comprehensive genetic screening in murine models. Here, we introduce Partita, a next-generation mouse whole-genome CRISPRa sgRNA platform, designed for unparalleled efficiency in gene activation studies. Partita uses a high-density targeting strategy, deploying 10 sgRNAs per transcriptional start site, structured into five gene class-specific sublibraries to maximize transcriptional induction. To demonstrate the capabilities of Partita, we performed a series of large-scale screens: an in vitro enrichment/depletion screen, whole-genome CRISPRa screens in a double-hit lymphoma model to uncover resistance factors to proapoptotic drugs (venetoclax, nutlin-3a, and etoposide) and an in vivo screen to identify accelerators of MYC-driven lymphomagenesis. Each experiment revealed both expected and unexpected regulators, with high validation rates. By enabling robust gain-of-function screening, Partita unlocks new avenues for functional genomics and expands the toolkit for discovering key drivers of biological processes across diverse research fields.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsDrug Resistance, NeoplasmNeoplasmsAnimalsGene Expression Regulation, NeoplasticHumansLymphomaMiceProto-Oncogene Proteins c-mycRNA, Guide, CRISPR-Cas SystemsProto-Oncogene Proteins c-mycRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID42758820
PMCPMC13588164

What OpenQuestion holds

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Registered trials

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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.