# CRISPR functional genomics

Source: https://onco.cc/technologies/crispr-screens/  
OnCo record `crispr-screens` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Knocking out every gene one at a time in cancer cells to find which ones they cannot live without.

## Summary

CRISPR functional genomics uses pooled sgRNA libraries to knock out, activate, or base-edit every gene in cancer cells, then reads depletion or enrichment by sequencing to find which genes the cells cannot live without. Genome-wide screens across more than 1,000 cell lines (DepMap, Sanger Project Score) map cancer dependencies and synthetic-lethal pairs such as PRMT5/MTAP and WRN/MSI, several of which have become drug programmes. In vivo and immune co-culture screens find immunotherapy resistance genes. The output is a systematic, unbiased dependency map, though cell line artefacts and context specificity mean hits need validation in patient-relevant models. The simple version is a way to test every gene at once and ask which ones a cancer depends on.

## Fields

- Kind: Technology
- Status: established
- Last checked: 2026-09-04
- Principle: Pooled sgRNA libraries; depletion or enrichment measured by sequencing.
- Strengths: Systematic, unbiased dependency maps
- Limitations: Cell line artefacts; context specificity

## Sources

- Defining a Cancer Dependency Map: which genes each cancer cell line cannot live without (Cell 2017): https://doi.org/10.1016/j.cell.2017.06.010

## Connected records

- technologies: [Cancer cell line encyclopedias and dependency maps](https://onco.cc/technologies/cancer-cell-line-encyclopedias/), [Epigenetic editing (durable gene silencing)](https://onco.cc/technologies/epigenetic-editing/), [GEARS and perturbation prediction benchmarks](https://onco.cc/technologies/gears/), [In vivo base and prime editing for cancer](https://onco.cc/technologies/in-vivo-gene-editing-cancer/), [Molecular glue discovery platforms](https://onco.cc/technologies/molecular-glue-platforms/), [Phenom-2 and Recursion OS](https://onco.cc/technologies/phenom-2/), [Programmable DNA-targeting therapeutics](https://onco.cc/technologies/programmable-dna-targeting-therapeutics/), [State (Arc Institute perturbation model)](https://onco.cc/technologies/state-arc/), [Synthetic lethality approaches](https://onco.cc/technologies/synthetic-lethality-approaches/)
- fronts: [Drug Discovery Platforms](https://onco.cc/fronts/drug-discovery/)
- companies: [Algen Biotechnologies](https://onco.cc/companies/algen-biotechnologies/), [Caribou Biosciences](https://onco.cc/companies/caribou/), [Tango Therapeutics](https://onco.cc/companies/tango-therapeutics/)
- ideas: [A drug screen that only rewards killing sleeping cancer cells](https://onco.cc/ideas/idea-bio2-dormancy-selective-screen/), [A pre-competitive consortium to validate or kill academic targets before licensing](https://onco.cc/ideas/idea-fund-target-validation-consortium/), [A synthetic lethality map for every cancer driver in every tissue context](https://onco.cc/ideas/idea-moon-synthetic-lethality-map-every-driver/), [A virtual cancer cell that predicts what a drug will do before you test it](https://onco.cc/ideas/idea-bio1-virtual-cell-perturbation/), [An open atlas of collateral sensitivity for every approved targeted drug](https://onco.cc/ideas/idea-bio1-collateral-sensitivity-atlas/), [An open engine that ranks every drug pair by predicted synergy before anyone runs a trial](https://onco.cc/ideas/idea-tr2-synergy-ranking-engine/), [An open foundation model of the cancer cell trained on perturbation data](https://onco.cc/ideas/idea-data-open-cell-foundation-model/), [An open model of every cancer cell state, built from perturbation atlases](https://onco.cc/ideas/idea-moon-open-cancer-cell-state-model/), [Attack the backup copy when a tumour has lost the original gene](https://onco.cc/ideas/idea-bio1-paralog-synthetic-lethality/), [Barcode patient-derived tumours to watch which clones win under each drug](https://onco.cc/ideas/idea-bio1-barcoded-avatars-clonal-fitness/), [Degraders for the fusion proteins that drive childhood sarcomas](https://onco.cc/ideas/idea-bio1-fusion-tf-degraders/), [Every drug screen includes standard reference compounds whose performance is published](https://onco.cc/ideas/idea-tr2-reference-compound-panels/), [Every resistance mechanism found in a patient must be rebuilt in the laboratory](https://onco.cc/ideas/idea-bio1-reverse-translation-resistance-models/), [Group trials by broken mechanism, not by organ or single mutation](https://onco.cc/ideas/idea-bio2-mechanism-defined-baskets/), [Make bespoke mouse cancer models in weeks with in vivo gene editing](https://onco.cc/ideas/idea-bio1-somatic-crispr-gemms/), [Make in vivo metastasis screens a required step in drug discovery](https://onco.cc/ideas/idea-bio2-metastasis-screen-standard/), [PRMT5/MAT2A synthetic lethality for MTAP-deleted mesothelioma](https://onco.cc/ideas/idea-mtap-prmt5-mesothelioma/), [Self-driving laboratories that run the cancer biology hypothesis loop autonomously](https://onco.cc/ideas/idea-moon-self-driving-cancer-labs/), [Set aside 3% of grant budgets to replicate findings before translation](https://onco.cc/ideas/idea-fund-replication-set-aside/), [Switch off an undruggable oncogene permanently with epigenetic editing](https://onco.cc/ideas/idea-bio1-epigenetic-silencing-in-vivo/), [Test every possible mutation in every cancer gene so no result is 'uncertain'](https://onco.cc/ideas/idea-prev-vus-saturation-editing-consortium/), [Turn chromosomal chaos into a weakness with KIF18A inhibitors](https://onco.cc/ideas/idea-bio1-cin-vulnerability-kif18a/), [WRN inhibitors: a second synthetic-lethal win for mismatch-repair cancers](https://onco.cc/ideas/idea-bio1-wrn-msi-programme/)
- institutions: [Broad Institute of MIT and Harvard](https://onco.cc/institutions/broad-institute/), [Centro Nacional de Investigaciones Oncológicas (CNIO)](https://onco.cc/institutions/cnio/), [Chinese PLA General Hospital](https://onco.cc/institutions/pla-general-hospital/), [Howard Hughes Medical Institute](https://onco.cc/institutions/hhmi/), [Institut Pasteur](https://onco.cc/institutions/institut-pasteur/), [Institute for Stem Cell Science and Regenerative Medicine](https://onco.cc/institutions/instem/), [Max Delbrück Center for Molecular Medicine](https://onco.cc/institutions/mdc-berlin/), [The Jackson Laboratory Cancer Center](https://onco.cc/institutions/jackson-laboratory/), [Walter and Eliza Hall Institute of Medical Research](https://onco.cc/institutions/wehi/), [Weizmann Institute of Science](https://onco.cc/institutions/weizmann/), [Wellcome Sanger Institute](https://onco.cc/institutions/wellcome-sanger/)
- terms: [Cell line](https://onco.cc/terms/cell-line/), [Preclinical](https://onco.cc/terms/preclinical/), [Synthetic lethality](https://onco.cc/terms/synthetic-lethality/), [Virtual cell models and in-silico perturbation screens](https://onco.cc/terms/virtual-cell-models/)
- collections: [DepMap (Cancer Dependency Map)](https://onco.cc/collections/depmap/)
- people: [Christopher R. Vakoc](https://onco.cc/people/christopher-vakoc/), [Feng Zhang](https://onco.cc/people/feng-zhang/), [Francisca Vazquez](https://onco.cc/people/francisca-vazquez/), [Steven E. Artandi](https://onco.cc/people/steven-artandi/), [Todd R. Golub](https://onco.cc/people/todd-golub/), [Waseem Qasim](https://onco.cc/people/waseem-qasim/), [You Lu](https://onco.cc/people/lu-you/)
- bottlenecks: [Lab models that fail to predict what happens in patients](https://onco.cc/bottlenecks/b-preclinical-models/), [Preclinical results do not reproduce](https://onco.cc/bottlenecks/b-reproducibility/), [The valley of death between lab and product](https://onco.cc/bottlenecks/b-translational-valley/), [Too many combinations to test](https://onco.cc/bottlenecks/b-combination-space/)
- targets: [WRN helicase (MSI-high cancers)](https://onco.cc/targets/wrn/)
- key papers: [Defining a Cancer Dependency Map: which genes each cancer cell line cannot live without](https://onco.cc/key-papers/paper-depmap-tsherniak-cell-2017/)
- roadmaps: [Drug discovery roadmap: screening in mice → maps of dependency → designing in silico](https://onco.cc/roadmaps/drug-discovery-roadmap/), [Virtual cell roadmap: from bulk omics to a predictive model of a cancer cell](https://onco.cc/roadmaps/virtual-cell/)
- pathways: [Drivers, passengers & the two-hit model](https://onco.cc/pathways/oncogene-activation-two-hit/), [Synthetic lethality: paired dependencies](https://onco.cc/pathways/synthetic-lethality-map/)

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JSON: https://onco.cc/api/v1/entities/crispr-screens.json