{"entity":{"id":"crispr-screens","kind":"technology","name":"CRISPR functional genomics","aka":[],"tldr":"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.","status":"established","asOf":"2026-09-04","links":[{"label":"Defining a Cancer Dependency Map: which genes each cancer cell line cannot live without (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.06.010"}],"tags":[],"related":["cancer-cell-line-encyclopedias"],"cancers":[],"sections":["drug-discovery"],"technologies":["synthetic-lethality-approaches"],"targets":[],"drugs":[],"companies":["algen-biotechnologies","tango-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Pooled sgRNA libraries; depletion or enrichment measured by sequencing.","strengths":["Systematic, unbiased dependency maps"],"limitations":["Cell line artefacts; context specificity"]},"route":"/technologies/crispr-screens/","neighbours":{"technology":[{"id":"cancer-cell-line-encyclopedias","kind":"technology","name":"Cancer cell line encyclopedias and dependency maps","route":"/technologies/cancer-cell-line-encyclopedias/"},{"id":"epigenetic-editing","kind":"technology","name":"Epigenetic editing (durable gene silencing)","route":"/technologies/epigenetic-editing/"},{"id":"gears","kind":"technology","name":"GEARS and perturbation prediction benchmarks","route":"/technologies/gears/"},{"id":"in-vivo-gene-editing-cancer","kind":"technology","name":"In vivo base and prime editing for cancer","route":"/technologies/in-vivo-gene-editing-cancer/"},{"id":"molecular-glue-platforms","kind":"technology","name":"Molecular glue discovery platforms","route":"/technologies/molecular-glue-platforms/"},{"id":"phenom-2","kind":"technology","name":"Phenom-2 and Recursion OS","route":"/technologies/phenom-2/"},{"id":"programmable-dna-targeting-therapeutics","kind":"technology","name":"Programmable DNA-targeting therapeutics","route":"/technologies/programmable-dna-targeting-therapeutics/"},{"id":"state-arc","kind":"technology","name":"State (Arc Institute perturbation model)","route":"/technologies/state-arc/"},{"id":"synthetic-lethality-approaches","kind":"technology","name":"Synthetic lethality approaches","route":"/technologies/synthetic-lethality-approaches/"}],"section":[{"id":"drug-discovery","kind":"section","name":"Drug Discovery Platforms","route":"/fronts/drug-discovery/"}],"company":[{"id":"algen-biotechnologies","kind":"company","name":"Algen Biotechnologies","route":"/companies/algen-biotechnologies/"},{"id":"caribou","kind":"company","name":"Caribou Biosciences","route":"/companies/caribou/"},{"id":"tango-therapeutics","kind":"company","name":"Tango Therapeutics","route":"/companies/tango-therapeutics/"}],"idea":[{"id":"idea-bio2-dormancy-selective-screen","kind":"idea","name":"A drug screen that only rewards killing sleeping cancer cells","route":"/ideas/idea-bio2-dormancy-selective-screen/"},{"id":"idea-fund-target-validation-consortium","kind":"idea","name":"A pre-competitive consortium to validate or kill academic targets before licensing","route":"/ideas/idea-fund-target-validation-consortium/"},{"id":"idea-moon-synthetic-lethality-map-every-driver","kind":"idea","name":"A synthetic lethality map for every cancer driver in every tissue context","route":"/ideas/idea-moon-synthetic-lethality-map-every-driver/"},{"id":"idea-bio1-virtual-cell-perturbation","kind":"idea","name":"A virtual cancer cell that predicts what a drug will do before you test it","route":"/ideas/idea-bio1-virtual-cell-perturbation/"},{"id":"idea-bio1-collateral-sensitivity-atlas","kind":"idea","name":"An open atlas of collateral sensitivity for every approved targeted drug","route":"/ideas/idea-bio1-collateral-sensitivity-atlas/"},{"id":"idea-tr2-synergy-ranking-engine","kind":"idea","name":"An open engine that ranks every drug pair by predicted synergy before anyone runs a trial","route":"/ideas/idea-tr2-synergy-ranking-engine/"},{"id":"idea-data-open-cell-foundation-model","kind":"idea","name":"An open foundation model of the cancer cell trained on perturbation data","route":"/ideas/idea-data-open-cell-foundation-model/"},{"id":"idea-moon-open-cancer-cell-state-model","kind":"idea","name":"An open model of every cancer cell state, built from perturbation atlases","route":"/ideas/idea-moon-open-cancer-cell-state-model/"},{"id":"idea-bio1-paralog-synthetic-lethality","kind":"idea","name":"Attack the backup copy when a tumour has lost the original gene","route":"/ideas/idea-bio1-paralog-synthetic-lethality/"},{"id":"idea-bio1-barcoded-avatars-clonal-fitness","kind":"idea","name":"Barcode patient-derived tumours to watch which clones win under each drug","route":"/ideas/idea-bio1-barcoded-avatars-clonal-fitness/"},{"id":"idea-bio1-fusion-tf-degraders","kind":"idea","name":"Degraders for the fusion proteins that drive childhood sarcomas","route":"/ideas/idea-bio1-fusion-tf-degraders/"},{"id":"idea-tr2-reference-compound-panels","kind":"idea","name":"Every drug screen includes standard reference compounds whose performance is published","route":"/ideas/idea-tr2-reference-compound-panels/"},{"id":"idea-bio1-reverse-translation-resistance-models","kind":"idea","name":"Every resistance mechanism found in a patient must be rebuilt in the laboratory","route":"/ideas/idea-bio1-reverse-translation-resistance-models/"},{"id":"idea-bio2-mechanism-defined-baskets","kind":"idea","name":"Group trials by broken mechanism, not by organ or single mutation","route":"/ideas/idea-bio2-mechanism-defined-baskets/"},{"id":"idea-bio1-somatic-crispr-gemms","kind":"idea","name":"Make bespoke mouse cancer models in weeks with in vivo gene editing","route":"/ideas/idea-bio1-somatic-crispr-gemms/"},{"id":"idea-bio2-metastasis-screen-standard","kind":"idea","name":"Make in vivo metastasis screens a required step in drug discovery","route":"/ideas/idea-bio2-metastasis-screen-standard/"},{"id":"idea-mtap-prmt5-mesothelioma","kind":"idea","name":"PRMT5/MAT2A synthetic lethality for MTAP-deleted mesothelioma","route":"/ideas/idea-mtap-prmt5-mesothelioma/"},{"id":"idea-moon-self-driving-cancer-labs","kind":"idea","name":"Self-driving laboratories that run the cancer biology hypothesis loop autonomously","route":"/ideas/idea-moon-self-driving-cancer-labs/"},{"id":"idea-fund-replication-set-aside","kind":"idea","name":"Set aside 3% of grant budgets to replicate findings before translation","route":"/ideas/idea-fund-replication-set-aside/"},{"id":"idea-bio1-epigenetic-silencing-in-vivo","kind":"idea","name":"Switch off an undruggable oncogene permanently with epigenetic editing","route":"/ideas/idea-bio1-epigenetic-silencing-in-vivo/"},{"id":"idea-prev-vus-saturation-editing-consortium","kind":"idea","name":"Test every possible mutation in every cancer gene so no result is 'uncertain'","route":"/ideas/idea-prev-vus-saturation-editing-consortium/"},{"id":"idea-bio1-cin-vulnerability-kif18a","kind":"idea","name":"Turn chromosomal chaos into a weakness with KIF18A inhibitors","route":"/ideas/idea-bio1-cin-vulnerability-kif18a/"},{"id":"idea-bio1-wrn-msi-programme","kind":"idea","name":"WRN inhibitors: a second synthetic-lethal win for mismatch-repair cancers","route":"/ideas/idea-bio1-wrn-msi-programme/"}],"institution":[{"id":"broad-institute","kind":"institution","name":"Broad Institute of MIT and Harvard","route":"/institutions/broad-institute/"},{"id":"cnio","kind":"institution","name":"Centro Nacional de Investigaciones Oncológicas (CNIO)","route":"/institutions/cnio/"},{"id":"pla-general-hospital","kind":"institution","name":"Chinese PLA General Hospital","route":"/institutions/pla-general-hospital/"},{"id":"hhmi","kind":"institution","name":"Howard Hughes Medical Institute","route":"/institutions/hhmi/"},{"id":"institut-pasteur","kind":"institution","name":"Institut Pasteur","route":"/institutions/institut-pasteur/"},{"id":"instem","kind":"institution","name":"Institute for Stem Cell Science and Regenerative Medicine","route":"/institutions/instem/"},{"id":"mdc-berlin","kind":"institution","name":"Max Delbrück Center for Molecular Medicine","route":"/institutions/mdc-berlin/"},{"id":"jackson-laboratory","kind":"institution","name":"The Jackson Laboratory Cancer Center","route":"/institutions/jackson-laboratory/"},{"id":"wehi","kind":"institution","name":"Walter and Eliza Hall Institute of Medical Research","route":"/institutions/wehi/"},{"id":"weizmann","kind":"institution","name":"Weizmann Institute of Science","route":"/institutions/weizmann/"},{"id":"wellcome-sanger","kind":"institution","name":"Wellcome Sanger Institute","route":"/institutions/wellcome-sanger/"}],"term":[{"id":"cell-line","kind":"term","name":"Cell line","route":"/terms/cell-line/"},{"id":"preclinical","kind":"term","name":"Preclinical","route":"/terms/preclinical/"},{"id":"synthetic-lethality","kind":"term","name":"Synthetic lethality","route":"/terms/synthetic-lethality/"},{"id":"virtual-cell-models","kind":"term","name":"Virtual cell models and in-silico perturbation screens","route":"/terms/virtual-cell-models/"}],"collection":[{"id":"depmap","kind":"collection","name":"DepMap (Cancer Dependency Map)","route":"/collections/depmap/"}],"person":[{"id":"christopher-vakoc","kind":"person","name":"Christopher R. Vakoc","route":"/people/christopher-vakoc/"},{"id":"feng-zhang","kind":"person","name":"Feng Zhang","route":"/people/feng-zhang/"},{"id":"francisca-vazquez","kind":"person","name":"Francisca Vazquez","route":"/people/francisca-vazquez/"},{"id":"steven-artandi","kind":"person","name":"Steven E. Artandi","route":"/people/steven-artandi/"},{"id":"todd-golub","kind":"person","name":"Todd R. Golub","route":"/people/todd-golub/"},{"id":"waseem-qasim","kind":"person","name":"Waseem Qasim","route":"/people/waseem-qasim/"},{"id":"lu-you","kind":"person","name":"You Lu","route":"/people/lu-you/"}],"bottleneck":[{"id":"b-preclinical-models","kind":"bottleneck","name":"Lab models that fail to predict what happens in patients","route":"/bottlenecks/b-preclinical-models/"},{"id":"b-reproducibility","kind":"bottleneck","name":"Preclinical results do not reproduce","route":"/bottlenecks/b-reproducibility/"},{"id":"b-translational-valley","kind":"bottleneck","name":"The valley of death between lab and product","route":"/bottlenecks/b-translational-valley/"},{"id":"b-combination-space","kind":"bottleneck","name":"Too many combinations to test","route":"/bottlenecks/b-combination-space/"}],"target":[{"id":"wrn","kind":"target","name":"WRN helicase (MSI-high cancers)","route":"/targets/wrn/"}],"paper":[{"id":"paper-depmap-tsherniak-cell-2017","kind":"paper","name":"Defining a Cancer Dependency Map: which genes each cancer cell line cannot live without","route":"/key-papers/paper-depmap-tsherniak-cell-2017/"}],"roadmap":[{"id":"drug-discovery-roadmap","kind":"roadmap","name":"Drug discovery roadmap: screening in mice → maps of dependency → designing in silico","route":"/roadmaps/drug-discovery-roadmap/"},{"id":"virtual-cell","kind":"roadmap","name":"Virtual cell roadmap: from bulk omics to a predictive model of a cancer cell","route":"/roadmaps/virtual-cell/"}],"pathway":[{"id":"oncogene-activation-two-hit","kind":"pathway","name":"Drivers, passengers & the two-hit model","route":"/pathways/oncogene-activation-two-hit/"},{"id":"synthetic-lethality-map","kind":"pathway","name":"Synthetic lethality: paired dependencies","route":"/pathways/synthetic-lethality-map/"}]}}