{"id":101954,"date":"2025-07-29T11:35:11","date_gmt":"2025-07-29T11:35:11","guid":{"rendered":"https:\/\/www.europesays.com\/us\/101954\/"},"modified":"2025-07-29T11:35:11","modified_gmt":"2025-07-29T11:35:11","slug":"methods-and-applications-of-in-vivo-crispr-screening","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/us\/101954\/","title":{"rendered":"Methods and applications of in vivo CRISPR screening"},"content":{"rendered":"
  • \n

    Auton, A. et al. A global reference for human genetic variation. Nature 526<\/b>, 68\u201374 (2015).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Garc\u00eda-Garc\u00eda, M. J. in Animal Models of Human Birth Defects (ed. Liu, A.) 1\u201338 (Springer, 2020).<\/p>\n<\/li>\n

  • \n

    Patton, E. E. & Zon, L. I. The art and design of genetic screens: zebrafish. Nat. Rev. Genet. 2<\/b>, 956\u2013966 (2001).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    St Johnston, D. The art and design of genetic screens: Drosophila melanogaster. Nat. Rev. Genet. 3<\/b>, 176\u2013188 (2002).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Kile, B. T. & Hilton, D. J. The art and design of genetic screens: mouse. Nat. Rev. Genet. 6<\/b>, 557\u2013567 (2005).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Boutros, M. & Ahringer, J. The art and design of genetic screens: RNA interference. Nat. Rev. Genet. 9<\/b>, 554\u2013566 (2008).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Anzalone, A. V., Koblan, L. W. & Liu, D. R. Genome editing with CRISPR\u2013Cas nucleases, base editors, transposases and prime editors. Nat. Biotechnol. 38<\/b>, 824\u2013844 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Nakamura, M., Gao, Y., Dominguez, A. A. & Qi, L. S. CRISPR technologies for precise epigenome editing. Nat. Cell Biol. 23<\/b>, 11\u201322 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Villiger, L. et al. CRISPR technologies for genome, epigenome and transcriptome editing. Nat. Rev. Mol. Cell Biol. 25<\/b>, 464\u2013487 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Evers, B. et al. CRISPR knockout screening outperforms shRNA and CRISPRi in identifying essential genes. Nat. Biotechnol. 34<\/b>, 631\u2013633 (2016).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Michels, B. E. et al. Pooled in vitro and in vivo CRISPR\u2013Cas9 screening identifies tumor suppressors in human colon organoids. Cell Stem Cell 26<\/b>, 782\u2013792.e7 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Hart, T. et al. High-resolution CRISPR screens reveal fitness genes and genotype-specific cancer liabilities. Cell 163<\/b>, 1515\u20131526 (2015).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Parnas, O. et al. A genome-wide CRISPR screen in primary immune cells to dissect regulatory networks. Cell 162<\/b>, 675\u2013686 (2015).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Li, C. et al. Single-cell brain organoid screening identifies developmental defects in autism. Nature 621<\/b>, 373\u2013380 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Fleck, J. S. et al. Inferring and perturbing cell fate regulomes in human brain organoids. Nature 621<\/b>, 365\u2013372 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Bock, C. et al. High-content CRISPR screening. Nat. Rev. Methods Prim. 2022 2:1 2<\/b>, 1\u201323 (2022). This review summarizes the use of CRISPR tools for pooled genetic screening.<\/b><\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Cunningham, D. & You, Z. In vitro and in vivo model systems used in prostate cancer research. J. Biol. Methods 2<\/b>, e17 (2015).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Kipp, M. et al. Experimental in vivo and in vitro models of multiple sclerosis: EAE and beyond. Mult. Scler. Relat. Disord. 1<\/b>, 15\u201328 (2012).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Miller, T. E. et al. Transcription elongation factors represent in vivo cancer dependencies in glioblastoma. Nature 547<\/b>, 355\u2013359 (2017).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zhao, H. et al. Genome-wide fitness gene identification reveals Roquin as a potent suppressor of CD8 T cell expansion and anti-tumor immunity. Cell Rep. 37<\/b>, 110083 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zhu, X. G. et al. Functional genomics in vivo reveal metabolic dependencies of pancreatic cancer cells. Cell Metab. 33<\/b>, 211\u2013221.e6 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Mercier, F. E. et al. In vivo genome-wide CRISPR screening in murine acute myeloid leukemia uncovers microenvironmental dependencies. Blood Adv. 6<\/b>, 5072\u20135084 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zender, L. et al. An oncogenomics-based in vivo RNAi screen identifies tumor suppressors in liver cancer. Cell 135<\/b>, 852\u2013864 (2008).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zuber, J. et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 478<\/b>, 524\u2013528 (2011).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wuestefeld, T. et al. A direct in vivo RNAi screen identifies MKK4 as a key regulator of liver regeneration. Cell 153<\/b>, 389\u2013401 (2013).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Miller, P. G. et al. In vivo RNAi screening identifies a leukemia-specific dependence on integrin \u03b23 signaling. Cancer Cell 24<\/b>, 45\u201358 (2013).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Beronja, S. et al. RNAi screens in mice identify physiological regulators of oncogenic growth. Nature 501<\/b>, 185\u2013190 (2013).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Morris, J. A., Sun, J. S. & Sanjana, N. E. Next-generation forward genetic screens: uniting high-throughput perturbations with single-cell analysis. Trends Genet. 40<\/b>, 118\u2013133 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Thyme, S. B. et al. Phenotypic landscape of schizophrenia-associated genes defines candidates and their shared functions. Cell 177<\/b>, 478\u2013491.e20 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Meltzer, H. et al. Tissue-specific (ts)CRISPR as an efficient strategy for in vivo screening in Drosophila. Nat. Commun. 10<\/b>, 2113 (2019).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wang, Y. et al. Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFN\u03b3-activated murine macrophages. Nat. Commun. 11<\/b>, 5258 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Tachibana, Y., Hashizaki, E., Sasai, M. & Yamamoto, M. Host genetics highlights IFN-\u03b3-dependent Toxoplasma genes encoding secreted and non-secreted virulence factors in in vivo CRISPR screens. Cell Rep. 42<\/b>, 112592 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Hansen, S. L. et al. An organoid-based CRISPR\u2013Cas9 screen for regulators of intestinal epithelial maturation and cell fate. Sci. Adv. 9<\/b>, eadg4055 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Geurts, M. H. & Clevers, H. CRISPR engineering in organoids for gene repair and disease modelling. Nat. Rev. Bioeng. 1<\/b>, 32\u201345 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Pandelakis, M., Delgado, E. & Ebrahimkhani, M. R. CRISPR-based synthetic transcription factors in vivo: the future of therapeutic cellular programming. Cell Syst. 10<\/b>, 1\u201314 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Bowling, S. et al. An engineered CRISPR\u2013Cas9 mouse line for simultaneous readout of lineage histories and gene expression profiles in single cells. Cell 181<\/b>, 1410\u20131422.e27 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Li, L. et al. A mouse model with high clonal barcode diversity for joint lineage, transcriptomic, and epigenomic profiling in single cells. Cell 186<\/b>, 5183\u20135199.e22 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Liu, B. et al. Large-scale multiplexed mosaic CRISPR perturbation in the whole organism. Cell 185<\/b>, 3008\u20133024.e16 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Braun, C. J., Adames, A. C., Saur, D. & Rad, R. Tutorial: design and execution of CRISPR in vivo screens. Nat. Protoc. 17<\/b>, 1903\u20131925 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chen, S. et al. Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis. Cell 160<\/b>, 1246\u20131260 (2015).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Manguso, R. T. et al. In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target. Nature 547<\/b>, 413\u2013418 (2017).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zhang, Z. et al. Genome-wide CRISPR\/Cas9 screening for drug resistance in tumors. Front. Pharmacol. 14<\/b>, 1284610 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chow, R. D. & Chen, S. Cancer CRISPR screens. Vivo. Trends Cancer 4<\/b>, 349\u2013358 (2018).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Rodriguez-Fraticelli, A. E. et al. Single-cell lineage tracing unveils a role for TCF15 in haematopoiesis. Nature 583<\/b>, 585\u2013589 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lara-Astiaso, D. et al. In vivo screening characterizes chromatin factor functions during normal and malignant hematopoiesis. Nat. Genet. 55<\/b>, 1542\u20131554 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Tran, N. T. et al. In vivo CRISPR\/Cas9-mediated screen reveals a critical function of TFDP1 and E2F4 transcription factors in hematopoiesis. Leukemia 38<\/b>, 2003\u20132015 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Dong, M. B. et al. Systematic immunotherapy target discovery using genome-scale in vivo CRISPR screens in CD8 T cells. Cell 178<\/b>, 1189\u20131204.e23 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wei, J. et al. Targeting REGNASE-1 programs long-lived effector T cells for cancer therapy. Nature 576<\/b>, 471\u2013476 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Huang, H. et al. In vivo CRISPR screening reveals nutrient signaling processes underpinning CD8+ T cell fate decisions. Cell 184<\/b>, 1245\u20131261.e21 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chen, Z. et al. In vivo CD8+ T cell CRISPR screening reveals control by Fli1 in infection and cancer. Cell 184<\/b>, 1262\u20131280.e22 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Belk, J. A. et al. Genome-wide CRISPR screens of T cell exhaustion identify chromatin remodeling factors that limit T cell persistence. Cancer Cell 40<\/b>, 768\u2013786.e7 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Baxter, A. E. et al. The SWI\/SNF chromatin remodeling complexes BAF and PBAF differentially regulate epigenetic transitions in exhausted CD8+ T cells. Immunity 56<\/b>, 1320\u20131340.e10 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zhou, P. et al. Single-cell CRISPR screens in vivo map T cell fate regulomes in cancer. Nature 624<\/b>, 154\u2013163 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Sutra Del Galy, A. et al. In vivo genome-wide CRISPR screens identify SOCS1 as intrinsic checkpoint of CD4+ TH1 cell response. Sci. Immunol. 6<\/b>, eabe8219 (2021).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Kendirli, A. et al. A genome-wide in vivo CRISPR screen identifies essential regulators of T cell migration to the CNS in a multiple sclerosis model. Nat. Neurosci. 26<\/b>, 1713\u20131725 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Huang, B. et al. In vivo CRISPR screens reveal a HIF-1\u03b1\u2013mTOR-network regulates T follicular helper versus TH1 cells. Nat. Commun. 13<\/b>, 805 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Peng, L. et al. In vivo AAV\u2013SB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy. Nat. Biotechnol. 43<\/b>, 752\u2013761 (2025).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Fu, G. et al. Metabolic control of TFH cells and humoral immunity by phosphatidylethanolamine. Nature 595<\/b>, 724\u2013729 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zhou, W., Gao, F., Romero-Wolf, M., Jo, S. & Rothenberg, E. V. Single-cell deletion analyses show control of pro-T cell developmental speed and pathways by Tcf7, Spi1, Gata3, Bcl11a, Erg, and Bcl11b. Sci. Immunol. 7<\/b>, eabm1920 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    LaFleur, M. W. et al. A CRISPR\u2013Cas9 delivery system for in vivo screening of genes in the immune system. Nat. Commun. 10<\/b>, 1668 (2019).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Cai, E. P. et al. Genome-scale in vivo CRISPR screen identifies RNLS as a target for beta cell protection in type 1 diabetes. Nat. Metab. 2<\/b>, 934\u2013945 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Sintov, E. et al. Whole-genome CRISPR screening identifies genetic manipulations to reduce immune rejection of stem cell-derived islets. Stem Cell Rep. 17<\/b>, 1976\u20131990 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J. & Clarke, M. F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl Acad. Sci. USA 100<\/b>, 3983\u20133988 (2003).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Nguyen, L. V. et al. DNA barcoding reveals diverse growth kinetics of human breast tumour subclones in serially passaged xenografts. Nat. Commun. 5<\/b>, 5871 (2014).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Michlits, G. et al. CRISPR-UMI: single-cell lineage tracing of pooled CRISPR\u2013Cas9 screens. Nat. Methods 14<\/b>, 1191\u20131197 (2017).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Merino, D. et al. Barcoding reveals complex clonal behavior in patient-derived xenografts of metastatic triple negative breast cancer. Nat. Commun. 10<\/b>, 766 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Eirew, P. et al. Accurate determination of CRISPR-mediated gene fitness in transplantable tumours. Nat. Commun. 13<\/b>, 4534 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Rogers, Z. N. et al. A quantitative and multiplexed approach to uncover the fitness landscape of tumor suppression in vivo. Nat. Methods 14<\/b>, 737\u2013742 (2017).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Schmierer, B. et al. CRISPR\/Cas9 screening using unique molecular identifiers. Mol. Syst. Biol. 13<\/b>, 945 (2017).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Esk, C. et al. A human tissue screen identifies a regulator of ER secretion as a brain-size determinant. Science 370<\/b>, 935\u2013941 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Uijttewaal, E. C. H. et al. CRISPR\u2013StAR enables high-resolution genetic screening in complex in vivo models. Nat. Biotechnol. https:\/\/doi.org\/10.1038\/s41587-024-02512-9<\/a> (2024).<\/p>\n<\/li>\n

  • \n

    Shirley, J. L., de Jong, Y. P., Terhorst, C. & Herzog, R. W. Immune responses to viral gene therapy vectors. Mol. Ther. 28<\/b>, 709\u2013722 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Weber, J. et al. CRISPR\/Cas9 somatic multiplex-mutagenesis for high-throughput functional cancer genomics in mice. Proc. Natl Acad. Sci. USA 112<\/b>, 13982\u201313987 (2015).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Xu, C. et al. piggyBac mediates efficient in vivo CRISPR library screening for tumorigenesis in mice. Proc. Natl Acad. Sci. USA 114<\/b>, 722\u2013727 (2017).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wang, G. et al. Mapping a functional cancer genome atlas of tumor suppressors in mouse liver using AAV\u2013CRISPR-mediated direct in vivo screening. Sci. Adv. 4<\/b>, eaao5508 (2018). This article demonstrates the use of molecular inversion probes<\/b>.<\/b><\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wangensteen, K. J. et al. Combinatorial genetics in liver repopulation and carcinogenesis with a in vivo CRISPR activation platform. Hepatology 68<\/b>, 663\u2013676 (2018).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wang, G. et al. CRISPR\u2013GEMM pooled mutagenic screening identifies KMT2D as a major modulator of immune checkpoint blockade. Cancer Discov. 10<\/b>, 1912\u20131933 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Keys, H. R. & Knouse, K. A. Genome-scale CRISPR screening in a single mouse liver. Cell Genomics 2<\/b>, 100217 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Jia, Y. et al. In vivo CRISPR screening identifies BAZ2 chromatin remodelers as druggable regulators of mammalian liver regeneration. Cell Stem Cell 29<\/b>, 372\u2013385.e8 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wang, Z. et al. Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease. Cell 186<\/b>, 1968\u20131984.e20 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chen, Y. et al. Acute liver steatosis translationally controls the epigenetic regulator MIER1 to promote liver regeneration in a study with male mice. Nat. Commun. 14<\/b>, 1521 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Borrelli, C. et al. In vivo interaction screening reveals liver-derived constraints to metastasis. Nature 632<\/b>, 411\u2013418 632 (2024). This study highlights in vivo CRISPR screens to probe cell\u2013cell interactions; the study combines direct in vivo CRISPRa screening in liver hepatocytes with a xenograft tumour model.<\/b><\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chow, R. D. et al. AAV-mediated direct in vivo CRISPR screen identifies functional suppressors in glioblastoma. Nat. Neurosci. 20<\/b>, 1329\u20131341 (2017). This study demonstrates the use of target-capture probes.<\/b><\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Jin, X. et al. In vivo Perturb-seq reveals neuronal and glial abnormalities associated with autism risk genes. Science 370<\/b>, eaaz6063 (2020). This article describes the application of Perturb-seq in utero to study autism spectrum disorder-related genes.<\/b><\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wertz, M. H. et al. Genome-wide in vivo CNS screening identifies genes that modify CNS neuronal survival and mHTT toxicity. Neuron 106<\/b>, 76\u201389.e8 (2020). This paper reports a non-liver genome-scale depletion screen and discusses inconsistencies with shRNA screens and challenges of scale.<\/b><\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Santinha, A. J. et al. Transcriptional linkage analysis with in vivo AAV-Perturb-seq. Nature 622<\/b>, 367\u2013375 (2023). This paper introduces AAV-Perturb-seq for direct in vivo single-cell CRISPR screens in adult animals.<\/b><\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zheng, X. et al. Massively parallel in vivo Perturb-seq reveals cell-type-specific transcriptional networks in cortical development. Cell 187<\/b>, 3236\u20133248.e21 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Ruetz, T. J. et al. CRISPR\u2013Cas9 screens reveal regulators of ageing in neural stem cells. Nature 634<\/b>, 1150\u20131159 (2024). This article describes an in vivo CRISPR screen that provides insight into cell migration in a non-tumour model<\/b><\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Dervovic, D. et al. In vivo CRISPR screens reveal Serpinb9 and Adam2 as regulators of immune therapy response in lung cancer. Nat. Commun. 14<\/b>, 3150 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Tang, R. et al. Multiplexed screens identify RAS paralogues HRAS and NRAS as suppressors of KRAS-driven lung cancer growth. Nat. Cell Biol. 25<\/b>, 159\u2013169 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Maresch, R. et al. Multiplexed pancreatic genome engineering and cancer induction by transfection-based CRISPR\/Cas9 delivery in mice. Nat. Commun. 7<\/b>, 10770 (2016).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Martinez, S. et al. In vivo CRISPR screens reveal SCAF1 and USP15 as drivers of pancreatic cancer. Nat. Commun. 15<\/b>, 5266 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    VanDusen, N. J. et al. Massively parallel in vivo CRISPR screening identifies RNF20\/40 as epigenetic regulators of cardiomyocyte maturation. Nat. Commun. 12<\/b>, 4442 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Noguchi, Y. et al. In vivo CRISPR screening directly targeting testicular cells. Cell Genomics 4<\/b>, 100510 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Loganathan, S. K. et al. Rare driver mutations in head and neck squamous cell carcinomas converge on NOTCH signaling. Science 367<\/b>, 1264\u20131269 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Renz, P. F. et al. In vivo single-cell CRISPR uncovers distinct TNF programmes in tumour evolution. Nature 632<\/b>, 419\u2013428 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Langille, E. et al. Loss of epigenetic regulation disrupts lineage integrity, induces aberrant alveogenesis, and promotes breast cancer. Cancer Discov. 12<\/b>, 2930\u20132953 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Schramek, D. et al. Aneuploidy drives the acquisition of cancer-specific driver genes. Preprint at Res. Sq. https:\/\/doi.org\/10.21203\/rs.3.rs-4941895\/v1<\/a> (2024).<\/p>\n<\/li>\n

  • \n

    Li, J. et al. Epigenetic and transcriptional control of the epidermal growth factor receptor regulates the tumor immune microenvironment in pancreatic cancer. Cancer Discov. 11<\/b>, 736\u2013753 (2021).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Dubrot, J. et al. In vivo CRISPR screens reveal the landscape of immune evasion pathways across cancer. Nat. Immunol. 23<\/b>, 1495\u20131506 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Ishizuka, J. J. et al. Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade. Nature 565<\/b>, 43\u201348 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Li, F. et al. In vivo epigenetic CRISPR screen identifies asf1a as an immunotherapeutic target in Kras-mutant lung adenocarcinoma. Cancer Discov. 10<\/b>, 270\u2013287 (2020).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Griffin, G. K. et al. Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity. Nature 595<\/b>, 309\u2013314 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Tang, K. et al. Cas12a-knock-in mice for multiplexed genome editing, disease modelling and immune-cell engineering. Nat. Biomed. Eng. https:\/\/doi.org\/10.1038\/s41551-025-01371-2<\/a> (2025).<\/p>\n<\/li>\n

  • \n

    Katti, A. et al. Generation of precision preclinical cancer models using regulated in vivo base editing. Nat. Biotechnol. 42<\/b>, 437\u2013447 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Ely, Z. A. et al. A prime editor mouse to model a broad spectrum of somatic mutations in vivo. Nat. Biotechnol. 42<\/b>, 424\u2013436 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    An, M. et al. Engineered virus-like particles for transient delivery of prime editor ribonucleoprotein complexes in vivo. Nat. Biotechnol. 42<\/b>, 1526\u20131537 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Ogden, P. J., Kelsic, E. D., Sinai, S. & Church, G. M. Comprehensive AAV capsid fitness landscape reveals a viral gene and enables machine-guided design. Science 366<\/b>, 1139\u20131143 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Denisenko, E. et al. Systematic assessment of tissue dissociation and storage biases in single-cell and single-nucleus RNA-seq workflows. Genome Biol. 21<\/b>, 130 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Bakken, T. E. et al. Single-nucleus and single-cell transcriptomes compared in matched cortical cell types. PLoS One 13<\/b>, e0209648 (2018).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Adamson, B. et al. A multiplexed single-cell CRISPR screening platform enables systematic dissection of the unfolded protein response. Cell 167<\/b>, 1867\u20131882.e21 (2016).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Dixit, A. et al. Perturb-seq: dissecting molecular circuits with scalable single-cell RNA profiling pool. genet. screens. Cell 167<\/b>, 1853\u20131866.e17 (2016).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Jaitin, D. A. et al. Dissecting immune circuits by linking CRISPR-pooled screens with single-cell RNA-seq. Cell 167<\/b>, 1883\u20131896.e15 (2016).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Datlinger, P. et al. Pooled CRISPR screening with single-cell transcriptome readout. Nat. Methods 14<\/b>, 297\u2013301 (2017).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Xie, S., Duan, J., Li, B., Zhou, P. & Hon, G. C. Multiplexed engineering and analysis of combinatorial enhancer activity in single cells. Mol. Cell 66<\/b>, 285\u2013299.e5 (2017).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Schraivogel, D. et al. Targeted Perturb-seq enables genome-scale genetic screens in single cells. Nat. Methods 17<\/b>, 629\u2013635 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Liscovitch-Brauer, N. et al. Profiling the genetic determinants of chromatin accessibility with scalable single-cell CRISPR screens. Nat. Biotechnol. 39<\/b>, 1270\u20131277 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Pierce, S. E., Granja, J. M. & Greenleaf, W. J. High-throughput single-cell chromatin accessibility CRISPR screens enable unbiased identification of regulatory networks in cancer. Nat. Commun. 12<\/b>, 2969 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Rubin, A. J. et al. Coupled single-cell CRISPR screening and epigenomic profiling reveals causal gene regulatory networks. Cell 176<\/b>, 361\u2013376.e17 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Mimitou, E. P. et al. Multiplexed detection of proteins, transcriptomes, clonotypes and CRISPR perturbations in single cells. Nat. Methods 16<\/b>, 409\u2013412 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Frangieh, C. J. et al. Multimodal pooled Perturb-CITE-seq screens in patient models define mechanisms of cancer immune evasion. Nat. Genet. 53<\/b>, 332\u2013341 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wroblewska, A. et al. Protein barcodes enable high-dimensional single-cell CRISPR screens. Cell 175<\/b>, 1141\u20131155.e16 (2018).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Li, K., Ouyang, M., Zhan, J. & Tian, R. CRISPR-based functional genomics screening in human-pluripotent-stem-cell-derived cell types. Cell Genomics 3<\/b>, 100300 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Alda-Catalinas, C. et al. A single-cell transcriptomics CRISPR-activation screen identifies epigenetic regulators of the zygotic genome activation program. cels 11<\/b>, 25\u201341.e9 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Guo, Y. & Zhao, X. CRISPR-based genetic screens in human pluripotent stem cells derived neurons and brain organoids. Cell Tissue Res. 399<\/b>, 1\u20138 (2025).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wang, D. et al. CRISPR screening of CAR T cells and cancer stem cells reveals critical dependencies for cell-based therapies. Cancer Discov. 11<\/b>, 1192\u20131211 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wang, W. & Wang, X. Single-cell CRISPR screening in drug resistance. Cell Biol. Toxicol. 33<\/b>, 207\u2013210 (2017).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Binan, L. et al. Simultaneous CRISPR screening and spatial transcriptomics reveal intracellular, intercellular, and functional transcriptional circuits. Cell 188<\/b>, 2141\u20132158.e18 (2025).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Feldman, D. et al. Optical pooled screens in human Cells. Cell 179<\/b>, 787\u2013799.e17 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Saunders, R. A. et al. Perturb-Multimodal: a platform for pooled genetic screens with imaging and sequencing in intact mammalian tissue. Cell https:\/\/doi.org\/10.1016\/j.cell.2025.05.022<\/a> (2025)<\/p>\n<\/li>\n

  • \n

    Baysoy, A. et al. Spatially resolved in vivo CRISPR screen sequencing via perturb-DBiT. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2024.11.18.624106<\/a> (2024).<\/p>\n<\/li>\n

  • \n

    Kudo, T. et al. Multiplexed, image-based pooled screens in primary cells and tissues with PerturbView. Nat. Biotechnol. 43<\/b>, 1091\u20131100 (2025). This study implements the T7 promoter for robust in situ gRNA detection in spatial screens.<\/b><\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Dhainaut, M. et al. Spatial CRISPR genomics identifies regulators of the tumor microenvironment. Cell 185<\/b>, 1223\u20131239.e20 (2022). This article describes a spatial screen and introduces ProCodes for reading perturbations with multiplex protein imaging.<\/b><\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Mollaoglu, G. et al. Ovarian cancer-derived IL-4 promotes immunotherapy resistance. Cell 187<\/b>, 7492\u20137510.e22 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Behr, M., Zhou, J., Xu, B. & Zhang, H. In vivo delivery of CRISPR\u2013Cas9 therapeutics: progress and challenges. Acta Pharm. Sin. B 11<\/b>, 2150\u20132171 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Platt, R. J. et al. CRISPR\u2013Cas9 knockin mice for genome editing and cancer modeling. Cell 159<\/b>, 440\u2013455 (2014). This study produced the first mice carrying a knock-in allele of a Cas effector protein.<\/b><\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chu, V. T. et al. Efficient generation of Rosa26 knock-in mice using CRISPR\/Cas9 in C57BL\/6 zygotes. BMC Biotechnol. 16<\/b>, 4 (2016).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Gemberling, M. P. et al. Transgenic mice for in vivo epigenome editing with CRISPR-based systems. Nat. Methods 18<\/b>, 965\u2013974 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Li, K. et al. Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing. Nat. Commun. 11<\/b>, 485 (2020).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zhou, H. et al. In vivo simultaneous transcriptional activation of multiple genes in the brain using CRISPR\u2013dCas9-activator transgenic mice. Nat. Neurosci. 21<\/b>, 440\u2013446 (2018).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Li, J., Zhu, D., Hu, S. & Nie, Y. CRISPR\u2013CasRx knock-in mice for RNA degradation. Sci. China Life Sci. 65<\/b>, 2248\u20132256 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wessels, H.-H. et al. Efficient combinatorial targeting of RNA transcripts in single cells with Cas13 RNA Perturb-seq. Nat. Methods 20<\/b>, 86\u201394 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Hebert, J. D. et al. Efficient and multiplexed somatic genome editing with Cas12a mice. Nat. Biomed. Eng. https:\/\/doi.org\/10.1038\/s41551-025-01407-7<\/a> (2025).<\/p>\n<\/li>\n

  • \n

    Klingler, E. et al. Temporal controls over inter-areal cortical projection neuron fate diversity. Nature 599<\/b>, 453\u2013457 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Luther, D. C., Lee, Y. W., Nagaraj, H., Scaletti, F. & Rotello, V. M. Delivery approaches for CRISPR\/Cas9 therapeutics in vivo: advances and challenges. Expert. Opin. Drug. Deliv. 15<\/b>, 905\u2013913 (2018).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wilbie, D., Walther, J. & Mastrobattista, E. Delivery aspects of CRISPR\/Cas for in vivo genome editing. Acc. Chem. Res. 52<\/b>, 1555\u20131564 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Duverg\u00e9, A. & Negroni, M. Pseudotyping lentiviral vectors: when the clothes make the virus. Viruses 12<\/b>, 1311 (2020).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Hindi, S. M. et al. Enveloped viruses pseudotyped with mammalian myogenic cell fusogens target skeletal muscle for gene delivery. Cell 186<\/b>, 2062\u20132077.e17 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wang, D., Tai, P. W. L. & Gao, G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat. Rev. Drug. Discov. 18<\/b>, 358\u2013378 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lin, R. et al. Directed evolution of adeno-associated virus for efficient gene delivery to microglia. Nat. Methods 19<\/b>, 976\u2013985 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Deverman, B. E. et al. Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain. Nat. Biotechnol. 34<\/b>, 204\u2013209 (2016).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Riedmayr, L. M. et al. mRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy. Nat. Commun. 14<\/b>, 6578 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chew, W. L. et al. A multi-functional AAV\u2013CRISPR\u2013Cas9 and its host response. Nat. Methods 13<\/b>, 868\u2013874 (2016).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Ye, L. et al. In vivo CRISPR screening in CD8 T cells with AAV\u2013sleeping beauty hybrid vectors identifies membrane targets for improving immunotherapy for glioblastoma. Nat. Biotechnol. 37<\/b>, 1302\u20131313 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zengel, J. et al. Hardwiring tissue-specific AAV transduction in mice through engineered receptor expression. Nat. Methods 20<\/b>, 1070\u20131081 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Sanjana, N. E., Shalem, O. & Zhang, F. Improved vectors and genome-wide libraries for CRISPR screening. Nat. Methods 11<\/b>, 783\u2013784 (2014).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chylinski, K. et al. CRISPR-switch regulates sgRNA activity by Cre recombination for sequential editing of two loci. Nat. Commun. 10<\/b>, 5454 (2019).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Ramani, B. et al. CRISPR screening by AAV episome-sequencing (CrAAVe-seq) is a highly scalable cell type-specific in vivo screening platform. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2023.06.13.544831<\/a> (2024).<\/p>\n<\/li>\n

  • \n

    Lundin, A. et al. Development of an ObLiGaRe doxycycline inducible Cas9 system for pre-clinical cancer drug discovery. Nat. Commun. 11<\/b>, 4903 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Replogle, J. M. et al. Combinatorial single-cell CRISPR screens by direct guide RNA capture and targeted sequencing. Nat. Biotechnol. 38<\/b>, 954\u2013961 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Xu, Z., Sziraki, A., Lee, J. et al. Dissecting key regulators of transcriptome kinetics through scalable single-cell RNA profiling of pooled CRISPR screens. Nat. Biotechnol. 42<\/b>, 1218\u20131223 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Schraivogel, D., Gschwind, A.R., Milbank, J.H. et al. Targeted Perturb-seq enables genome-scale genetic screens in single cells. Nat. Methods 17<\/b>, 629\u2013635 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Gu, J. et al. Mapping multimodal phenotypes to perturbations in cells and tissue with CRISPRmap. Nat. Biotechnol. 43<\/b>, 1101\u20131115 (2025).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zhang, G. et al. Hydroporation as the mechanism of hydrodynamic delivery. Gene Ther. 11<\/b>, 675\u2013682 (2004).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zhu, S. et al. Guide RNAs with embedded barcodes boost CRISPR-pooled screens. Genome Biol. 20<\/b>, 20 (2019).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Gasperini, M. et al. A genome-wide framework for mapping gene regulation via cellular genetic screens. Cell 176<\/b>, 377\u2013390.e19 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Yao, D. et al. Scalable genetic screening for regulatory circuits using compressed Perturb-seq. Nat. Biotechnol. 42<\/b>, 1282\u20131295 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Huang, A. C. et al. X-Atlas\/Orion: genome-wide Perturb-seq datasets via a scalable fix-cryopreserve platform for training dose-dependent biological foundation models. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2025.06.11.659105<\/a> (2025).<\/p>\n<\/li>\n

  • \n

    Replogle, J. M. et al. Mapping information-rich genotype\u2013phenotype landscapes with genome-scale Perturb-seq. Cell 185<\/b>, 2559\u20132575.e28 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Morgens, D. W. et al. Genome-scale measurement of off-target activity using Cas9 toxicity in high-throughput screens. Nat. Commun. 8<\/b>, 15178 (2017).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Rosenberg, A. B. et al. Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding. Science 360<\/b>, 176\u2013182 (2018).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Almogy, G. et al. Cost-efficient whole genome-sequencing using novel mostly natural sequencing-by-synthesis chemistry and open fluidics platform. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2022.05.29.493900<\/a> (2022).<\/p>\n<\/li>\n

  • \n

    Kim, H. S. et al. CRISPR\/Cas9-mediated gene knockout screens and target identification via whole-genome sequencing uncover host genes required for picornavirus infection. J. Biol. Chem. 292<\/b>, 10664\u201310671 (2017).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lafzi, A., Moutinho, C., Picelli, S. & Heyn, H. Tutorial: guidelines for the experimental design of single-cell RNA sequencing studies. Nat. Protoc. 13<\/b>, 2742\u20132757 (2018).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lee, D. R., Zhang, Y., Rhodes, C. T. & Petros, T. J. Generation of single-cell and single-nuclei suspensions from embryonic and adult mouse brains. Star. Protoc. 4<\/b>, 101944 (2022).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Li, W. et al. MAGeCK enables robust identification of essential genes from genome-scale CRISPR\/Cas9 knockout screens. Genome Biol. 15<\/b>, 554 (2014).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Tian, R. et al. Genome-wide CRISPRi\/a screens in human neurons link lysosomal failure to ferroptosis. Nat. Neurosci. 24<\/b>, 1020\u20131034 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chardon, F. M. et al. Multiplex, single-cell CRISPRa screening for cell type specific regulatory elements. Nat. Commun. 15<\/b>, 8209 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Kampmann, M. CRISPRi and CRISPRa screens in mammalian cells for precision biology and medicine. ACS Chem. Biol. 13<\/b>, 406\u2013416 (2018).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Norman, T. M. et al. Exploring genetic interaction manifolds constructed from rich single-cell phenotypes. Science 365<\/b>, 786\u2013793 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Fulco, C. P. et al. Systematic mapping of functional enhancer\u2013promoter connections with CRISPR interference. Science 354<\/b>, 769\u2013773 (2016).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Hanna, R. E. et al. Massively parallel assessment of human variants with base editor screens. Cell 184<\/b>, 1064\u20131080.e20 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Belli, O., Karava, K., Farouni, R. & Platt, R. J. Multimodal scanning of genetic variants with base and prime editing. Nat. Biotechnol. https:\/\/doi.org\/10.1038\/s41587-024-02439-1<\/a> (2024).<\/p>\n<\/li>\n

  • \n

    Coelho, M. A. et al. Base editing screens define the genetic landscape of cancer drug resistance mechanisms. Nat. Genet. 56<\/b>, 2479\u20132492 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lue, N. Z. & Liau, B. B. Base editor screens for in situ mutational scanning at scale. Mol. Cell 83<\/b>, 2167\u20132187 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Mikuni, T., Nishiyama, J., Sun, Y., Kamasawa, N. & Yasuda, R. High-throughput, high-resolution mapping of protein localization in mammalian brain by in vivo genome editing. Cell 165<\/b>, 1803\u20131817 (2016).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Cho, N. H. et al. OpenCell: endogenous tagging for the cartography of human cellular organization. Science 375<\/b>, eabi6983 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Gautier, A. et al. An engineered protein tag for multiprotein labeling in living cells. Chem. Biol. 15<\/b>, 128\u2013136 (2008).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Sanchez, H. M., Lapidot, T. & Shalem, O. High-throughput optimized prime editing mediated endogenous protein tagging for pooled imaging of protein localization. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2024.09.16.613361<\/a> (2024).<\/p>\n<\/li>\n

  • \n

    Dede, M., McLaughlin, M., Kim, E. & Hart, T. Multiplex enCas12a screens detect functional buffering among paralogs otherwise masked in monogenic Cas9 knockout screens. Genome Biol. 21<\/b>, 262 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Gier, R. A. et al. High-performance CRISPR\u2013Cas12a genome editing for combinatorial genetic screening. Nat. Commun. 11<\/b>, 3455 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Esmaeili Anvar, N. et al. Efficient gene knockout and genetic interaction screening using the in4mer CRISPR\/Cas12a multiplex knockout platform. Nat. Commun. 15<\/b>, 3577 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Campa, C. C., Weisbach, N. R., Santinha, A. J., Incarnato, D. & Platt, R. J. Multiplexed genome engineering by Cas12a and CRISPR arrays encoded on single transcripts. Nat. Methods 16<\/b>, 887\u2013893 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Hsiung, C. C.-S. et al. Engineered CRISPR\u2013Cas12a for higher-order combinatorial chromatin perturbations. Nat. Biotechnol. 43<\/b>, 369\u2013383 (2025).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Bryant, D. H. et al. Deep diversification of an AAV capsid protein by machine learning. Nat. Biotechnol. 39<\/b>, 691\u2013696 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Nonnenmacher, M. et al. Rapid evolution of blood\u2013brain-barrier-penetrating AAV capsids by RNA-driven biopanning. Mol. Ther. Methods Clin. Dev. 20<\/b>, 366\u2013378 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Tabebordbar, M. et al. Directed evolution of a family of AAV capsid variants enabling potent muscle-directed gene delivery across species. Cell 184<\/b>, 4919\u20134938.e22 (2021).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Tsuchida, C. A., Wasko, K. M., Hamilton, J. R. & Doudna, J. A. Targeted nonviral delivery of genome editors in vivo. Proc. Natl Acad. Sci. USA 121<\/b>, e2307796121 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Gleichman, A. J., Kawaguchi, R., Sofroniew, M. V. & Carmichael, S. T. A toolbox of astrocyte-specific, serotype-independent adeno-associated viral vectors using microRNA targeting sequences. Nat. Commun. 14<\/b>, 7426 (2023).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Furlanis, E. et al. An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes. Neuron 113<\/b>, 1525\u20131547.e15 (2025).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Hunker, A. C. et al. Enhancer AAV toolbox for accessing and perturbing striatal cell types and circuits. Neuron 113<\/b>, 1507\u20131524.e17 (2025).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Gosai, S. J. et al. Machine-guided design of cell-type-targeting cis-regulatory elements. Nature 634<\/b>, 1211\u20131220 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    DaSilva, L. F. et al. DNA-diffusion: leveraging generative models for controlling chromatin accessibility and gene expression via synthetic regulatory elements. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2024.02.01.578352<\/a> (2024).<\/p>\n<\/li>\n

  • \n

    Lal, A., Garfield, D., Biancalani, T. & Eraslan, G. Designing realistic regulatory DNA with autoregressive language models. Genome Res. 34<\/b>, 1411\u20131420 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Al-Shayeb, B. et al. Diverse virus-encoded CRISPR\u2013Cas systems include streamlined genome editors. Cell 185<\/b>, 4574\u20134586.e16 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Hino, T. et al. An AsCas12f-based compact genome-editing tool derived by deep mutational scanning and structural analysis. Cell 186<\/b>, 4920\u20134935.e23 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Yan, R. E. et al. Pooled CRISPR screens with joint single-nucleus chromatin accessibility and transcriptome profiling. Nat. Biotechnol. https:\/\/doi.org\/10.1038\/s41587-024-02475-x<\/a> (2024).<\/p>\n<\/li>\n

  • \n

    Tian, F. et al. Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells. Neuron 110<\/b>, 2607\u20132624.e8 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    LaFleur, M. W. & Sharpe, A. H. CRISPR screens to identify regulators of tumor immunity. Annu. Rev. Cancer Biol. 6<\/b>, 103\u2013122 (2022).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Shi, H., Doench, J. G. & Chi, H. CRISPR screens for functional interrogation of immunity. Nat. Rev. Immunol. 23<\/b>, 363\u2013380 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Csendes, G., Sanz, G., Szalay, K. Z. & Szalai, B. Benchmarking foundation cell models for post-perturbation RNA-seq prediction. BMC Genomics 26<\/b>, 393 (2025).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Bunne, C. et al. How to build the virtual cell with artificial intelligence: priorities and opportunities. Cell 187<\/b>, 7045\u20137063 (2024). This perspective brainstorms the use of perturbation datasets to build the artificial intelligence virtual cell.<\/b><\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Rood, J. E., Hupalowska, A. & Regev, A. Toward a foundation model of causal cell and tissue biology with a perturbation cell and tissue atlas. Cell 187<\/b>, 4520\u20134545 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Ahlmann-Eltze, C., Huber, W. & Anders, S. Deep learning-based predictions of gene perturbation effects do not yet outperform simple linear methods. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2024.09.16.613342<\/a> (2024).<\/p>\n<\/li>\n

  • \n

    Lotfollahi, M. et al. Predicting cellular responses to complex perturbations in high\u2010throughput screens. Mol. Syst. Biol. 19<\/b>, e11517 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Bendidi, I. et al. Benchmarking transcriptomics foundation models for perturbation analysis: one PCA still rules them all. Preprint at https:\/\/doi.org\/10.48550\/arXiv.2410.13956<\/a> (2024).<\/p>\n<\/li>\n

  • \n

    Roohani, Y. H. et al. Virtual cell challenge: toward a Turing test for the virtual cell. Cell 188<\/b>, 3370\u20133374 (2025).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zufferey, R., Donello, J. E., Trono, D. & Hope, T. J. Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors. J. Virol. 73<\/b>, 2886\u20132892 (1999).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Barrangou, R. & Horvath, P. A decade of discovery: CRISPR functions and applications. Nat. Microbiol. 2<\/b>, 17092 (2017).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Hille, F. et al. The biology of CRISPR\u2013Cas: backward and forward. Cell 172<\/b>, 1239\u20131259 (2018).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Pacesa, M., Pelea, O. & Jinek, M. Past, present, and future of CRISPR genome editing technologies. Cell 187<\/b>, 1076\u20131100 (2024).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Cong, L. et al. Multiplex genome engineering using CRISPR\/Cas systems. Science 339<\/b>, 819\u2013823 (2013).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Mali, P. et al. RNA-guided human genome engineering via Cas9. Science 339<\/b>, 823\u2013826 (2013).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zetsche, B. et al. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR\u2013Cas system. Cell 163<\/b>, 759\u2013771 (2015).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Fonfara, I., Richter, H., Bratovi\u010d, M., Le Rhun, A. & Charpentier, E. The CRISPR-associated DNA-cleaving enzyme Cpf1 also processes precursor CRISPR RNA. Nature 532<\/b>, 517\u2013521 (2016).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zetsche, B. et al. Multiplex gene editing by CRISPR\u2013Cpf1 using a single crRNA array. Nat. Biotechnol. 35<\/b>, 31\u201334 (2017).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Abudayyeh, O. O. et al. C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector. Science 353<\/b>, aaf5573 (2016).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    East-Seletsky, A. et al. Two distinct RNase activities of CRISPR\u2013C2c2 enable guide-RNA processing and RNA detection. Nature 538<\/b>, 270\u2013273 (2016).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Strecker, J. et al. RNA-guided DNA insertion with CRISPR-associated transposases. Science 365<\/b>, 48\u201353 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Klompe, S. E. et al. Evolutionary and mechanistic diversity of Type I-F CRISPR-associated transposons. Mol. Cell 82<\/b>, 616\u2013628.e5 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    \u00d6zcan, A. et al. Programmable RNA targeting with the single-protein CRISPR effector Cas7-11. Nature 597<\/b>, 720\u2013725 (2021).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Koonin, E. V., Gootenberg, J. S. & Abudayyeh, O. O. Discovery of diverse CRISPR\u2013Cas systems and expansion of the genome engineering toolbox. Biochemistry 62<\/b>, 3465\u20133487 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Gilbert, L. A. et al. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154<\/b>, 442\u2013451 (2013).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Liu, Y. et al. Engineering cell signaling using tunable CRISPR\u2013Cpf1-based transcription factors. Nat. Commun. 8<\/b>, 2095 (2017).<\/p>\n


    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A. & Liu, D. R. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533<\/b>, 420\u2013424 (2016).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Rees, H. A. & Liu, D. R. Base editing: precision chemistry on the genome and transcriptome of living cells. Nat. Rev. Genet. 19<\/b>, 770\u2013788 (2018).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Gaudelli, N. M. et al. Programmable base editing of A\u2022T to G\u2022C in genomic DNA without DNA cleavage. Nature 551<\/b>, 464\u2013471 (2017).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Anzalone, A. V. et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576<\/b>, 149\u2013157 (2019).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chen, P. J. & Liu, D. R. Prime editing for precise and highly versatile genome manipulation. Nat. Rev. Genet. 24<\/b>, 161\u2013177 (2023).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Cox, D. B. T. et al. RNA editing with CRISPR\u2013Cas13. Science 358<\/b>, 1019\u20131027 (2017).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Konermann, S. et al. Transcriptome engineering with RNA-targeting type VI-D CRISPR effectors. Cell 173<\/b>, 665\u2013676.e14 (2018).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Charles, E. J. et al. Engineering improved Cas13 effectors for targeted post-transcriptional regulation of gene expression. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2021.05.26.445687<\/a> (2021).<\/p>\n<\/li>\n

  • \n

    Otoupal, P. B., Cress, B. F., Doudna, J. A. & Schoeniger, J. S. CRISPR-RNAa: targeted activation of translation using dCas13 fusions to translation initiation factors. Nucleic Acids Res. 50<\/b>, 8986\u20138998 (2022).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Makarova, K. S. et al. Evolutionary classification of CRISPR\u2013Cas systems: a burst of class 2 and derived variants. Nat. Rev. Microbiol. 18<\/b>, 67\u201383 (2020).<\/p>\n

    CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n","protected":false},"excerpt":{"rendered":"Auton, A. et al. A global reference for human genetic variation. Nature 526, 68\u201374 (2015). Google Scholar\u00a0 Garc\u00eda-Garc\u00eda,…\n","protected":false},"author":3,"featured_media":101955,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[26],"tags":[2906,21939,15576,6958,66328,66329,21938,834,815,66330,15577,159,66331,67,132,68],"class_list":{"0":"post-101954","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-agriculture","9":"tag-animal-genetics-and-genomics","10":"tag-biomedicine","11":"tag-cancer-research","12":"tag-crispr-cas-systems","13":"tag-functional-genomics","14":"tag-gene-function","15":"tag-general","16":"tag-genetics","17":"tag-high-throughput-screening","18":"tag-human-genetics","19":"tag-science","20":"tag-transcriptomics","21":"tag-united-states","22":"tag-unitedstates","23":"tag-us"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@us\/114936321301842935","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/101954","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/comments?post=101954"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/101954\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media\/101955"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media?parent=101954"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/categories?post=101954"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/tags?post=101954"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}