Applications of CRISPR genome editing technology in drug target identification and validation

References

• Plenge RM. Disciplined approach to drug discovery and early development. Sci Transl Med. 2016;8(349):349ps15.
   PubMed Web of Science ®Google Scholar
• Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921.
   PubMed Web of Science ®Google Scholar
• ENCODE. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489:57–74.
   PubMed Web of Science ®Google Scholar
• Patel DV, Gordon EM. Applications of small molecule combinatorial chemistry to Drug Discovery. Drug Discovery Today. 1996;1(4):134–144.
   Google Scholar
• Macarron R, Banks MN, Bojanic D, et al. Impact of high-throughput screening in biomedical research. Nat Rev Drug Discov. 2011;10:188–195.
   PubMed Web of Science ®Google Scholar
• Jorgensen WL. The many roles of computation in drug discovery. Science. 2004;303:1813–1818.
   PubMed Web of Science ®Google Scholar
• Hannon GJ. RNA interference. Nature. 2002;418:244–251.
   PubMed Web of Science ®Google Scholar
• Scannell JW, Blanckley A, Boldon H, et al. Diagnosing the decline in pharmaceutical R&D efficiency. Nat Rev Drug Discov. 2012;11:191–200.
   PubMed Web of Science ®Google Scholar
• DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016;47:20–33.
   PubMed Web of Science ®Google Scholar
• Eder J, Sedrani R, Wiesmann C. The discovery of first-in-class drugs: origins and evolution. Nat Rev Drug Discov. 2014;13:577–587.
   PubMed Web of Science ®Google Scholar
• Scannell JW, Bosley J. When quality beats quantity: decision theory, drug discovery, and the reproducibility crisis. Plos One. 2016;11:e0147215.
   PubMed Web of Science ®Google Scholar
• Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell. 2014;157:1262–1278.
   PubMed Web of Science ®Google Scholar
• Jinek M, Chylinski K, Fonfara I, et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 2012;337:816–821.
   PubMed Web of Science ®Google Scholar
• Chakraborty S, Ji H, Kabadi AM, et al. A CRISPR/Cas9-based system for reprogramming cell lineage specification. Stem Cell Reports. 2014;3:940–947.
   PubMed Web of Science ®Google Scholar
• Chen B, Gilbert LA, Cimini BA, et al. Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell. 2013;155:1479–1491.
   PubMed Web of Science ®Google Scholar
• Tanenbaum ME, Gilbert LA, Qi LS, et al. A protein-tagging system for signal amplification in gene expression and fluorescence imaging. Cell. 2014;159:635–646.
   PubMed Web of Science ®Google Scholar
• Ma H, Naseri A, Reyes-Gutierrez P, et al. Multicolor CRISPR labeling of chromosomal loci in human cells. Proc Natl Acad Sci U S A. 2015;112:3002–3007.
   PubMed Web of Science ®Google Scholar
• Ma H, Tu LC, Naseri A, et al. Multiplexed labeling of genomic loci with dCas9 and engineered sgRNAs using CRISPRainbow. Nat Biotechnol. 2016;34:528–531.
   PubMed Web of Science ®Google Scholar
• Hilton IB, D’Ippolito AM, Vockley CM, et al. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nat Biotechnol. 2015;33:510–517.
   PubMed Web of Science ®Google Scholar
• Kearns NA, Pham H, Tabak B, et al. Functional annotation of native enhancers with a Cas9-histone demethylase fusion. Nat Methods. 2015;12:401–403.
   PubMed Web of Science ®Google Scholar
• Dominguez AA, Lim WA, Qi LS. Beyond editing: repurposing CRISPR-Cas9 for precision genome regulation and interrogation. Nat Rev Mol Cell Biol. 2016;17:5–15.
   PubMed Web of Science ®Google Scholar
• Tycko J, Myer VE, Hsu PD. Methods for optimizing CRISPR-Cas9 genome editing specificity. Mol Cell. 2016;63:355–370.
   PubMed Web of Science ®Google Scholar
• Ran FA, Hsu PD, Lin CY, et al. Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell. 2013;154:1380–1389.
   PubMed Web of Science ®Google Scholar
• Slaymaker IM, Gao L, Zetsche B, et al. Rationally engineered Cas9 nucleases with improved specificity. Science. 2016;351:84–88.
   PubMed Web of Science ®Google Scholar
• Kleinstiver BP, Pattanayak V, Prew MS, et al. High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature. 2016;529:490–495.
   PubMed Web of Science ®Google Scholar
• Kleinstiver BP, Prew MS, Tsai SQ, et al. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature. 2015;523:481–485.
   PubMed Web of Science ®Google Scholar
• Zetsche B, Gootenberg JS, Abudayyeh OO, et al. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell. 2015;163:759–771.
   PubMed Web of Science ®Google Scholar
• Friedland AE, Tzur YB, Esvelt KM, et al. Heritable genome editing in C. elegans via a CRISPR-Cas9 system. Nat Methods. 2013;10:741–743.
   PubMed Web of Science ®Google Scholar
• Muller M, Lee CM, Gasiunas G, et al. Streptococcus thermophilus CRISPR-Cas9 systems enable specific editing of the human genome. Mol Ther. 2016;24:636–644.
   PubMed Web of Science ®Google Scholar
• Mali P, Aach J, Stranges PB, et al. CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat Biotechnol. 2013;31:833–838.
   PubMed Web of Science ®Google Scholar
• Perez-Pinera P, Kocak DD, Vockley CM, et al. RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat Methods. 2013;10:973–976.
   PubMed Web of Science ®Google Scholar
• Maeder ML, Linder SJ, Cascio VM, et al. CRISPR RNA-guided activation of endogenous human genes. Nat Methods. 2013;10:977–979.
   PubMed Web of Science ®Google Scholar
• Konermann S, Brigham MD, Trevino AE, et al. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature. 2015;517:583–588.
   PubMed Web of Science ®Google Scholar
• Miyaoka Y, Berman JR, Cooper SB, et al. Systematic quantification of HDR and NHEJ reveals effects of locus, nuclease, and cell type on genome-editing. Sci Rep. 2016;6:23549.
   PubMed Web of Science ®Google Scholar
• Sakuma T, Nishikawa A, Kume S, et al. Multiplex genome engineering in human cells using all-in-one CRISPR/Cas9 vector system. Sci Rep. 2014;4:5400.
   PubMed Web of Science ®Google Scholar
• Liang X, Potter J, Kumar S, et al. Rapid and highly efficient mammalian cell engineering via Cas9 protein transfection. J Biotechnol. 2015;208:44–53.
   PubMed Web of Science ®Google Scholar
• Steyer B, Carlson-Stevermer J, Angenent-Mari N, et al. High content analysis platform for optimization of lipid mediated CRISPR-Cas9 delivery strategies in human cells. Acta Biomater. 2016;34:143–158.
   PubMed Web of Science ®Google Scholar
• Kim S, Kim D, Cho SW, et al. Highly efficient RNA-guided genome editing in human cells via delivery of purified Cas9 ribonucleoproteins. Genome Res. 2014;24:1012–1019.
   PubMed Web of Science ®Google Scholar
• Schumann K, Lin S, Boyer E, et al. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins. Proc Natl Acad Sci U S A. 2015;112:10437–10442.
   PubMed Web of Science ®Google Scholar
• Yu X, Liang X, Xie H, et al. Improved delivery of Cas9 protein/gRNA complexes using lipofectamine CRISPRMAX. Biotechnol Lett. 2016;38:919–929.
   PubMed Web of Science ®Google Scholar
• Zuris JA, Thompson DB, Shu Y, et al. Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo. Nat Biotechnol. 2015;33:73–80.
   PubMed Web of Science ®Google Scholar
• Wang M, Zuris JA, Meng F, et al. Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles. Proc Natl Acad Sci U S A. 2016;113:2868–2873.
   PubMed Web of Science ®Google Scholar
• Clontech. Efficient delivery of active Cas9 protein and target-specific sgRNA to a broad range of cell types, 2016. Available from: http://www.clontech.com/US/Products/Genome_Editing/CRISPR_Cas9/Technical_Notes/CRISPR_Cas9_Gesicles_Cell_Types.
   Google Scholar
• Marx V. Gene editing: how to stay on-target with CRISPR. Nat Methods. 2014;11(10):1021–1026.
   Google Scholar
• Qiu P, Shandilya H, D’Alessio JM, et al. Mutation detection using Surveyor nuclease. Biotechniques. 2004;36:702–707.
   PubMed Web of Science ®Google Scholar
• Brinkman EK, Chen T, Amendola M. van SB. Easy quantitative assessment of genome editing by sequence trace decomposition. Nucleic Acids Res. 2014;42:e168.
   PubMed Web of Science ®Google Scholar
• Schmid-Burgk JL, Schmidt T, Gaidt MM, et al. OutKnocker: a web tool for rapid and simple genotyping of designer nuclease edited cell lines. Genome Res. 2014;24:1719–1723.
   PubMed Web of Science ®Google Scholar
• De Vree PJ, De WE, Yilmaz M, et al. Targeted sequencing by proximity ligation for comprehensive variant detection and local haplotyping. Nat Biotechnol. 2014;32:1019–1025.
   PubMed Web of Science ®Google Scholar
• Tsai SQ, Zheng Z, Nguyen NT, et al. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat Biotechnol. 2015;33:187–197.
   PubMed Web of Science ®Google Scholar
• Kim D, Bae S, Park J, et al. Digenome-seq: genome-wide profiling of CRISPR-Cas9 off-target effects in human cells. Nat Methods. 2015;12(237–43):1.
   PubMedGoogle Scholar
• Crosetto N, Mitra A, Silva MJ, et al. Nucleotide-resolution DNA double-strand break mapping by next-generation sequencing. Nat Methods. 2013;10:361–365.
   PubMed Web of Science ®Google Scholar
• Shalem O, Sanjana NE, Hartenian E, et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science. 2014;343:84–87.
   PubMed Web of Science ®Google Scholar
• Leung AW. de ST, Bally MB, Lockwood WW. Synthetic lethality in lung cancer and translation to clinical therapies. Mol Cancer. 2016;15:61.
   PubMed Web of Science ®Google Scholar
• Kiessling MK, Schuierer S, Stertz S, et al. Identification of oncogenic driver mutations by genome-wide CRISPR-Cas9 dropout screening. BMC Genomics. 2016;17:723.
   PubMed Web of Science ®Google Scholar
• Wang T, Birsoy K, Hughes NW, et al. Identification and characterization of essential genes in the human genome. Science. 2015;350:1096–1101.
   PubMed Web of Science ®Google Scholar
• Wong AS, Choi GC, Cui CH, et al. Multiplexed barcoded CRISPR-Cas9 screening enabled by CombiGEM. Proc Natl Acad Sci U S A. 2016;113:2544–2549.
   PubMed Web of Science ®Google Scholar
• Wang T, Wei JJ, Sabatini DM, et al. Genetic screens in human cells using the CRISPR-Cas9 system. Science. 2014;343:80–84.
   PubMed Web of Science ®Google Scholar
• Koike-Yusa H, Li Y, Tan EP, et al. Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library. Nat Biotechnol. 2014;32:267–273.
   PubMed Web of Science ®Google Scholar
• Shi J, Wang E, Milazzo JP, et al. Discovery of cancer drug targets by CRISPR-Cas9 screening of protein domains. Nat Biotechnol. 2015;33:661–667.
   PubMed Web of Science ®Google Scholar
• Canver MC, Smith EC, Sher F, et al. BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis. Nature. 2015;527:192–197.
   PubMed Web of Science ®Google Scholar
• Korkmaz G, Lopes R, Ugalde AP, et al. Functional genetic screens for enhancer elements in the human genome using CRISPR-Cas9. Nat Biotechnol. 2016;34:192–198.
   PubMed Web of Science ®Google Scholar
• Diao Y, Li B, Meng Z, et al. A new class of temporarily phenotypic enhancers identified by CRISPR/Cas9-mediated genetic screening. Genome Res. 2016;26:397–405.
   PubMed Web of Science ®Google Scholar
• Ho TT, Zhou N, Huang J, et al. Targeting non-coding RNAs with the CRISPR/Cas9 system in human cell lines. Nucleic Acids Res. 2015;43:e17.
   PubMed Web of Science ®Google Scholar
• Li J, Shou J, Guo Y, et al. Efficient inversions and duplications of mammalian regulatory DNA elements and gene clusters by CRISPR/Cas9. J Mol Cell Biol. 2015;7:284–298.
   PubMed Web of Science ®Google Scholar
• Choi PS, Meyerson M. Targeted genomic rearrangements using CRISPR/Cas technology. Nat Commun. 2014;5:3728.
   PubMed Web of Science ®Google Scholar
• Claussnitzer M, Dankel SN, Kim KH, et al. FTO Obesity Variant Circuitry and Adipocyte Browning in Humans. N Engl J Med. 2015;373:895–907.
   PubMed Web of Science ®Google Scholar
• Smith C, Abalde-Atristain L, He C, et al. Efficient and allele-specific genome editing of disease loci in human iPSCs. Mol Ther. 2015;23:570–577.
   PubMed Web of Science ®Google Scholar
• Paquet D, Kwart D, Chen A, et al. Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9. Nature. 2016;533:125–129.
   PubMed Web of Science ®Google Scholar
• Kasap C, Elemento O, Kapoor TM. DrugTargetSeqR: a genomics- and CRISPR-Cas9-based method to analyze drug targets. Nat Chem Biol. 2014;10:626–628.
   PubMed Web of Science ®Google Scholar
• Neggers JE, Vercruysse T, Jacquemyn M, et al. Identifying drug-target selectivity of small-molecule CRM1/XPO1 inhibitors by CRISPR/Cas9 genome editing. Chem Biol. 2015;22:107–116.
   PubMedGoogle Scholar
• Smurnyy Y, Cai M, Wu H, et al. DNA sequencing and CRISPR-Cas9 gene editing for target validation in mammalian cells. Nat Chem Biol. 2014;10:623–625.
   PubMed Web of Science ®Google Scholar
• Findlay GM, Boyle EA, Hause RJ, et al. Saturation editing of genomic regions by multiplex homology-directed repair. Nature. 2014;513:120–123.
   PubMed Web of Science ®Google Scholar
• Singh AK, Carette X, Potluri LP, et al. Investigating essential gene function in Mycobacterium tuberculosis using an efficient CRISPR interference system. Nucleic Acids Res. 2016;44:e143.
   PubMed Web of Science ®Google Scholar
• Mandegar MA, Huebsch N, Frolov EB, et al. CRISPR Interference efficiently induces specific and reversible gene silencing in human iPSCs. Cell Stem Cell. 2016;18(4):541–553.
   PubMed Web of Science ®Google Scholar
• Gilbert LA, Larson MH, Morsut L, et al. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell. 2013;154:442–451.
   PubMed Web of Science ®Google Scholar
• Cheng AW, Wang H, Yang H, et al. Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system. Cell Res. 2013;23:1163–1171.
   PubMed Web of Science ®Google Scholar
• Vojta A, Dobrinic P, Tadic V, et al. Repurposing the CRISPR-Cas9 system for targeted DNA methylation. Nucleic Acids Res. 2016;44(12):5615–5628.
   PubMed Web of Science ®Google Scholar
• Liszczak GP, Brown ZZ, Kim SH, et al. Genomic targeting of epigenetic probes using a chemically tailored Cas9 system. Proc Natl Acad Sci U S A. 2017;114:681–686.
   PubMed Web of Science ®Google Scholar
• Zalatan JG, Lee ME, Almeida R, et al. Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds. Cell. 2015;160:339–350.
   PubMed Web of Science ®Google Scholar
• Nelles DA, Fang MY, O’Connell MR, et al. Programmable RNA Tracking in Live Cells with CRISPR/Cas9. Cell. 2016;165:488–496.
   PubMed Web of Science ®Google Scholar
• Oakes BL, Nadler DC, Flamholz A, et al. Profiling of engineering hotspots identifies an allosteric CRISPR-Cas9 switch. Nat Biotechnol. 2016;34(6):646–651.
   PubMed Web of Science ®Google Scholar
• Gonzalez F, Zhu Z, Shi ZD, et al. An iCRISPR platform for rapid, multiplexable, and inducible genome editing in human pluripotent stem cells. Cell Stem Cell. 2014;15:215–226.
   PubMed Web of Science ®Google Scholar
• Agrotis A, Ketteler R. A new age in functional genomics using CRISPR/Cas9 in arrayed library screening. Front Genet. 2015;6:300.
   PubMed Web of Science ®Google Scholar
• Schmidt T, Schmid-Burgk JL, Hornung V. Synthesis of an arrayed sgRNA library targeting the human genome. Sci Rep. 2015;5:14987.
   PubMed Web of Science ®Google Scholar
• Chen S, Sanjana NE, Zheng K, et al. Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis. Cell. 2015;160:1246–1260.
   PubMed Web of Science ®Google Scholar
• Gilbert LA, Horlbeck MA, Adamson B, et al. Genome-scale CRISPR-Mediated control of gene repression and activation. Cell. 2014;159:647–661.
   PubMed Web of Science ®Google Scholar
• Toledo CM, Ding Y, Hoellerbauer P, et al. Genome-wide CRISPR-Cas9 screens reveal loss of redundancy between PKMYT1 and WEE1 in Glioblastoma stem-like cells. Cell Rep. 2015;13:2425–2439.
   PubMed Web of Science ®Google Scholar
• Project Achilles, the Broad institute of MIT and Harvard. Available from: https://portals.broadinstitute.org/achilles
   Google Scholar
• Cowley GS, Weir BA, Vazquez F, et al. Parallel genome-scale loss of function screens in 216 cancer cell lines for the identification of context-specific genetic dependencies. Sci Data. 2014;1:140035.
   PubMed Web of Science ®Google Scholar
• Zuber J, McJunkin K, Fellmann C, et al. Toolkit for evaluating genes required for proliferation and survival using tetracycline-regulated RNAi. Nat Biotechnol. 2011;29:79–83.
   PubMed Web of Science ®Google Scholar
• Singh S, Wu X, Ljosa V, et al. Morphological Profiles of RNAi-Induced gene knockdown are highly reproducible but dominated by seed effects. Plos One. 2015;10:e0131370.
   Web of Science ®Google Scholar
• Echeverri CJ, Beachy PA, Baum B, et al. Minimizing the risk of reporting false positives in large-scale RNAi screens. Nat Methods. 2006;3:777–779.
   PubMed Web of Science ®Google Scholar
• Deans RM, Morgens DW, Okesli A, et al. Parallel shRNA and CRISPR-Cas9 screens enable antiviral drug target identification. Nat Chem Biol. 2016;12(5):361–366.
   PubMed Web of Science ®Google Scholar
• Evers B, Jastrzebski K, Heijmans JP, et al. CRISPR knockout screening outperforms shRNA and CRISPRi in identifying essential genes. Nat Biotechnol. 2016;34(6):631-633.
   PubMed Web of Science ®Google Scholar
• Morgens DW, Deans RM, Li A, et al. Systematic comparison of CRISPR/Cas9 and RNAi screens for essential genes. Nat Biotechnol. 2016;34:634–636.
   PubMed Web of Science ®Google Scholar
• Munoz DM. CRISPR screens provide a comprehensive assessment of cancer vulnerabilities but generate false-positive hits for highly amplified genomic regions. Cancer Discov. 2016;6(8):900–913.
   Google Scholar
• Aguirre AJ, Meyers RM, Weir BA, et al. Genomic copy number dictates a gene-independent cell response to CRISPR/Cas9 targeting. Cancer Discov. 2016;6:914–929.
   PubMed Web of Science ®Google Scholar
• Wanzel M, Vischedyk JB, Gittler MP, et al. CRISPR-Cas9-based target validation for p53-reactivating model compounds. Nat Chem Biol. 2016;12:22–28.
   PubMed Web of Science ®Google Scholar
• Arrowsmith CH, Audia JE, Austin C, et al. The promise and peril of chemical probes. Nat Chem Biol. 2015;11:536–541.
   PubMed Web of Science ®Google Scholar
• Munoz L. Non-kinase targets of protein kinase inhibitors. Nat Rev Drug Discov. 2017 Mar 10. doi: 10.1038/nrd.2016.266. [Epub ahead of print].
   PubMedGoogle Scholar
• Altshuler D, Daly MJ, Lander ES. Genetic mapping in human disease. Science. 2008;322:881–888.
   PubMed Web of Science ®Google Scholar
• Farnier M. PCSK9: from discovery to therapeutic applications. Arch Cardiovasc Dis. 2014;107:58–66.
   PubMed Web of Science ®Google Scholar
• Edwards SL, Beesley J, French JD, et al. Beyond GWASs: illuminating the dark road from association to function. Am J Hum Genet. 2013;93:779–797.
   PubMed Web of Science ®Google Scholar
• Maurano MT, Humbert R, Rynes E, et al. Systematic localization of common disease-associated variation in regulatory DNA. Science. 2012;337:1190–1195.
   PubMed Web of Science ®Google Scholar
• Maurano MT, Haugen E, Sandstrom R, et al. Large-scale identification of sequence variants influencing human transcription factor occupancy in vivo. Nat Genet. 2015;47:1393–1401.
   PubMed Web of Science ®Google Scholar
• Ma D, Liu F. Genome editing and its applications in model organisms. Genomics Proteomics Bioinformatics. 2015;13:336–344.
   PubMed Web of Science ®Google Scholar
• Spisak S, Lawrenson K, Fu Y, et al. CAUSEL: an epigenome- and genome-editing pipeline for establishing function of noncoding GWAS variants. Nat Med. 2015;21:1357–1363.
   PubMed Web of Science ®Google Scholar
• Rajagopal N, Srinivasan S, Kooshesh K, et al. High-throughput mapping of regulatory DNA. Nat Biotechnol. 2016;34:167–174.
   PubMed Web of Science ®Google Scholar
• Freedman BS, Brooks CR, Lam AQ, et al. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nat Commun. 2015;6:8715.
   PubMed Web of Science ®Google Scholar
• Firth AL, Menon T, Parker GS, et al. Functional gene correction for cystic fibrosis in lung epithelial cells generated from patient iPSCs. Cell Rep. 2015;12:1385–1390.
   PubMed Web of Science ®Google Scholar
• Lagutina IV, Valentine V, Picchione F, et al. Modeling of the human alveolar rhabdomyosarcoma Pax3-Foxo1 chromosome translocation in mouse myoblasts using CRISPR-Cas9 nuclease. Plos Genet. 2015;11:e1004951.
   PubMed Web of Science ®Google Scholar
• Banno K, Omori S, Hirata K, et al. Systematic cellular disease models reveal synergistic interaction of trisomy 21 and GATA1 Mutations in hematopoietic abnormalities. Cell Rep. 2016;15:1228–1241.
   PubMed Web of Science ®Google Scholar
• Merkle FT, Eggan K. Modeling human disease with pluripotent stem cells: from genome association to function. Cell Stem Cell. 2013;12:656–668.
   PubMed Web of Science ®Google Scholar
• Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316:889–894.
   PubMed Web of Science ®Google Scholar
• Smemo S, Tena JJ, Kim KH, et al. Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature. 2014;507:371–375.
   PubMed Web of Science ®Google Scholar
• Wang H, Yang H, Shivalila CS, et al. One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell. 2013;153:910–918.
   PubMed Web of Science ®Google Scholar
• Li D, Qiu Z, Shao Y, et al. Heritable gene targeting in the mouse and rat using a CRISPR-Cas system. Nat Biotechnol. 2013;31:681–683.
   PubMed Web of Science ®Google Scholar
• Li W, Teng F, Li T, et al. Simultaneous generation and germline transmission of multiple gene mutations in rat using CRISPR-Cas systems. Nat Biotechnol. 2013;31:684–686.
   PubMed Web of Science ®Google Scholar
• Long C, McAnally JR, Shelton JM, et al. Prevention of muscular dystrophy in mice by CRISPR/Cas9-mediated editing of germline DNA. Science. 2014;345:1184–1188.
   PubMed Web of Science ®Google Scholar
• Hu X, Chang N, Wang X, et al. Heritable gene-targeting with gRNA/Cas9 in rats. Cell Res. 2013;23:1322–1325.
   PubMed Web of Science ®Google Scholar
• Ma Y, Shen B, Zhang X, et al. Heritable multiplex genetic engineering in rats using CRISPR/Cas9. Plos One. 2014;9:e89413.
   PubMed Web of Science ®Google Scholar
• Yoshimi K, Kaneko T, Voigt B, et al. Allele-specific genome editing and correction of disease-associated phenotypes in rats using the CRISPR-Cas platform. Nat Commun. 2014;5:4240.
   PubMed Web of Science ®Google Scholar
• Wu Y, Liang D, Wang Y, et al. Correction of a genetic disease in mouse via use of CRISPR-Cas9. Cell Stem Cell. 2013;13:659–662.
   PubMed Web of Science ®Google Scholar
• Grone BP, Marchese M, Hamling KR, et al. Epilepsy, behavioral abnormalities, and physiological comorbidities in syntaxin-binding protein 1 (STXBP1) Mutant Zebrafish. Plos One. 2016;11:e0151148.
   PubMed Web of Science ®Google Scholar
• Hofsteen P, Robitaille AM, Chapman DP, et al. Quantitative proteomics identify DAB2 as a cardiac developmental regulator that inhibits WNT/beta-catenin signaling. Proc Natl Acad Sci U S A. 2016;113:1002–1007.
   PubMed Web of Science ®Google Scholar
• Pannicke T, Frommherz I, Biedermann B, et al. Differential effects of P2Y1 deletion on glial activation and survival of photoreceptors and amacrine cells in the ischemic mouse retina. Cell Death Dis. 2014;5:e1353.
   PubMed Web of Science ®Google Scholar
• Ablain J, Durand EM, Yang S, et al. A CRISPR/Cas9 vector system for tissue-specific gene disruption in zebrafish. Dev Cell. 2015;32:756–764.
   PubMed Web of Science ®Google Scholar
• Nakamura K, Fujii W, Tsuboi M, et al. Generation of muscular dystrophy model rats with a CRISPR/Cas system. Sci Rep. 2014;4:5635.
   PubMed Web of Science ®Google Scholar
• Heckl D, Kowalczyk MS, Yudovich D, et al. Generation of mouse models of myeloid malignancy with combinatorial genetic lesions using CRISPR-Cas9 genome editing. Nat Biotechnol. 2014;32:941–946.
   PubMed Web of Science ®Google Scholar
• Xue W, Chen S, Yin H, et al. CRISPR-mediated direct mutation of cancer genes in the mouse liver. Nature. 2014;514:380–384.
   PubMed Web of Science ®Google Scholar
• Niu Y, Shen B, Cui Y, et al. Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos. Cell. 2014;156:836–843.
   PubMed Web of Science ®Google Scholar
• Kang Y, Zheng B, Shen B, et al. CRISPR/Cas9-mediated Dax1 knockout in the monkey recapitulates human AHC-HH. Hum Mol Genet. 2015;24:7255–7264.
   PubMed Web of Science ®Google Scholar
• Wan H, Feng C, Teng F, et al. One-step generation of p53 gene biallelic mutant Cynomolgus monkey via the CRISPR/Cas system. Cell Res. 2015;25:258–261.
   PubMed Web of Science ®Google Scholar
• Chen Y, Zheng Y, Kang Y, et al. Functional disruption of the dystrophin gene in rhesus monkey using CRISPR/Cas9. Hum Mol Genet. 2015;24:3764–3774.
   PubMed Web of Science ®Google Scholar
• Chen Y, Niu Y, Ji W. Genome editing in nonhuman primates: approach to generating human disease models. J Intern Med. 2016;280(3):246–251.
   PubMed Web of Science ®Google Scholar
• Carlson-Stevermer J, Goedland M, Steyer B, et al. High-content analysis of CRISPR-Cas9 Gene-edited human embryonic stem cells. Stem Cell Reports. 2016;6:109–120.
   PubMed Web of Science ®Google Scholar
• Nie J, Hashino E. Organoid technologies meet genome engineering. EMBO Rep. 2017;18:367–376.
   PubMed Web of Science ®Google Scholar
• Richardson CD, Ray GJ, DeWitt MA, et al. Enhancing homology-directed genome editing by catalytically active and inactive CRISPR-Cas9 using asymmetric donor DNA. Nat Biotechnol. 2016;34:339–344.
   PubMed Web of Science ®Google Scholar
• Lin S, Staahl BT, Alla RK, et al. Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery. Elife. 2014;3:e04766.
   PubMed Web of Science ®Google Scholar
• Yu C, Liu Y, Ma T, et al. Small molecules enhance CRISPR genome editing in pluripotent stem cells. Cell Stem Cell. 2015;16:142–147.
   PubMed Web of Science ®Google Scholar
• Bhatia SN, Ingber DE. Microfluidic organs-on-chips. Nat Biotechnol. 2014;32:760–772.
   PubMed Web of Science ®Google Scholar
• Reardon S. ‘Organs-on-chips’ go mainstream. Nature. 2015;523:266.
   PubMed Web of Science ®Google Scholar
• Sterneckert JL, Reinhardt P, Scholer HR. Investigating human disease using stem cell models. Nat Rev Genet. 2014;15:625–639.
   PubMed Web of Science ®Google Scholar