{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:19:48Z","timestamp":1790835588056,"version":"4.1.0"},"reference-count":112,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T00:00:00Z","timestamp":1547510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T00:00:00Z","timestamp":1547510400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T00:00:00Z","timestamp":1547510400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI109532"],"award-info":[{"award-number":["R21AI109532"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["PHD\/0011\/2555"],"award-info":[{"award-number":["PHD\/0011\/2555"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["PHD\/0047\/2556"],"award-info":[{"award-number":["PHD\/0047\/2556"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["PHD\/00531\/2556"],"award-info":[{"award-number":["PHD\/00531\/2556"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["107475\/Z\/15\/Z"],"award-info":[{"award-number":["107475\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["WT 098051"],"award-info":[{"award-number":["WT 098051"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MaxMind Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>CRISPR\/Cas9-based genome editing has yet to be reported in species of the Platyhelminthes. We tested this approach by targeting omega-1 (\u03c91) of Schistosoma mansoni as proof of principle. This secreted ribonuclease is crucial for Th2 polarization and granuloma formation. Schistosome eggs were exposed to Cas9 complexed with guide RNA complementary to \u03c91 by electroporation or by transduction with lentiviral particles. Some eggs were also transfected with a single stranded donor template. Sequences of amplicons from gene-edited parasites exhibited Cas9-catalyzed mutations including homology directed repaired alleles, and other analyses revealed depletion of \u03c91 transcripts and the ribonuclease. Gene-edited eggs failed to polarize Th2 cytokine responses in macrophage\/T-cell co-cultures, while the volume of pulmonary granulomas surrounding \u03c91-mutated eggs following tail-vein injection into mice was vastly reduced. Knock-out of \u03c91 and the diminished levels of these cytokines following exposure showcase the novel application of programmed gene editing for functional genomics in schistosomes.<\/jats:p>","DOI":"10.7554\/elife.41337","type":"journal-article","created":{"date-parts":[[2019,1,14]],"date-time":"2019-01-14T19:03:32Z","timestamp":1547492612000},"source":"Crossref","is-referenced-by-count":99,"title":["Programmed genome editing of the omega-1 ribonuclease of the blood fluke, Schistosoma mansoni"],"prefix":"10.7554","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9411-8883","authenticated-orcid":true,"given":"Wannaporn","family":"Ittiprasert","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, United States"},{"name":"Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria H","family":"Mann","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, United States"},{"name":"Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2079-0973","authenticated-orcid":true,"given":"Shannon E","family":"Karinshak","sequence":"additional","affiliation":[{"name":"Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avril","family":"Coghlan","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geetha","family":"Sankaranarayanan","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apisit","family":"Chaidee","sequence":"additional","affiliation":[{"name":"Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC, United States"},{"name":"Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Tanno","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Maryland, Baltimore, United States"},{"name":"Institute of Human Virology, University of Maryland, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chutima","family":"Kumkhaek","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Therapeutics Laboratory, National Heart, Lungs and Blood Institute, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pannathee","family":"Prangtaworn","sequence":"additional","affiliation":[{"name":"Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC, United States"},{"name":"Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret M","family":"Mentink-Kane","sequence":"additional","affiliation":[{"name":"Schistosomiasis Resource Center, Biomedical Research Institute, Rockville, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina J","family":"Cochran","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Driguez","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Holroyd","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Tracey","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rutchanee","family":"Rodpai","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Everts","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis H","family":"Hokke","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl F","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9581-0377","authenticated-orcid":true,"given":"Matthew","family":"Berriman","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1765-0002","authenticated-orcid":true,"given":"Paul J","family":"Brindley","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2019,1,15]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1101\/386219","article-title":"Programmed knockout mutation of liverfluke granulin attenuates virulence of infection-induced hepatobiliary morbidity","volume":"8","author":"Arunsan","year":"2019","journal-title":"Biorxiv"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1017\/S0031182001007351","article-title":"The schistosome egg: development and secretions","volume":"122","author":"Ashton","year":"2001","journal-title":"Parasitology"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1038\/nature08160","article-title":"The genome of the blood fluke Schistosoma mansoni","volume":"460","author":"Berriman","year":"2009","journal-title":"Nature"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1084\/jem.132.3.488","article-title":"Delayed hypersensitivity-type granuloma formation and dermal reaction induced and elicited by a soluble factor isolated from Schistosoma mansoni eggs","volume":"132","author":"Boros","year":"1970","journal-title":"Journal of Experimental Medicine"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Analytical Biochemistry"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1038\/nprot.2018.005","article-title":"Integrated design, execution, and analysis of arrayed and pooled CRISPR genome-editing experiments","volume":"13","author":"Canver","year":"2018","journal-title":"Nature Protocols"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1475-2859-6-1","article-title":"Polymyxin B as inhibitor of LPS contamination of Schistosoma mansoni recombinant proteins in human cytokine analysis","volume":"6","author":"Cardoso","year":"2007","journal-title":"Microbial Cell Factories"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.molbiopara.2007.06.002","article-title":"Proteomic analysis of Schistosoma mansoni egg secretions","volume":"155","author":"Cass","year":"2007","journal-title":"Molecular and Biochemical Parasitology"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"3008","DOI":"10.1038\/s41467-018-05425-9","article-title":"Targeted delivery of CRISPR-Cas9 ribonucleoprotein into arthropod ovaries for heritable germline gene editing","volume":"9","author":"Chaverra-Rodriguez","year":"2018","journal-title":"Nature Communications"},{"key":"bib10","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.4049\/jimmunol.148.10.3244","article-title":"Treatment with anti-IL-2 antibodies reduces hepatic pathology and eosinophilia in Schistosoma mansoni-infected mice while selectively inhibiting T cell IL-5 production","volume":"148","author":"Cheever","year":"1992","journal-title":"Journal of Immunology"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/978-1-4939-1862-1_14","article-title":"Gene editing using ssODNs with engineered endonucleases","volume":"1239","author":"Chen","year":"2015","journal-title":"Methods in Molecular Biology"},{"key":"bib12","first-page":"532","article-title":"A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples","volume":"15","author":"Chomczynski","year":"1993","journal-title":"BioTechniques"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"2253","DOI":"10.1016\/S0140-6736(13)61949-2","article-title":"Human schistosomiasis","volume":"383","author":"Colley","year":"2014","journal-title":"The Lancet"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"S25","DOI":"10.2149\/tmh.2014-S04","article-title":"Morbidity control of schistosomiasis by mass drug administration: how can we do it best and what will it take to move on to elimination?","volume":"42","author":"Colley","year":"2014","journal-title":"Tropical Medicine and Health"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1038\/nature11924","article-title":"Adult somatic stem cells in the human parasite Schistosoma mansoni","volume":"494","author":"Collins","year":"2013","journal-title":"Nature"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1101\/gr.849004","article-title":"WebLogo: a sequence logo generator","volume":"14","author":"Crooks","year":"2004","journal-title":"Genome Research"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.molbiopara.2004.06.016","article-title":"The Schistosoma mansoni soluble proteome: a comparison across four life-cycle stages","volume":"138","author":"Curwen","year":"2004","journal-title":"Molecular and Biochemical Parasitology"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1017\/S0031182097001091","article-title":"A method for the isolation of schistosome eggs and miracidia free of contaminating host tissues","volume":"115","author":"Dalton","year":"1997","journal-title":"Parasitology"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1146\/annurev-genet-110711-155540","article-title":"Modernizing the nonhomologous end-joining repertoire: alternative and classical NHEJ share the stage","volume":"47","author":"Deriano","year":"2013","journal-title":"Annual Review of Genetics"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.dnarep.2018.06.005","article-title":"Formation and nucleolytic processing of Cas9-induced DNA breaks in human cells quantified by droplet digital PCR","volume":"68","author":"Dibitetto","year":"2018","journal-title":"DNA Repair"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/0035-9203(86)90126-4","article-title":"The schistosome egg granuloma: immunopathology in the cause of host protection or parasite survival?","volume":"80","author":"Doenhoff","year":"1986","journal-title":"Transactions of the Royal Society of Tropical Medicine and Hygiene"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1017\/S0031182000059503","article-title":"The purification, characterization, serological activity and hepatotoxic properties of two cationic glycoproteins (alpha 1 and omega 1) from Schistosoma mansoni eggs","volume":"103","author":"Dunne","year":"1991","journal-title":"Parasitology"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1007\/s11248-011-9548-0","article-title":"Human U6 promoter drives stronger shRNA activity than its schistosome orthologue in Schistosoma mansoni and human fibrosarcoma cells","volume":"21","author":"Duvoisin","year":"2012","journal-title":"Transgenic Research"},{"key":"bib24","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1128\/IAI.63.7.2532-2536.1995","article-title":"Suppressive effect of interleukin-4 neutralization differs for granulomas around Schistosoma mansoni eggs injected into mice compared with those around eggs laid in infected mice","volume":"63","author":"Eltoum","year":"1995","journal-title":"Infection and Immunity"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1084\/jem.20082460","article-title":"Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses","volume":"206","author":"Everts","year":"2009","journal-title":"The Journal of Experimental Medicine"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.1084\/jem.20111381","article-title":"Schistosome-derived omega-1 drives Th2 polarization by suppressing protein synthesis following internalization by the mannose receptor","volume":"209","author":"Everts","year":"2012","journal-title":"The Journal of Experimental Medicine"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1007\/s00281-012-0354-4","article-title":"Th2 responses in schistosomiasis","volume":"34","author":"Fairfax","year":"2012","journal-title":"Seminars in Immunopathology"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/j.ijpara.2015.08.005","article-title":"The Schistosoma mansoni T2 ribonuclease omega-1 modulates inflammasome-dependent IL-1\u03b2 secretion in macrophages","volume":"45","author":"Ferguson","year":"2015","journal-title":"International Journal for Parasitology"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.jnutbio.2015.09.010","article-title":"Association between omega-3 index and blood lipids in older Australians","volume":"27","author":"Ferguson","year":"2016","journal-title":"The Journal of Nutritional Biochemistry"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.molbiopara.2005.08.003","article-title":"Molecular characterization of omega-1: a hepatotoxic ribonuclease from Schistosoma mansoni eggs","volume":"144","author":"Fitzsimmons","year":"2005","journal-title":"Molecular and Biochemical Parasitology"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1161\/01.RES.0000038341.34243.64","article-title":"Cooperation between secretory phospholipase A2 and TNF-receptor superfamily signaling: implications for the inflammatory response in atherogenesis","volume":"91","author":"Fuentes","year":"2002","journal-title":"Circulation Research"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"e1006675","DOI":"10.1371\/journal.ppat.1006675","article-title":"Targeted mutagenesis in a human-parasitic nematode","volume":"13","author":"Gang","year":"2017","journal-title":"PLOS Pathogens"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1126\/science.aaa5945","article-title":"Genome editing. The mutagenic chain reaction: a method for converting heterozygous to homozygous mutations","volume":"348","author":"Gantz","year":"2015","journal-title":"Science"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/nrg.2015.16","article-title":"Single-cell genome sequencing: current state of the science","volume":"17","author":"Gawad","year":"2016","journal-title":"Nature Reviews Genetics"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1186\/s12885-015-1546-9","article-title":"M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide","volume":"15","author":"Genin","year":"2015","journal-title":"BMC Cancer"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/ncomms1433","article-title":"Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni","volume":"2","author":"Geyer","year":"2011","journal-title":"Nature Communications"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/S0301-472X(02)00806-8","article-title":"Gene quantification using real-time quantitative PCR: an emerging technology hits the mainstream","volume":"30","author":"Ginzinger","year":"2002","journal-title":"Experimental Hematology"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"42127","DOI":"10.1038\/srep42127","article-title":"Method for Dual Viral Vector Mediated CRISPR-Cas9 Gene Disruption in Primary Human Endothelial Cells","volume":"7","author":"Gong","year":"2017","journal-title":"Scientific Reports"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1016\/S0140-6736(06)69440-3","article-title":"Human schistosomiasis","volume":"368","author":"Gryseels","year":"2006","journal-title":"The Lancet"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"5375","DOI":"10.1038\/ncomms6375","article-title":"Omega-1 knockdown in Schistosoma mansoni eggs by lentivirus transduction reduces granuloma size in vivo","volume":"5","author":"Hagen","year":"2014","journal-title":"Nature Communications"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1146\/annurev-genet-051710-150955","article-title":"Regulation of homologous recombination in eukaryotes","volume":"44","author":"Heyer","year":"2010","journal-title":"Annual Review of Genetics"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1126\/science.1261139","article-title":"Medicine. Halting harmful helminths","volume":"346","author":"Hoffmann","year":"2014","journal-title":"Science"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.omtn.2017.08.016","article-title":"In\u00a0Vivo Knockout of the Vegfa Gene by Lentiviral Delivery of CRISPR\/Cas9 in Mouse Retinal Pigment Epithelium Cells","volume":"9","author":"Holmgaard","year":"2017","journal-title":"Molecular Therapy - Nucleic Acids"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1172\/JCI34261","article-title":"Helminth infections: the great neglected tropical diseases","volume":"118","author":"Hotez","year":"2008","journal-title":"Journal of Clinical Investigation"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"e3012","DOI":"10.1371\/journal.pntd.0003012","article-title":"Neglected parasitic infections and poverty in the United States","volume":"8","author":"Hotez","year":"2014","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"e2496","DOI":"10.1371\/journal.pntd.0002496","article-title":"Ten global \"hotspots\" for the neglected tropical diseases","volume":"8","author":"Hotez","year":"2014","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1016\/j.cell.2014.05.010","article-title":"Development and applications of CRISPR-Cas9 for genome engineering","volume":"157","author":"Hsu","year":"2014","journal-title":"Cell"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"15126","DOI":"10.1038\/s41598-018-33244-x","article-title":"High fidelity CRISPR\/Cas9 increases precise monoallelic and biallelic editing events in primordial germ cells","volume":"8","author":"Idoko-Akoh","year":"2018","journal-title":"Scientific Reports"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/s41588-018-0262-1","article-title":"Comparative genomics of the major parasitic worms","volume":"1","author":"International Helminth Genomes Consortium","year":"2019","journal-title":"Nature Genetics"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1126\/science.1225829","article-title":"A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity","volume":"337","author":"Jinek","year":"2012","journal-title":"Science"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s00427-009-0285-9","article-title":"The embryonic development of Schistosoma mansoni eggs: proposal for a new staging system","volume":"219","author":"Jurberg","year":"2009","journal-title":"Development Genes and Evolution"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"e2005504","DOI":"10.1371\/journal.pbio.2005504","article-title":"Dectin-1\/2-induced autocrine PGE2 signaling licenses dendritic cells to prime Th2 responses","volume":"16","author":"Kaisar","year":"2018","journal-title":"PLOS Biology"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s13071-016-1962-y","article-title":"Characterization of Schistosoma japonicum CP1412 protein as a novel member of the ribonuclease T2 molecule family with immune regulatory function","volume":"10","author":"Ke","year":"2017","journal-title":"Parasites & vectors"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/bs.pmbts.2017.09.003","article-title":"Dynamics of Indel Profiles Induced by Various CRISPR\/Cas9 Delivery Methods","volume":"152","author":"Kosicki","year":"2017","journal-title":"Progress in Molecular Biology and Translational Science"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal W and Clustal X version 2.0","volume":"23","author":"Larkin","year":"2007","journal-title":"Bioinformatics"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1128\/MMBR.00059-13","article-title":"DNA repair mechanisms and their biological roles in the malaria parasite Plasmodium falciparum","volume":"78","author":"Lee","year":"2014","journal-title":"Microbiology and Molecular Biology Reviews"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1590\/S0074-02762011000700007","article-title":"Towards an understanding of the epigenetics of schistosomes: a comparative epigenomic study","volume":"106","author":"Lepesant","year":"2011","journal-title":"Mem\u00f3rias Do Instituto Oswaldo Cruz"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1146\/annurev.biochem.052308.093131","article-title":"The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway","volume":"79","author":"Lieber","year":"2010","journal-title":"Annual Review of Biochemistry"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1017\/S0031182016000391","article-title":"Transgenesis in Strongyloides and related parasitic nematodes: historical perspectives, current functional genomic applications and progress towards gene disruption and editing","volume":"144","author":"Lok","year":"2017","journal-title":"Parasitology"},{"key":"bib61","doi-asserted-by":"publisher","DOI":"10.1101\/308213","article-title":"A web portal for gene expression across all life stages of Schistosoma mansoni","author":"Lu","year":"2018","journal-title":"bioRxiv"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.tibs.2010.02.002","article-title":"T2 Family ribonucleases: ancient enzymes with diverse roles","volume":"35","author":"Luhtala","year":"2010","journal-title":"Trends in Biochemical Sciences"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.jbiotec.2018.06.308","article-title":"Speed genome editing by transient CRISPR\/Cas9 targeting and large DNA fragment deletion","volume":"281","author":"Luo","year":"2018","journal-title":"Journal of Biotechnology"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1128\/IAI.70.2.427-433.2002","article-title":"Immunology of parasitic helminth infections","volume":"70","author":"MacDonald","year":"2002","journal-title":"Infection and Immunity"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"3127","DOI":"10.4049\/jimmunol.168.7.3127","article-title":"Cutting edge: polarized Th cell response induction by transferred antigen-pulsed dendritic cells is dependent on IL-4 or IL-12 production by recipient cells","volume":"168","author":"MacDonald","year":"2002","journal-title":"The Journal of Immunology"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1017\/S0031182009991211","article-title":"Culture for genetic manipulation of developmental stages of Schistosoma mansoni","volume":"137","author":"Mann","year":"2010","journal-title":"Parasitology"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"e1230","DOI":"10.1371\/journal.pntd.0001230","article-title":"Establishing transgenic schistosomes","volume":"5","author":"Mann","year":"2011","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1007\/s11248-013-9779-3","article-title":"Pseudotyped murine leukemia virus for schistosome transgenesis: approaches, methods and perspectives","volume":"23","author":"Mann","year":"2014","journal-title":"Transgenic Research"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"11130","DOI":"10.1128\/JVI.78.20.11130-11141.2004","article-title":"Relationships between infectious titer, capsid protein levels, and reverse transcriptase activities of diverse human immunodeficiency virus type 1 isolates","volume":"78","author":"Marozsan","year":"2004","journal-title":"Journal of Virology"},{"key":"bib70","doi-asserted-by":"publisher","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet.journal"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.ijpara.2009.10.014","article-title":"A comparative proteomic study of the undeveloped and developed Schistosoma mansoni egg and its contents: the miracidium, hatch fluid and secretions","volume":"40","author":"Mathieson","year":"2010","journal-title":"International Journal for Parasitology"},{"key":"bib72","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2018.10.008","article-title":"Mosaicism in CRISPR\/Cas9-mediated genome editing","author":"Mehravar","year":"2018","journal-title":"Developmental Biology"},{"key":"bib73","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/978-1-4939-7778-9_20","article-title":"Detection and Quantification of HDR and NHEJ Induced by Genome Editing at Endogenous Gene Loci Using Droplet Digital PCR","volume":"1768","author":"Miyaoka","year":"2018","journal-title":"Methods in Molecular Biology"},{"key":"bib74","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/0014-4894(92)90218-Y","article-title":"Schistosoma mansoni: control of hepatotoxicity and egg excretion by immune serum in infected immunosuppressed mice is schistosome species-specific, but not S. mansoni strain-specific","volume":"75","author":"Murare","year":"1992","journal-title":"Experimental Parasitology"},{"key":"bib75","doi-asserted-by":"publisher","first-page":"52","DOI":"10.4269\/ajtmh.1988.39.52","article-title":"The ultrastructure of the Schistosoma mansoni egg","volume":"39","author":"Neill","year":"1988","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"bib76","doi-asserted-by":"publisher","first-page":"W267","DOI":"10.1093\/nar\/gkw407","article-title":"Breaking-Cas-interactive design of guide RNAs for CRISPR-Cas experiments for ENSEMBL genomes","volume":"44","author":"Oliveros","year":"2016","journal-title":"Nucleic Acids Research"},{"key":"bib77","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/nature17664","article-title":"Efficient introduction of specific homozygous and heterozygous mutations using CRISPR\/Cas9","volume":"533","author":"Paquet","year":"2016","journal-title":"Nature"},{"key":"bib78","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1007\/s00018-009-8740-3","article-title":"DNA repair in mammalian cells: DNA double-strand break repair: how to fix a broken relationship","volume":"66","author":"Pardo","year":"2009","journal-title":"Cellular and Molecular Life Sciences : CMLS"},{"key":"bib79","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1111\/j.0105-2896.2004.00187.x","article-title":"Th2 response polarization during infection with the helminth parasite Schistosoma mansoni","volume":"201","author":"Pearce","year":"2004","journal-title":"Immunological Reviews"},{"key":"bib80","first-page":"1104","article-title":"Pillars article: downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. J. Exp. Med. 1991. 173: 159-166","volume":"189","author":"Pearce","year":"2012","journal-title":"Journal of Immunology"},{"key":"bib81","doi-asserted-by":"publisher","first-page":"2444","DOI":"10.1073\/pnas.85.8.2444","article-title":"Improved tools for biological sequence comparison","volume":"85","author":"Pearson","year":"1988","journal-title":"PNAS"},{"key":"bib82","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1038\/nbt.3583","article-title":"Analyzing CRISPR genome-editing experiments with CRISPResso","volume":"34","author":"Pinello","year":"2016","journal-title":"Nature Biotechnology"},{"key":"bib83","doi-asserted-by":"publisher","first-page":"e1455","DOI":"10.1371\/journal.pntd.0001455","article-title":"A systematically improved high quality genome and transcriptome of the human blood fluke Schistosoma mansoni","volume":"6","author":"Protasio","year":"2012","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"bib84","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.atherosclerosis.2011.09.003","article-title":"The use of THP-1 cells as a model for mimicking the function and regulation of monocytes and macrophages in the vasculature","volume":"221","author":"Qin","year":"2012","journal-title":"Atherosclerosis"},{"key":"bib85","doi-asserted-by":"publisher","first-page":"e1002820","DOI":"10.1371\/journal.ppat.1002820","article-title":"Germline transgenesis and insertional mutagenesis in Schistosoma mansoni mediated by murine leukemia virus","volume":"8","author":"Rinaldi","year":"2012","journal-title":"PLoS Pathogens"},{"key":"bib86","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.ijpara.2011.11.005","article-title":"An antibiotic selection marker for schistosome transgenesis","volume":"42","author":"Rinaldi","year":"2012","journal-title":"International Journal for Parasitology"},{"key":"bib87","doi-asserted-by":"publisher","first-page":"20459","DOI":"10.1073\/pnas.1010337107","article-title":"Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses","volume":"107","author":"Ritter","year":"2010","journal-title":"PNAS"},{"key":"bib88","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2010\/201026","article-title":"Myeloid cells in the tumor microenvironment: modulation of tumor angiogenesis and tumor inflammation","volume":"2010","author":"Schmid","year":"2010","journal-title":"Journal of Oncology"},{"key":"bib89","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.molbiopara.2009.02.003","article-title":"Molecular characterisation of kappa-5, a major antigenic glycoprotein from Schistosoma mansoni eggs","volume":"166","author":"Schramm","year":"2009","journal-title":"Molecular and Biochemical Parasitology"},{"key":"bib90","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/nmeth.3360","article-title":"Rapid reverse genetic screening using CRISPR in zebrafish","volume":"12","author":"Shah","year":"2015","journal-title":"Nature Methods"},{"key":"bib91","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/nrg3899","article-title":"High-throughput functional genomics using CRISPR-Cas9","volume":"16","author":"Shalem","year":"2015","journal-title":"Nature Reviews Genetics"},{"key":"bib92","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1084\/jem.20082462","article-title":"The major component in schistosome eggs responsible for conditioning dendritic cells for Th2 polarization is a T2 ribonuclease (omega-1)","volume":"206","author":"Steinfelder","year":"2009","journal-title":"The Journal of Experimental Medicine"},{"key":"bib93","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1007\/s11248-011-9556-0","article-title":"Prototypic chromatin insulator cHS4 protects retroviral transgene from silencing in Schistosoma mansoni","volume":"21","author":"Suttiprapa","year":"2012","journal-title":"Transgenic Research"},{"key":"bib94","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1017\/S003118201100134X","article-title":"Genetic manipulation of schistosomes--progress with integration competent vectors","volume":"139","author":"Suttiprapa","year":"2012","journal-title":"Parasitology"},{"key":"bib95","doi-asserted-by":"publisher","first-page":"e1005931","DOI":"10.1371\/journal.ppat.1005931","article-title":"HIV-1 Integrates Widely throughout the Genome of the Human Blood Fluke Schistosoma mansoni","volume":"12","author":"Suttiprapa","year":"2016","journal-title":"PLOS Pathogens"},{"key":"bib96","doi-asserted-by":"publisher","first-page":"4679","DOI":"10.1038\/s41598-018-22724-9","article-title":"Author Correction: Electroporation of mice zygotes with dual guide RNA\/Cas9 complexes for simple and efficient cloning-free genome editing","volume":"8","author":"Teixeira","year":"2018","journal-title":"Scientific Reports"},{"key":"bib97","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1038\/s41598-017-18826-5","article-title":"Electroporation of mice zygotes with dual guide RNA\/Cas9 complexes for simple and efficient cloning-free genome editing","volume":"8","author":"Teixeira","year":"2018","journal-title":"Scientific Reports"},{"key":"bib98","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1126\/science.1243106","article-title":"Genetic and molecular basis of drug resistance and species-specific drug action in schistosome parasites","volume":"342","author":"Valentim","year":"2013","journal-title":"Science"},{"key":"bib99","doi-asserted-by":"publisher","first-page":"e1004138","DOI":"10.1371\/journal.ppat.1004138","article-title":"Venus kinase receptors control reproduction in the platyhelminth parasite Schistosoma mansoni","volume":"10","author":"Vanderstraete","year":"2014","journal-title":"PLoS Pathogens"},{"key":"bib100","doi-asserted-by":"publisher","first-page":"e00768","DOI":"10.7554\/eLife.00768","article-title":"Functional genomic characterization of neoblast-like stem cells in larval Schistosoma mansoni","volume":"2","author":"Wang","year":"2013","journal-title":"eLife"},{"key":"bib101","doi-asserted-by":"publisher","first-page":"45910","DOI":"10.1038\/srep45910","article-title":"Production and glyco-engineering of immunomodulatory helminth glycoproteins in plants","volume":"7","author":"Wilbers","year":"2017","journal-title":"Scientific Reports"},{"key":"bib102","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1038\/nbt.2889","article-title":"Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells","volume":"32","author":"Wu","year":"2014","journal-title":"Nature Biotechnology"},{"key":"bib103","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.4049\/jimmunol.151.3.1430","article-title":"Analysis of cytokine mRNA expression during primary granuloma formation induced by eggs of Schistosoma mansoni","volume":"151","author":"Wynn","year":"1993","journal-title":"Journal of Immunology"},{"key":"bib104","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1111\/j.0105-2896.2004.00176.x","article-title":"Immunopathogenesis of schistosomiasis","volume":"201","author":"Wynn","year":"2004","journal-title":"Immunological Reviews"},{"key":"bib105","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02568-17","article-title":"Developmental Sensitivity in Schistosoma mansoni to Puromycin To Establish Drug Selection of Transgenic Schistosomes","volume":"62","author":"Yan","year":"2018","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"bib106","doi-asserted-by":"publisher","first-page":"17277","DOI":"10.1038\/s41598-018-34909-3","article-title":"Development of a multi-locus CRISPR gene drive system in budding yeast","volume":"8","author":"Yan","year":"2018","journal-title":"Scientific Reports"},{"key":"bib107","doi-asserted-by":"publisher","first-page":"10431","DOI":"10.1038\/ncomms10431","article-title":"ssODN-mediated knock-in with CRISPR-Cas for large genomic regions in zygotes","volume":"7","author":"Yoshimi","year":"2016","journal-title":"Nature Communications"},{"key":"bib108","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/ng.1065","article-title":"Whole-genome sequence of Schistosoma haematobium","volume":"44","author":"Young","year":"2012","journal-title":"Nature Genetics"},{"key":"bib109","doi-asserted-by":"publisher","first-page":"e98282","DOI":"10.1371\/journal.pone.0098282","article-title":"A PCR based protocol for detecting indel mutations induced by TALENs and CRISPR\/Cas9 in zebrafish","volume":"9","author":"Yu","year":"2014","journal-title":"PLoS ONE"},{"key":"bib110","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1111\/jipb.12622","article-title":"Multigene editing via CRISPR\/Cas9 guided by a single-sgRNA seed in Arabidopsis","volume":"60","author":"Yu","year":"2018","journal-title":"Journal of Integrative Plant Biology"},{"key":"bib111","doi-asserted-by":"publisher","first-page":"2709","DOI":"10.1002\/eji.201141429","article-title":"The S. mansoni glycoprotein \u03c9-1 induces Foxp3 expression in NOD mouse CD4\u207a T cells","volume":"41","author":"Zaccone","year":"2011","journal-title":"European Journal of Immunology"},{"key":"bib112","doi-asserted-by":"publisher","first-page":"e00861","DOI":"10.1128\/mBio.00861-15","article-title":"CRISPR-Cas9-Mediated Genome Editing in Leishmania donovani","volume":"6","author":"Zhang","year":"2015","journal-title":"mBio"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/41337\/elife-41337-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/41337\/elife-41337-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/41337","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:51:07Z","timestamp":1697057467000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/41337"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,15]]},"references-count":112,"alternative-id":["10.7554\/eLife.41337"],"URL":"https:\/\/doi.org\/10.7554\/elife.41337","archive":["CLOCKSS"],"relation":{"is-supplemented-by":[{"id-type":"uri","id":"https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/PRJNA415471","asserted-by":"subject"},{"id-type":"uri","id":"https:\/\/www.ebi.ac.uk\/ena\/data\/view\/PRJEB27995","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.41337.024","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.41337.025","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.734857559.793556532","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/358424","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,15]]},"article-number":"e41337"}}