{"id":"https://openalex.org/W7213468809","doi":"https://doi.org/10.64898/2026.09.14.751601","title":"CRISPR/Cas9 Optimization Using Electronic Genome Mapping: Potential Role for Studying Human Genetic Disease","display_name":"CRISPR/Cas9 Optimization Using Electronic Genome Mapping: Potential Role for Studying Human Genetic Disease","publication_year":2026,"publication_date":"2026-09-17","ids":{"openalex":"https://openalex.org/W7213468809","doi":"https://doi.org/10.64898/2026.09.14.751601"},"language":"en","primary_location":{"id":"doi:10.64898/2026.09.14.751601","doi":"https://doi.org/10.64898/2026.09.14.751601","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.14.751601","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/17/2026.09.14.751601.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/17/2026.09.14.751601.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5151957151","display_name":"Lindsay Schneider Opsahl","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210102647","display_name":"Nabsys (United States)","ror":"https://ror.org/01bcsqk59","country_code":"US","type":"company","lineage":["https://openalex.org/I4210102647"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Lindsay Opsahl","raw_affiliation_strings":["Nabsys 2.0 LLC; Providence, RI USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Nabsys 2.0 LLC; Providence, RI USA","institution_ids":["https://openalex.org/I4210102647"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Wentao Huang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210102647","display_name":"Nabsys (United States)","ror":"https://ror.org/01bcsqk59","country_code":"US","type":"company","lineage":["https://openalex.org/I4210102647"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Wentao Huang","raw_affiliation_strings":["Nabsys 2.0 LLC; Providence, RI USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Nabsys 2.0 LLC; Providence, RI USA","institution_ids":["https://openalex.org/I4210102647"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5151935585","display_name":"Syndi Koltz","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210102647","display_name":"Nabsys (United States)","ror":"https://ror.org/01bcsqk59","country_code":"US","type":"company","lineage":["https://openalex.org/I4210102647"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Syndi Koltz","raw_affiliation_strings":["Nabsys 2.0 LLC; Providence, RI USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Nabsys 2.0 LLC; Providence, RI USA","institution_ids":["https://openalex.org/I4210102647"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5067931595","display_name":"Kaylee L. Mathews","orcid":"https://orcid.org/0000-0002-7197-0456","observed_orcids":["https://orcid.org/0000-0002-7197-0456"]},"institutions":[{"id":"https://openalex.org/I4210102647","display_name":"Nabsys (United States)","ror":"https://ror.org/01bcsqk59","country_code":"US","type":"company","lineage":["https://openalex.org/I4210102647"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kaylee L. Mathews","raw_affiliation_strings":["Nabsys 2.0 LLC; Providence, RI USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Nabsys 2.0 LLC; Providence, RI USA","institution_ids":["https://openalex.org/I4210102647"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5028713727","display_name":"John F. Thompson","orcid":"https://orcid.org/0000-0001-8568-3311","observed_orcids":["https://orcid.org/0000-0001-8568-3311","https://orcid.org/0000-0003-0443-9590"]},"institutions":[{"id":"https://openalex.org/I4210102647","display_name":"Nabsys (United States)","ror":"https://ror.org/01bcsqk59","country_code":"US","type":"company","lineage":["https://openalex.org/I4210102647"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"John F. Thompson","raw_affiliation_strings":["Nabsys 2.0 LLC; Providence, RI USA"],"raw_orcid":"https://orcid.org/0000-0001-8568-3311","affiliations":[{"raw_affiliation_string":"Nabsys 2.0 LLC; Providence, RI USA","institution_ids":["https://openalex.org/I4210102647"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5028713727"],"corresponding_institution_ids":["https://openalex.org/I4210102647"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":1,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10878","display_name":"CRISPR and Genetic Engineering","score":1.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10878","display_name":"CRISPR and Genetic Engineering","score":1.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10432","display_name":"DNA and Nucleic Acid Chemistry","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12610","display_name":"RNA regulation and disease","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/crispr-cas9","display_name":"CRISPR/Cas9","score":0.9760000109672546},{"id":"https://openalex.org/keywords/off-target-binding","display_name":"off-target binding","score":0.9909999966621399},{"id":"https://openalex.org/keywords/friedreich-ataxia","display_name":"Friedreich's ataxia","score":0.8889999985694885},{"id":"https://openalex.org/keywords/repeat-expansion-disorders","display_name":"repeat expansion disorders","score":0.7269999980926514},{"id":"https://openalex.org/keywords/pam-site","display_name":"PAM site","score":0.7509999871253967},{"id":"https://openalex.org/keywords/seed-region","display_name":"seed region","score":0.878000020980835},{"id":"https://openalex.org/keywords/dcas9","display_name":"dCas9","score":0.6539999842643738}],"concepts":[{"id":"https://openalex.org/C98108389","wikidata":"https://www.wikidata.org/wiki/Q412563","display_name":"CRISPR","level":3,"score":0.7968000173568726},{"id":"https://openalex.org/C97702854","wikidata":"https://www.wikidata.org/wiki/Q4039747","display_name":"Guide RNA","level":5,"score":0.7696999907493591},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.7325000166893005},{"id":"https://openalex.org/C132455925","wikidata":"https://www.wikidata.org/wiki/Q16965677","display_name":"Cas9","level":4,"score":0.6049000024795532},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5911999940872192},{"id":"https://openalex.org/C141231307","wikidata":"https://www.wikidata.org/wiki/Q7020","display_name":"Genome","level":3,"score":0.5773000121116638},{"id":"https://openalex.org/C197077220","wikidata":"https://www.wikidata.org/wiki/Q720988","display_name":"Human genome","level":4,"score":0.5282999873161316},{"id":"https://openalex.org/C107824862","wikidata":"https://www.wikidata.org/wiki/Q616005","display_name":"Binding site","level":2,"score":0.4952999949455261},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.4832000136375427},{"id":"https://openalex.org/C66746571","wikidata":"https://www.wikidata.org/wiki/Q1134833","display_name":"ENCODE","level":3,"score":0.4796000123023987},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.4681999981403351},{"id":"https://openalex.org/C2778112365","wikidata":"https://www.wikidata.org/wiki/Q3511065","display_name":"Sequence (biology)","level":2,"score":0.43470001220703125},{"id":"https://openalex.org/C144501496","wikidata":"https://www.wikidata.org/wiki/Q5533489","display_name":"Genome editing","level":4,"score":0.4092999994754791},{"id":"https://openalex.org/C32795469","wikidata":"https://www.wikidata.org/wiki/Q5156430","display_name":"Complementary sequences","level":2,"score":0.38920000195503235},{"id":"https://openalex.org/C47042493","wikidata":"https://www.wikidata.org/wiki/Q265799","display_name":"Human genetics","level":3,"score":0.3862999975681305},{"id":"https://openalex.org/C51639874","wikidata":"https://www.wikidata.org/wiki/Q167149","display_name":"Plasma protein binding","level":2,"score":0.38040000200271606},{"id":"https://openalex.org/C129312508","wikidata":"https://www.wikidata.org/wiki/Q133686","display_name":"Oligonucleotide","level":3,"score":0.3781999945640564},{"id":"https://openalex.org/C51679486","wikidata":"https://www.wikidata.org/wiki/Q380546","display_name":"DNA sequencing","level":3,"score":0.3490000069141388},{"id":"https://openalex.org/C94966510","wikidata":"https://www.wikidata.org/wiki/Q2252764","display_name":"DNA-binding protein","level":4,"score":0.34389999508857727},{"id":"https://openalex.org/C3662595","wikidata":"https://www.wikidata.org/wiki/Q5205743","display_name":"DNA binding site","level":5,"score":0.33160001039505005},{"id":"https://openalex.org/C189206191","wikidata":"https://www.wikidata.org/wiki/Q222046","display_name":"Genomics","level":4,"score":0.28940001130104065},{"id":"https://openalex.org/C174510640","wikidata":"https://www.wikidata.org/wiki/Q489618","display_name":"HEK 293 cells","level":3,"score":0.2883000075817108},{"id":"https://openalex.org/C2988867146","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Human disease","level":3,"score":0.2863999903202057},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.267300009727478},{"id":"https://openalex.org/C19843653","wikidata":"https://www.wikidata.org/wiki/Q213907","display_name":"Model organism","level":3,"score":0.2646999955177307},{"id":"https://openalex.org/C45484198","wikidata":"https://www.wikidata.org/wiki/Q827246","display_name":"Sequence alignment","level":4,"score":0.2644999921321869},{"id":"https://openalex.org/C192953774","wikidata":"https://www.wikidata.org/wiki/Q7307127","display_name":"Reference genome","level":4,"score":0.25589999556541443}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.09.14.751601","doi":"https://doi.org/10.64898/2026.09.14.751601","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.14.751601","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/17/2026.09.14.751601.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.09.14.751601","doi":"https://doi.org/10.64898/2026.09.14.751601","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.09.14.751601","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/09/17/2026.09.14.751601.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc","license_id":"https://openalex.org/licenses/cc-by-nc","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.504800021648407,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7213468809.pdf","grobid_xml":"https://content.openalex.org/works/W7213468809.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W1506494596","https://openalex.org/W2077659966","https://openalex.org/W4366742973","https://openalex.org/W1821692337","https://openalex.org/W3153228594","https://openalex.org/W2794852126","https://openalex.org/W2030994161","https://openalex.org/W7166525375","https://openalex.org/W4289745822","https://openalex.org/W2746937837"],"abstract_inverted_index":{"Abstract":[0],"CRISPR":[1,213,248],"Cas9\u2019s":[2],"ability":[3,52],"to":[4,53,79,88,112,118,125,163,175,211,232],"bind":[5,113],"targeted":[6,64],"and":[7,10,17,136,180,215,221,235,249,252],"non-targeted":[8],"sites":[9,122,126,179,190],"its":[11,51,253],"functional":[12],"interactions":[13],"with":[14,50,127,188,270],"other":[15,212],"proteins":[16,220,234],"domains":[18],"have":[19],"been":[20],"studied":[21],"using":[22,31,97],"many":[23,202],"technologies.":[24],"These":[25],"studies":[26],"are":[27,268],"often":[28],"limited":[29],"by":[30,36],"oligos":[32],"as":[33,143],"substrates":[34],"or":[35],"a":[37,84,98,107],"reliance":[38],"on":[39],"predicted":[40],"binding":[41,67,83],"sites.":[42,116],"We":[43,159],"show":[44],"how":[45,60,165],"electronic":[46],"genome":[47,72,266],"mapping":[48],"(EGM)":[49],"detect":[54],"single-molecule":[55],"DNA":[56,177],"nicks":[57],"can":[58,172,199],"determine":[59,164],"gRNA":[61,99,121,131,153],"mismatches":[62,128,150],"impact":[63],"versus":[65],"off-target":[66,157,204],"across":[68],"the":[69,89,152,168,195,225,240,244,257,264],"whole":[70],"human":[71,265,271],"in":[73,256,263],"vitro":[74],".":[75],"Cas9":[76],"was":[77,123],"found":[78],"be":[80,173,209],"capable":[81],"of":[82,115,218,228,247,259],"single":[85,149],"site":[86,135],"adjacent":[87],"FXN":[90],"repeat":[91,261,272],"expansion":[92,273],"responsible":[93],"for":[94,101,145],"Friedreich":[95],"Ataxia":[96],"specific":[100,260],"that":[102,267],"sequence":[103,109],"while":[104],"gRNAs":[105],"matching":[106],"repetitive":[108],"were":[110,141],"able":[111],"hundreds":[114],"Binding":[117],"perfectly":[119],"matched":[120],"compared":[124],"at":[129],"each":[130],"position.":[132],"The":[133],"PAM":[134],"nearby":[137,176],"seed":[138],"region":[139],"bases":[140],"confirmed":[142],"critical":[144],"binding.":[146,158],"In":[147],"contrast,":[148],"toward":[151],"5\u2019":[154],"end":[155],"allowed":[156],"also":[160,239],"used":[161,231],"EGM":[162,198,229,250],"physically":[166],"close":[167],"bound":[169],"dCas9/gRNA":[170],"complex":[171],"relative":[174],"modification":[178],"still":[181],"allow":[182],"activity.":[183],"Bound":[184],"CRISPR/dCas9":[185],"inhibits":[186],"nickases":[187],"recognition":[189],"4-7":[191],"bp":[192],"away":[193],"from":[194],"gRNA/PAM.":[196],"Because":[197],"simultaneously":[200],"evaluate":[201],"mismatched":[203],"sites,":[205],"these":[206],"insights":[207],"may":[208],"extended":[210],"systems":[214],"enable":[216],"optimization":[217],"Cas":[219],"gRNAs.":[222],"This":[223,237],"is":[224,238],"first":[226,241],"example":[227],"being":[230],"characterize":[233],"RNAs.":[236],"study":[242],"demonstrating":[243],"combined":[245],"application":[246],"methodology":[251],"potential":[254],"role":[255],"detection":[258],"regions":[262],"associated":[269],"disorders.":[274]},"counts_by_year":[{"year":2026,"cited_by_count":1}],"updated_date":"2026-11-01T11:40:01.658920","created_date":"2026-09-17T00:00:00"}