{"id":"https://openalex.org/W4403834097","doi":"https://doi.org/10.1681/asn.2024s2rwxd87","title":"Genome Therapy in Kidney Organoids Reveals that Canonical NF\u03baB Signaling Governs Tubular Senescence, Cytotoxicity, and Immunogenicity in Response to Adeno-Associated Viruses (AAV)","display_name":"Genome Therapy in Kidney Organoids Reveals that Canonical NF\u03baB Signaling Governs Tubular Senescence, Cytotoxicity, and Immunogenicity in Response to Adeno-Associated Viruses (AAV)","publication_year":2024,"publication_date":"2024-10-01","ids":{"openalex":"https://openalex.org/W4403834097","doi":"https://doi.org/10.1681/asn.2024s2rwxd87"},"language":"en","primary_location":{"id":"doi:10.1681/asn.2024s2rwxd87","doi":"https://doi.org/10.1681/asn.2024s2rwxd87","is_oa":false,"landing_page_url":"https://doi.org/10.1681/asn.2024s2rwxd87","pdf_url":null,"source":{"id":"https://openalex.org/S115693375","display_name":"Journal of the American Society of Nephrology","issn_l":"1046-6673","issn":["1046-6673","1533-3450"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315620","host_organization_name":"American Society of Nephrology","host_organization_lineage":["https://openalex.org/P4310315620"],"host_organization_lineage_names":["American Society of Nephrology"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of the American Society of Nephrology","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5081692636","display_name":"Navin R. Gupta","orcid":"https://orcid.org/0000-0001-6445-3496","observed_orcids":["https://orcid.org/0000-0001-6445-3496"]},"institutions":[{"id":"https://openalex.org/I1330342723","display_name":"Mayo Clinic","ror":"https://ror.org/02qp3tb03","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1330342723"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Navin R. Gupta","raw_affiliation_strings":["Mayo Clinic Minnesota, Rochester, Minnesota, United States;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Mayo Clinic Minnesota, Rochester, Minnesota, United States;","institution_ids":["https://openalex.org/I1330342723"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5114140574","display_name":"Haruka Oishi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Haruka Oishi","raw_affiliation_strings":["Massachusetts General Hospital, Boston, Massachusetts, United States;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Massachusetts General Hospital, Boston, Massachusetts, United States;","institution_ids":["https://openalex.org/I4210087915"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5089325456","display_name":"Kenta Inomata","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kenta Inomata","raw_affiliation_strings":["Massachusetts General Hospital, Boston, Massachusetts, United States;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Massachusetts General Hospital, Boston, Massachusetts, United States;","institution_ids":["https://openalex.org/I4210087915"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5032821089","display_name":"Ryuji Morizane","orcid":"https://orcid.org/0000-0002-0377-5667","observed_orcids":["https://orcid.org/0000-0002-0377-5667"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210087915","display_name":"Massachusetts General Hospital","ror":"https://ror.org/002pd6e78","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210087915","https://openalex.org/I48633490"]},{"id":"https://openalex.org/I44142251","display_name":"Wyss Institute for Biologically Inspired Engineering","ror":"https://ror.org/008cfmj78","country_code":"US","type":"facility","lineage":["https://openalex.org/I136199984","https://openalex.org/I44142251"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ryuji Morizane","raw_affiliation_strings":["Harvard University Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, United States","Massachusetts General Hospital, Boston, Massachusetts, United States;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Harvard University Wyss Institute for Biologically Inspired Engineering, Boston, Massachusetts, United States","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I44142251"]},{"raw_affiliation_string":"Massachusetts General Hospital, Boston, Massachusetts, United States;","institution_ids":["https://openalex.org/I4210087915"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":4,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":0.2664,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":{"value":0.54874156,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":90,"max":94},"biblio":{"volume":"35","issue":"10S","first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10613","display_name":"Virus-based gene therapy research","score":0.9940999746322632,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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/T10613","display_name":"Virus-based gene therapy research","score":0.9940999746322632,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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/T10725","display_name":"RNA Interference and Gene Delivery","score":0.001500000013038516,"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/T10878","display_name":"CRISPR and Genetic Engineering","score":0.0013000000035390258,"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/kidney-organoids","display_name":"kidney organoids","score":0.921999990940094},{"id":"https://openalex.org/keywords/adeno-associated-virus","display_name":"adeno-associated virus","score":0.765999972820282},{"id":"https://openalex.org/keywords/crispr-gene-editing","display_name":"CRISPR gene editing","score":0.7960000038146973},{"id":"https://openalex.org/keywords/nf-kappab-signaling","display_name":"NF-\u03baB signaling","score":0.7210000157356262},{"id":"https://openalex.org/keywords/p21","display_name":"p21","score":0.7799999713897705},{"id":"https://openalex.org/keywords/cytotoxicity","display_name":"cytotoxicity","score":0.8140000104904175},{"id":"https://openalex.org/keywords/immunogenicity","display_name":"immunogenicity","score":0.9850000143051147},{"id":"https://openalex.org/keywords/interleukin-1beta","display_name":"IL-1\u03b2","score":0.9079999923706055},{"id":"https://openalex.org/keywords/nephron-loss","display_name":"nephron loss","score":0.6119999885559082},{"id":"https://openalex.org/keywords/renal-fibrosis","display_name":"renal fibrosis","score":0.7570000290870667},{"id":"https://openalex.org/keywords/preclinical-safety-evaluation","display_name":"preclinical safety","score":0.7120000123977661},{"id":"https://openalex.org/keywords/nephrotoxicity","display_name":"nephrotoxicity","score":0.847000002861023}],"concepts":[{"id":"https://openalex.org/C2780868878","wikidata":"https://www.wikidata.org/wiki/Q1660197","display_name":"Immunogenicity","level":3,"score":0.9046847820281982},{"id":"https://openalex.org/C522857546","wikidata":"https://www.wikidata.org/wiki/Q2070979","display_name":"Senescence","level":2,"score":0.7202886939048767},{"id":"https://openalex.org/C31695470","wikidata":"https://www.wikidata.org/wiki/Q11293125","display_name":"Organoid","level":2,"score":0.6142584085464478},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5918522477149963},{"id":"https://openalex.org/C109316439","wikidata":"https://www.wikidata.org/wiki/Q246181","display_name":"Cytotoxicity","level":3,"score":0.5709381103515625},{"id":"https://openalex.org/C141231307","wikidata":"https://www.wikidata.org/wiki/Q7020","display_name":"Genome","level":3,"score":0.5146992802619934},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.4867086708545685},{"id":"https://openalex.org/C2780091579","wikidata":"https://www.wikidata.org/wiki/Q9377","display_name":"Kidney","level":2,"score":0.45791780948638916},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.3836338520050049},{"id":"https://openalex.org/C159047783","wikidata":"https://www.wikidata.org/wiki/Q7215","display_name":"Virology","level":1,"score":0.3524585962295532},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.2983388304710388},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.2304607629776001},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.22959274053573608},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.17882376909255981},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.11405014991760254}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1681/asn.2024s2rwxd87","doi":"https://doi.org/10.1681/asn.2024s2rwxd87","is_oa":false,"landing_page_url":"https://doi.org/10.1681/asn.2024s2rwxd87","pdf_url":null,"source":{"id":"https://openalex.org/S115693375","display_name":"Journal of the American Society of Nephrology","issn_l":"1046-6673","issn":["1046-6673","1533-3450"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315620","host_organization_name":"American Society of Nephrology","host_organization_lineage":["https://openalex.org/P4310315620"],"host_organization_lineage_names":["American Society of Nephrology"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of the American Society of Nephrology","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9922999739646912}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4413051042","https://openalex.org/W4396991790","https://openalex.org/W7164515370","https://openalex.org/W4415546516","https://openalex.org/W2810575835","https://openalex.org/W6986881159","https://openalex.org/W4416066964","https://openalex.org/W2989734649","https://openalex.org/W4205441530","https://openalex.org/W2920915736"],"abstract_inverted_index":{"Background:":[0],"Genome":[1],"therapy":[2,27],"is":[3,138],"revolutionizing":[4],"the":[5,13,63,158,200,211,227],"treatment":[6],"of":[7,86,139,160,199,206,214,230,246],"inherited":[8],"diseases":[9],"by":[10,43,216],"directly":[11],"editing":[12,117,126],"human":[14,23,93,165],"genome.":[15],"Due":[16,58],"to":[17,20,35,52,59,169,176],"its":[18],"potential":[19],"irreversibly":[21],"alter":[22],"DNA,":[24],"systemic":[25],"gene":[26],"raises":[28],"significant":[29],"concerns,":[30],"demanding":[31],"a":[32,67,111,123,234],"new":[33],"approach":[34],"preclinical":[36],"evaluations.":[37],"These":[38],"concerns":[39],"are":[40,79],"further":[41],"illustrated":[42],"recent":[44],"tragedies":[45],"in":[46,128,142,220],"clinical":[47,129,144,244],"trials,":[48],"which":[49,241],"have":[50,91,132],"led":[51],"organ":[53,250],"failures":[54,251],"and":[55,88,95,100,102,172,187,196,252],"patient":[56],"fatalities.":[57],"high":[60],"blood":[61],"flow,":[62],"kidney":[64,77,98,108,231],"emerges":[65],"as":[66,110,233],"focal":[68],"point":[69],"for":[70,114,164,238],"drug-related":[71],"toxicity.":[72,153],"Methods:":[73],"Human":[74],"stem":[75],"cell-derived":[76],"organoids":[78,109,156,232],"nephron-rich,":[80],"highly":[81],"structured":[82],"3-dimensional":[83],"tissue":[84],"capable":[85],"exocrine":[87],"endocrine":[89],"functions,":[90],"modeled":[92],"genetic":[94],"non-genetic":[96],"disease,":[97],"injury":[99,195],"repair,":[101],"nephrotoxicity":[103],"testing.":[104],"Here":[105],"we":[106,179],"use":[107,145],"pre-clinical":[112,235],"platform":[113,237],"CRISPR":[115],"genome":[116,125,239],"via":[118],"adeno-associated":[119],"virus":[120],"(AAV)":[121],"delivery,":[122],"common":[124],"strategy":[127],"trials":[130,245],"that":[131,181,248],"raised":[133],"safety":[134],"concerns.":[135],"Although":[136],"AAV":[137,162,182],"limited":[140],"pathogenesis":[141],"humans,":[143],"has":[146],"required":[147],"supraphysiologic":[148],"titers":[149],"often":[150],"met":[151],"with":[152],"Results:":[154],"Kidney":[155],"validated":[157],"tropism":[159],"differing":[161],"serotypes":[163],"kidney.":[166],"Applying":[167],"immunostaining":[168],"organoid":[170],"cryosections":[171],"electrochemiluminescence-based":[173],"mesoscale":[174],"discovery":[175],"their":[177],"supernatants,":[178],"found":[180],"drives":[183],"tubular":[184,194],"genotoxicity,":[185],"cytotoxicity,":[186],"immunogenicity.":[188],"RNA-sequencing":[189],"identified":[190],"an":[191],"association":[192],"between":[193],"IL-1\u03b2":[197],"activation":[198],"canonical":[201,207],"NF\u03baB":[202,208],"pathway.":[203],"Targeted":[204],"inhibition":[205],"signaling":[209],"prevented":[210],"fibrotic":[212],"loss":[213],"nephrons":[215],"ameliorating":[217],"p21+":[218],"senescence":[219],"injured":[221],"tubules.":[222],"Conclusion:":[223],"Our":[224],"findings":[225],"demonstrate":[226],"translational":[228],"utility":[229],"testing":[236],"therapy,":[240],"may":[242],"inform":[243],"strategies":[247],"limit":[249],"death.":[253],"Funding:":[254],"NIDDK":[255],"Support":[256]},"counts_by_year":[{"year":2025,"cited_by_count":1}],"updated_date":"2026-10-22T18:32:59.640997","created_date":"2024-10-29T00:00:00"}