{"id":"https://openalex.org/W4211089348","doi":"https://doi.org/10.1016/j.omtn.2022.02.004","title":"Engineering miRNA features into siRNAs: Guide-strand bulges are compatible with gene repression","display_name":"Engineering miRNA features into siRNAs: Guide-strand bulges are compatible with gene repression","publication_year":2022,"publication_date":"2022-02-10","ids":{"openalex":"https://openalex.org/W4211089348","doi":"https://doi.org/10.1016/j.omtn.2022.02.004","pmid":"https://pubmed.ncbi.nlm.nih.gov/35251767","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/8881630"},"language":"en","primary_location":{"id":"doi:10.1016/j.omtn.2022.02.004","doi":"https://doi.org/10.1016/j.omtn.2022.02.004","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.omtn.2022.02.004","pdf_url":"http://www.cell.com/article/S2162253122000324/pdf","source":{"id":"https://openalex.org/S2764969478","display_name":"Molecular Therapy \u2014 Nucleic Acids","issn_l":"2162-2531","issn":["2162-2531"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-d","jufo-1","ki-jl-1","norway-1","poland-140","vabb-shw"],"host_organization":"https://openalex.org/P4310315673","host_organization_name":"Cell Press","host_organization_lineage":["https://openalex.org/P4310315673","https://openalex.org/P4310320990"],"host_organization_lineage_names":["Cell Press","Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Therapy Nucleic Acids","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"http://www.cell.com/article/S2162253122000324/pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5023200347","display_name":"Judith Hauptmann","orcid":"https://orcid.org/0000-0001-9098-6763","observed_orcids":["https://orcid.org/0000-0001-9098-6763"]},"institutions":[{"id":"https://openalex.org/I4210102048","display_name":"Silence Therapeutics (Germany)","ror":"https://ror.org/01hwrdv70","country_code":"DE","type":"company","lineage":["https://openalex.org/I4210102048","https://openalex.org/I4210134646"]}],"countries":["DE"],"is_corresponding":true,"raw_author_name":"Judith Hauptmann","raw_affiliation_strings":["Silence Therapeutics GmbH, Robert-Roessle-Strasse 10, 13125 Berlin, Germany"],"raw_orcid":"https://orcid.org/0000-0001-9098-6763","affiliations":[{"raw_affiliation_string":"Silence Therapeutics GmbH, Robert-Roessle-Strasse 10, 13125 Berlin, Germany","institution_ids":["https://openalex.org/I4210102048"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5076349364","display_name":"Vivien Hehne","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210102048","display_name":"Silence Therapeutics (Germany)","ror":"https://ror.org/01hwrdv70","country_code":"DE","type":"company","lineage":["https://openalex.org/I4210102048","https://openalex.org/I4210134646"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Vivien Hehne","raw_affiliation_strings":["Silence Therapeutics GmbH, Robert-Roessle-Strasse 10, 13125 Berlin, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Silence Therapeutics GmbH, Robert-Roessle-Strasse 10, 13125 Berlin, Germany","institution_ids":["https://openalex.org/I4210102048"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5039244922","display_name":"Melanie Balzer","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210102048","display_name":"Silence Therapeutics (Germany)","ror":"https://ror.org/01hwrdv70","country_code":"DE","type":"company","lineage":["https://openalex.org/I4210102048","https://openalex.org/I4210134646"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Melanie Balzer","raw_affiliation_strings":["Silence Therapeutics GmbH, Robert-Roessle-Strasse 10, 13125 Berlin, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Silence Therapeutics GmbH, Robert-Roessle-Strasse 10, 13125 Berlin, Germany","institution_ids":["https://openalex.org/I4210102048"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5026891223","display_name":"Lucas Bethge","orcid":"https://orcid.org/0000-0001-9779-3251","observed_orcids":["https://orcid.org/0000-0001-9779-3251"]},"institutions":[{"id":"https://openalex.org/I4210102048","display_name":"Silence Therapeutics (Germany)","ror":"https://ror.org/01hwrdv70","country_code":"DE","type":"company","lineage":["https://openalex.org/I4210102048","https://openalex.org/I4210134646"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Lucas Bethge","raw_affiliation_strings":["Silence Therapeutics GmbH, Robert-Roessle-Strasse 10, 13125 Berlin, Germany"],"raw_orcid":"https://orcid.org/0000-0001-9779-3251","affiliations":[{"raw_affiliation_string":"Silence Therapeutics GmbH, Robert-Roessle-Strasse 10, 13125 Berlin, Germany","institution_ids":["https://openalex.org/I4210102048"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5068411806","display_name":"Marie Lindholm","orcid":"https://orcid.org/0000-0002-0975-2394","observed_orcids":["https://orcid.org/0000-0002-0975-2394"]},"institutions":[{"id":"https://openalex.org/I4210102048","display_name":"Silence Therapeutics (Germany)","ror":"https://ror.org/01hwrdv70","country_code":"DE","type":"company","lineage":["https://openalex.org/I4210102048","https://openalex.org/I4210134646"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Marie Wikstrom Lindholm","raw_affiliation_strings":["Silence Therapeutics GmbH, Robert-Roessle-Strasse 10, 13125 Berlin, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Silence Therapeutics GmbH, Robert-Roessle-Strasse 10, 13125 Berlin, Germany","institution_ids":["https://openalex.org/I4210102048"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5023200347"],"corresponding_institution_ids":["https://openalex.org/I4210102048"],"apc_list":{"value":3900,"currency":"USD","value_usd":3900},"apc_paid":{"value":3900,"currency":"USD","value_usd":3900},"fwci":0.2174,"has_fulltext":false,"cited_by_count":5,"citation_normalized_percentile":{"value":0.34270159,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":96},"biblio":{"volume":"27","issue":null,"first_page":"1116","last_page":"1126"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10725","display_name":"RNA Interference and Gene Delivery","score":0.9990000128746033,"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/T10725","display_name":"RNA Interference and Gene Delivery","score":0.9990000128746033,"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":0.0003000000142492354,"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":9.999999747378752e-05,"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/sirna","display_name":"siRNA","score":0.6299999952316284},{"id":"https://openalex.org/keywords/passenger-strand","display_name":"passenger strand","score":0.47999998927116394},{"id":"https://openalex.org/keywords/rna-induced-silencing-complex","display_name":"RNA-induced silencing complex","score":0.8270000219345093},{"id":"https://openalex.org/keywords/galnac-conjugated-sirna","display_name":"GalNAc-conjugated siRNA","score":0.8579999804496765},{"id":"https://openalex.org/keywords/prealbumin","display_name":"prealbumin","score":0.9399999976158142},{"id":"https://openalex.org/keywords/gene-silencing","display_name":"gene silencing","score":0.7360000014305115},{"id":"https://openalex.org/keywords/off-target-effects","display_name":"off-target effects","score":0.9039999842643738},{"id":"https://openalex.org/keywords/sirna-design","display_name":"siRNA design","score":0.5759999752044678}],"concepts":[{"id":"https://openalex.org/C22615655","wikidata":"https://www.wikidata.org/wiki/Q203221","display_name":"Small interfering RNA","level":4,"score":0.7109947204589844},{"id":"https://openalex.org/C119056186","wikidata":"https://www.wikidata.org/wiki/Q1431332","display_name":"Gene silencing","level":3,"score":0.5987327098846436},{"id":"https://openalex.org/C145059251","wikidata":"https://www.wikidata.org/wiki/Q310899","display_name":"microRNA","level":3,"score":0.5237025022506714},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.521185576915741},{"id":"https://openalex.org/C95911042","wikidata":"https://www.wikidata.org/wiki/Q6432361","display_name":"Sense strand","level":4,"score":0.4729703962802887},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.4595019817352295},{"id":"https://openalex.org/C166703698","wikidata":"https://www.wikidata.org/wiki/Q201993","display_name":"RNA interference","level":4,"score":0.45133382081985474},{"id":"https://openalex.org/C67705224","wikidata":"https://www.wikidata.org/wiki/Q11053","display_name":"RNA","level":3,"score":0.44896838068962097},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.43861517310142517},{"id":"https://openalex.org/C111335760","wikidata":"https://www.wikidata.org/wiki/Q95385166","display_name":"Luciferase","level":4,"score":0.4357033967971802},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.4341932535171509},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3812141716480255},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.329248309135437},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.2619211971759796},{"id":"https://openalex.org/C54009773","wikidata":"https://www.wikidata.org/wiki/Q1429031","display_name":"Transfection","level":3,"score":0.25504204630851746}],"mesh":[],"locations_count":4,"locations":[{"id":"doi:10.1016/j.omtn.2022.02.004","doi":"https://doi.org/10.1016/j.omtn.2022.02.004","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.omtn.2022.02.004","pdf_url":"http://www.cell.com/article/S2162253122000324/pdf","source":{"id":"https://openalex.org/S2764969478","display_name":"Molecular Therapy \u2014 Nucleic Acids","issn_l":"2162-2531","issn":["2162-2531"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-d","jufo-1","ki-jl-1","norway-1","poland-140","vabb-shw"],"host_organization":"https://openalex.org/P4310315673","host_organization_name":"Cell Press","host_organization_lineage":["https://openalex.org/P4310315673","https://openalex.org/P4310320990"],"host_organization_lineage_names":["Cell Press","Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Therapy Nucleic Acids","raw_type":"journal-article"},{"id":"pmid:35251767","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/35251767","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular therapy. Nucleic acids","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:8881630","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8881630/","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Mol Ther Nucleic Acids","raw_type":"Text"},{"id":"pmh:oai:doaj.org/article:4bd1ec5c027246ee891115d53da7c241","doi":null,"is_oa":true,"landing_page_url":"https://doaj.org/article/4bd1ec5c027246ee891115d53da7c241","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-sa","license_id":"https://openalex.org/licenses/cc-by-sa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Molecular Therapy: Nucleic Acids, Vol 27, Iss , Pp 1116-1126 (2022)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.1016/j.omtn.2022.02.004","doi":"https://doi.org/10.1016/j.omtn.2022.02.004","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.omtn.2022.02.004","pdf_url":"http://www.cell.com/article/S2162253122000324/pdf","source":{"id":"https://openalex.org/S2764969478","display_name":"Molecular Therapy \u2014 Nucleic Acids","issn_l":"2162-2531","issn":["2162-2531"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-d","jufo-1","ki-jl-1","norway-1","poland-140","vabb-shw"],"host_organization":"https://openalex.org/P4310315673","host_organization_name":"Cell Press","host_organization_lineage":["https://openalex.org/P4310315673","https://openalex.org/P4310320990"],"host_organization_lineage_names":["Cell Press","Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Therapy Nucleic Acids","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.4000000059604645,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4211089348.pdf"},"referenced_works_count":35,"referenced_works":["https://openalex.org/W1920303762","https://openalex.org/W1984085632","https://openalex.org/W2001583023","https://openalex.org/W2050642406","https://openalex.org/W2051010056","https://openalex.org/W2053003053","https://openalex.org/W2054109341","https://openalex.org/W2074675420","https://openalex.org/W2075257237","https://openalex.org/W2100932663","https://openalex.org/W2101543035","https://openalex.org/W2111831519","https://openalex.org/W2131246621","https://openalex.org/W2134629862","https://openalex.org/W2135837360","https://openalex.org/W2139115320","https://openalex.org/W2139871850","https://openalex.org/W2140654254","https://openalex.org/W2141729181","https://openalex.org/W2150116770","https://openalex.org/W2150583958","https://openalex.org/W2152006478","https://openalex.org/W2155512005","https://openalex.org/W2157287222","https://openalex.org/W2161560970","https://openalex.org/W2167754184","https://openalex.org/W2170103998","https://openalex.org/W2265699209","https://openalex.org/W2284266226","https://openalex.org/W2592524531","https://openalex.org/W2725456841","https://openalex.org/W2827323865","https://openalex.org/W2957005848","https://openalex.org/W3027335810","https://openalex.org/W4211064852"],"related_works":["https://openalex.org/W2075257237","https://openalex.org/W16907669","https://openalex.org/W2007501617","https://openalex.org/W3025795337","https://openalex.org/W2331666973","https://openalex.org/W2530045699","https://openalex.org/W2613903261","https://openalex.org/W2105258749","https://openalex.org/W1970542828","https://openalex.org/W2161872337"],"abstract_inverted_index":{"Synthetic":[0],"siRNA":[1,111],"guide":[2,93,121],"strands":[3],"are":[4,26],"typically":[5],"designed":[6],"with":[7,22,55,86,112,152],"perfect":[8],"complementarity":[9],"to":[10,57,171],"the":[11,15,42,92,120,127,167,172,175],"passenger":[12,43],"strand":[13,94,122],"and":[14,30,76,101,163,191],"target":[16,138,184,189],"mRNA.":[17],"We":[18,62,177],"examined":[19],"whether":[20],"siRNAs":[21,85],"intentional":[23],"guide-strand":[24,48,65,154,181],"bulges":[25,59,66,87,182],"functional":[27],"in":[28,31,97,102,104,132,188],"vitro":[29],"vivo":[32,103,107],".":[33],"Importantly,":[34],"this":[35],"was":[36,123],"done":[37],"by":[38],"systematic":[39],"shortening":[40],"of":[41,74,91,119,166,174],"strand,":[44],"evaluating":[45],"identical":[46],"19-mer":[47],"sequences":[49,139],"but":[50],"forcing":[51],"them":[52],"into":[53],"conformations":[54],"1-":[56,162],"4-nt":[58],"after":[60],"annealing.":[61],"demonstrate":[63],"that":[64,83,144,179],"can":[67,186],"be":[68,194],"well":[69],"tolerated":[70],"at":[71,88,116],"several":[72],"positions":[73,90],"unmodified":[75],"modified":[77],"siRNAs.":[78],"Beyond":[79],"that,":[80],"we":[81],"show":[82],"GalNAc-conjugated":[84,110],"certain":[89],"repress":[95],"transthyretin":[96],"murine":[98],"primary":[99],"hepatocytes":[100],"mice.":[105],"In":[106],",":[108],"a":[109,113,133,153],"1-nt":[114],"bulge":[115],"position":[117],"14":[118],"as":[124,126,196],"active":[125],"perfectly":[128],"complementary":[129],"siRNA.":[130],"Finally,":[131],"luciferase":[134,157],"reporter":[135,168],"system,":[136],"mRNA":[137],"were":[140,159,169],"systematically":[141],"shortened":[142],"so":[143],"RNA-induced":[145],"silencing":[146],"complex":[147],"activity":[148],"could":[149],"only":[150],"occur":[151],"bulge.":[155],"Here,":[156],"reporters":[158],"repressed":[160],"when":[161],"2-nt":[164],"deletions":[165],"applied":[170],"edges":[173],"sequence.":[176],"conclude":[178],"some":[180],"versus":[183],"transcript":[185],"result":[187],"repression":[190],"therefore":[192],"should":[193],"evaluated":[195],"off-target":[197],"risks.":[198]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":2}],"updated_date":"2026-11-10T11:39:43.021295","created_date":"2022-02-13T00:00:00"}
