{"id":"https://openalex.org/W7225811894","doi":"https://doi.org/10.1021/acs.molpharmaceut.6c01077","title":"RiboGreen-Based Encapsulation Efficiency Measurement for Lipid Nanoparticles: Evaluation of Total RNA Assay and Surrogate-Matrix Correction of Free RNA Fluorescence Bias","display_name":"RiboGreen-Based Encapsulation Efficiency Measurement for Lipid Nanoparticles: Evaluation of Total RNA Assay and Surrogate-Matrix Correction of Free RNA Fluorescence Bias","publication_year":2026,"publication_date":"2026-11-11","ids":{"openalex":"https://openalex.org/W7225811894","doi":"https://doi.org/10.1021/acs.molpharmaceut.6c01077"},"language":"en","primary_location":{"id":"doi:10.1021/acs.molpharmaceut.6c01077","doi":"https://doi.org/10.1021/acs.molpharmaceut.6c01077","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.molpharmaceut.6c01077","pdf_url":null,"source":{"id":"https://openalex.org/S204562082","display_name":"Molecular Pharmaceutics","issn_l":"1543-8384","issn":["1543-8384","1543-8392"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-c","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Pharmaceutics","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"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/A5161455900","display_name":"Yun Zhu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I168537998","display_name":"Eli Lilly (United States)","ror":"https://ror.org/01qat3289","country_code":"US","type":"company","lineage":["https://openalex.org/I168537998"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Yun Zhu","raw_affiliation_strings":["Eli Lilly and Company, Lilly Seaport Innovation Center , , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Eli Lilly and Company, Lilly Seaport Innovation Center , , , ,","institution_ids":["https://openalex.org/I168537998"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5070634976","display_name":"Zhe Tan","orcid":"https://orcid.org/0000-0002-3518-0772","observed_orcids":["https://orcid.org/0000-0002-3518-0772"]},"institutions":[{"id":"https://openalex.org/I168537998","display_name":"Eli Lilly (United States)","ror":"https://ror.org/01qat3289","country_code":"US","type":"company","lineage":["https://openalex.org/I168537998"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Zhe Tan","raw_affiliation_strings":["Eli Lilly and Company, Lilly Seaport Innovation Center , , , ,"],"raw_orcid":"https://orcid.org/0000-0002-3518-0772","affiliations":[{"raw_affiliation_string":"Eli Lilly and Company, Lilly Seaport Innovation Center , , , ,","institution_ids":["https://openalex.org/I168537998"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5153098087","display_name":"Harmon Johnson","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I168537998","display_name":"Eli Lilly (United States)","ror":"https://ror.org/01qat3289","country_code":"US","type":"company","lineage":["https://openalex.org/I168537998"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Harmon Johnson","raw_affiliation_strings":["Eli Lilly and Company, Lilly Seaport Innovation Center , , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Eli Lilly and Company, Lilly Seaport Innovation Center , , , ,","institution_ids":["https://openalex.org/I168537998"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161470345","display_name":"Dylan Charland","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I168537998","display_name":"Eli Lilly (United States)","ror":"https://ror.org/01qat3289","country_code":"US","type":"company","lineage":["https://openalex.org/I168537998"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Dylan Charland","raw_affiliation_strings":["Eli Lilly and Company, Lilly Seaport Innovation Center , , , ,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Eli Lilly and Company, Lilly Seaport Innovation Center , , , ,","institution_ids":["https://openalex.org/I168537998"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5002338347","display_name":"Wu Jiang","orcid":"https://orcid.org/0000-0002-1873-178X","observed_orcids":["https://orcid.org/0000-0002-1873-178X"]},"institutions":[{"id":"https://openalex.org/I168537998","display_name":"Eli Lilly (United States)","ror":"https://ror.org/01qat3289","country_code":"US","type":"company","lineage":["https://openalex.org/I168537998"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Jiang Wu","raw_affiliation_strings":["Eli Lilly and Company, Lilly Seaport Innovation Center , , , ,"],"raw_orcid":"https://orcid.org/0009-0004-7067-8519","affiliations":[{"raw_affiliation_string":"Eli Lilly and Company, Lilly Seaport Innovation Center , , , ,","institution_ids":["https://openalex.org/I168537998"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5002338347","https://openalex.org/A5161455900"],"corresponding_institution_ids":["https://openalex.org/I168537998"],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"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/T10725","display_name":"RNA Interference and Gene Delivery","score":0.9771000146865845,"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":0.9771000146865845,"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/T10063","display_name":"Nanoparticle-Based Drug Delivery","score":0.011099999770522118,"subfield":{"id":"https://openalex.org/subfields/2502","display_name":"Biomaterials"},"field":{"id":"https://openalex.org/fields/25","display_name":"Materials Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T11460","display_name":"Analytical Methods in Pharmaceuticals","score":0.006500000134110451,"subfield":{"id":"https://openalex.org/subfields/1602","display_name":"Analytical Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7353000044822693},{"id":"https://openalex.org/C91881484","wikidata":"https://www.wikidata.org/wiki/Q191807","display_name":"Fluorescence","level":2,"score":0.6420000195503235},{"id":"https://openalex.org/C43617362","wikidata":"https://www.wikidata.org/wiki/Q170050","display_name":"Chromatography","level":1,"score":0.6044999957084656},{"id":"https://openalex.org/C67705224","wikidata":"https://www.wikidata.org/wiki/Q11053","display_name":"RNA","level":3,"score":0.5687000155448914},{"id":"https://openalex.org/C23531484","wikidata":"https://www.wikidata.org/wiki/Q3196863","display_name":"Calibration curve","level":3,"score":0.5608999729156494},{"id":"https://openalex.org/C155672457","wikidata":"https://www.wikidata.org/wiki/Q61231","display_name":"Nanoparticle","level":2,"score":0.5148000121116638},{"id":"https://openalex.org/C96618451","wikidata":"https://www.wikidata.org/wiki/Q3028008","display_name":"Dilution","level":2,"score":0.4221999943256378},{"id":"https://openalex.org/C102931765","wikidata":"https://www.wikidata.org/wiki/Q189673","display_name":"Dissociation (chemistry)","level":2,"score":0.4187000095844269},{"id":"https://openalex.org/C119128265","wikidata":"https://www.wikidata.org/wiki/Q900165","display_name":"Detection limit","level":2,"score":0.4156999886035919},{"id":"https://openalex.org/C74998103","wikidata":"https://www.wikidata.org/wiki/Q898254","display_name":"Dissociation constant","level":3,"score":0.39489999413490295},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.387800008058548},{"id":"https://openalex.org/C113196181","wikidata":"https://www.wikidata.org/wiki/Q485223","display_name":"Analytical Chemistry (journal)","level":2,"score":0.3659999966621399},{"id":"https://openalex.org/C105580179","wikidata":"https://www.wikidata.org/wiki/Q188928","display_name":"Messenger RNA","level":3,"score":0.34689998626708984},{"id":"https://openalex.org/C165838908","wikidata":"https://www.wikidata.org/wiki/Q736777","display_name":"Calibration","level":2,"score":0.3305000066757202},{"id":"https://openalex.org/C112190416","wikidata":"https://www.wikidata.org/wiki/Q2124450","display_name":"RNA extraction","level":4,"score":0.33009999990463257},{"id":"https://openalex.org/C129312508","wikidata":"https://www.wikidata.org/wiki/Q133686","display_name":"Oligonucleotide","level":3,"score":0.321399986743927},{"id":"https://openalex.org/C73090800","wikidata":"https://www.wikidata.org/wiki/Q6466869","display_name":"Label-free quantification","level":5,"score":0.3037000000476837},{"id":"https://openalex.org/C184112429","wikidata":"https://www.wikidata.org/wiki/Q476174","display_name":"Serial dilution","level":3,"score":0.296099990606308},{"id":"https://openalex.org/C2778576202","wikidata":"https://www.wikidata.org/wiki/Q2540164","display_name":"Sample preparation","level":2,"score":0.27559998631477356},{"id":"https://openalex.org/C10390740","wikidata":"https://www.wikidata.org/wiki/Q2282401","display_name":"Analyte","level":2,"score":0.27239999175071716},{"id":"https://openalex.org/C2994048982","wikidata":"https://www.wikidata.org/wiki/Q1768467","display_name":"Fluorescence spectrometry","level":3,"score":0.25920000672340393},{"id":"https://openalex.org/C162356407","wikidata":"https://www.wikidata.org/wiki/Q180809","display_name":"Mass spectrometry","level":2,"score":0.25609999895095825}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1021/acs.molpharmaceut.6c01077","doi":"https://doi.org/10.1021/acs.molpharmaceut.6c01077","is_oa":false,"landing_page_url":"https://doi.org/10.1021/acs.molpharmaceut.6c01077","pdf_url":null,"source":{"id":"https://openalex.org/S204562082","display_name":"Molecular Pharmaceutics","issn_l":"1543-8384","issn":["1543-8384","1543-8392"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-c","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Molecular Pharmaceutics","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":19,"referenced_works":["https://openalex.org/W2002830509","https://openalex.org/W3164967630","https://openalex.org/W4391322999","https://openalex.org/W4396534299","https://openalex.org/W4399917183","https://openalex.org/W4400356321","https://openalex.org/W4401334300","https://openalex.org/W4403827653","https://openalex.org/W4409048701","https://openalex.org/W4409387778","https://openalex.org/W4413448841","https://openalex.org/W4414162725","https://openalex.org/W4414512354","https://openalex.org/W4414579922","https://openalex.org/W4415895821","https://openalex.org/W7128385732","https://openalex.org/W7134285065","https://openalex.org/W7164521417","https://openalex.org/W7203819109"],"related_works":[],"abstract_inverted_index":{"Abstract":[0],"The":[1,62],"RiboGreen":[2],"fluorescence":[3,171],"assay":[4,45,65,107,126],"is":[5,219],"widely":[6],"utilized":[7],"to":[8,55,160,169,192,215],"determine":[9],"mRNA":[10,83],"encapsulation":[11],"efficiency":[12],"(EE":[13],"%)":[14],"in":[15,103,136,156,164],"lipid":[16,51],"nanoparticle":[17],"(LNP)":[18],"formulations":[19,54],"by":[20],"separately":[21],"quantifying":[22],"free":[23,105,125],"and":[24,34,49,72,85,227],"total":[25,63],"mRNA,":[26],"but":[27],"both":[28,47],"measurements":[29],"often":[30],"exhibit":[31],"high":[32],"variability":[33],"inconsistent":[35],"performance,":[36],"compromising":[37],"accurate":[38,210],"EE":[39,143,211,224],"%":[40,144,212,225],"measurement.":[41],"We":[42],"evaluated":[43],"each":[44],"using":[46,79],"LNP":[48],"targeted":[50],"nanoparticles":[52,80,180],"(tLNP)":[53],"identify":[56],"root":[57],"causes":[58],"of":[59,75,114,131,146,206],"poor":[60],"performance.":[61],"RNA":[64,106],"performed":[66],"acceptably,":[67],"with":[68,81,178,198],"%CV":[69,199],"below":[70],"13%":[71],"inter-run":[73],"recovery":[74,191],"92\u2212113%":[76],"as":[77,184],"assessed":[78],"known":[82],"concentration":[84],"different":[86],"ionizable":[87],"lipids,":[88],"confirming":[89],"complete":[90],"RNA\u2212lipid":[91],"dissociation":[92],"under":[93],"Triton":[94],"X-100":[95],"lysis.":[96],"Progressive":[97],"fluorescent":[98],"signal":[99],"decay":[100],"was":[101],"observed":[102],"the":[104,112,124,153,162,165,174,203],"during":[108],"prolonged":[109],"incubation,":[110],"highlighting":[111],"importance":[113],"an":[115],"optimal":[116],"time":[117],"window":[118],"for":[119,222,233],"plate":[120],"reading.":[121],"More":[122],"strikingly,":[123],"yielded":[127],"a":[128,185,229],"systematic":[129],"underestimation":[130],"over":[132],"30%":[133],"when":[134],"calibrated":[135],"conventional":[137],"Trizma-EDTA":[138],"(TE)":[139],"buffer,":[140],"inflating":[141],"apparent":[142],"irrespective":[145],"dilution":[147],"factor.":[148],"Parallelism":[149],"testing":[150],"revealed":[151],"that":[152],"calibration":[154,176,218],"curve":[155],"TE":[157,175],"buffer":[158,177],"failed":[159],"match":[161],"responses":[163],"sample":[166],"matrix,":[167],"attributable":[168],"nanoparticle-mediated":[170],"attenuation.":[172],"Substituting":[173],"empty":[179],"(LNPs":[181],"without":[182],"mRNA)":[183],"surrogate":[186],"matrix":[187],"restored":[188],"inter-day":[189],"spike-in":[190],"84\u2212102%":[193],"across":[194],"1\u221210%":[195],"spike":[196],"levels":[197],"\u2264":[200],"18%":[201],"at":[202],"lower":[204],"limit":[205],"quantitation":[207],"(LOQ),":[208],"enabling":[209],"reporting":[213],"up":[214],"99%.":[216],"Matrix-matched":[217],"therefore":[220],"essential":[221],"reliable":[223],"determination":[226],"represents":[228],"broadly":[230],"applicable":[231],"solution":[232],"method":[234],"qualification.":[235]},"counts_by_year":[],"updated_date":"2026-11-12T12:28:57.059296","created_date":"2026-11-12T00:00:00"}
