{"id":"https://openalex.org/W1995956587","doi":"https://doi.org/10.1002/jgm.696","title":"Exploring polyethylenimine\u2010mediated DNA transfection and the proton sponge hypothesis","display_name":"Exploring polyethylenimine\u2010mediated DNA transfection and the proton sponge hypothesis","publication_year":2004,"publication_date":"2004-11-15","ids":{"openalex":"https://openalex.org/W1995956587","doi":"https://doi.org/10.1002/jgm.696","mag":"1995956587","pmid":"https://pubmed.ncbi.nlm.nih.gov/15543529"},"language":"en","primary_location":{"id":"doi:10.1002/jgm.696","doi":"https://doi.org/10.1002/jgm.696","is_oa":false,"landing_page_url":"https://doi.org/10.1002/jgm.696","pdf_url":null,"source":{"id":"https://openalex.org/S91057606","display_name":"The Journal of Gene Medicine","issn_l":"1099-498X","issn":["1099-498X","1521-2254"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-d","jufo-1","ki-jl-1","medline","norway-1","poland-40","russia-white-list-2"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journal of Gene Medicine","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"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/A5077685566","display_name":"Akin Akinc","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I63966007","display_name":"Massachusetts Institute of Technology","ror":"https://ror.org/042nb2s44","country_code":"US","type":"education","lineage":["https://openalex.org/I63966007"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Akin Akinc","raw_affiliation_strings":["Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA","institution_ids":["https://openalex.org/I63966007"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5061909087","display_name":"Mini Thomas","orcid":"https://orcid.org/0009-0006-2328-4191","observed_orcids":["https://orcid.org/0009-0006-2328-4191"]},"institutions":[{"id":"https://openalex.org/I63966007","display_name":"Massachusetts Institute of Technology","ror":"https://ror.org/042nb2s44","country_code":"US","type":"education","lineage":["https://openalex.org/I63966007"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mini Thomas","raw_affiliation_strings":["Department of Chemistry and Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry and Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA","institution_ids":["https://openalex.org/I63966007"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5023002381","display_name":"Alexander M. Klibanov","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I63966007","display_name":"Massachusetts Institute of Technology","ror":"https://ror.org/042nb2s44","country_code":"US","type":"education","lineage":["https://openalex.org/I63966007"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Alexander M. Klibanov","raw_affiliation_strings":["Department of Chemistry and Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry and Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA","institution_ids":["https://openalex.org/I63966007"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5042597057","display_name":"R\u00f3bert Langer","orcid":"https://orcid.org/0000-0003-4255-0492","observed_orcids":["https://orcid.org/0000-0003-4255-0492","https://orcid.org/0000-0001-5746-9940"]},"institutions":[{"id":"https://openalex.org/I63966007","display_name":"Massachusetts Institute of Technology","ror":"https://ror.org/042nb2s44","country_code":"US","type":"education","lineage":["https://openalex.org/I63966007"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Robert Langer","raw_affiliation_strings":["Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA","institution_ids":["https://openalex.org/I63966007"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5042597057"],"corresponding_institution_ids":["https://openalex.org/I63966007"],"apc_list":{"value":4480,"currency":"USD","value_usd":4480},"apc_paid":null,"fwci":6.6399,"has_fulltext":false,"cited_by_count":1363,"citation_normalized_percentile":{"value":0.9835459,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":99,"max":100},"biblio":{"volume":"7","issue":"5","first_page":"657","last_page":"663"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10725","display_name":"RNA Interference and Gene Delivery","score":0.9994999766349792,"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":0.9994999766349792,"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":0.00019999999494757503,"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/T11686","display_name":"Dendrimers and Hyperbranched Polymers","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2507","display_name":"Polymers and Plastics"},"field":{"id":"https://openalex.org/fields/25","display_name":"Materials Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/polyethylenimine","display_name":"polyethyleneimine","score":1.0},{"id":"https://openalex.org/keywords/dna-transfection","display_name":"DNA transfection","score":0.9729999899864197},{"id":"https://openalex.org/keywords/lysosome-escape","display_name":"lysosomal escape","score":0.609000027179718},{"id":"https://openalex.org/keywords/endosomal-ph","display_name":"endosomal pH","score":0.8230000138282776},{"id":"https://openalex.org/keywords/bafilomycin-a1","display_name":"bafilomycin A1","score":0.8539999723434448},{"id":"https://openalex.org/keywords/chloroquine","display_name":"chloroquine","score":0.9900000095367432},{"id":"https://openalex.org/keywords/cellular-uptake","display_name":"cellular uptake","score":0.7870000004768372},{"id":"https://openalex.org/keywords/vector-stability","display_name":"vector stability","score":0.5759999752044678},{"id":"https://openalex.org/keywords/dna-binding-affinity","display_name":"DNA binding affinity","score":0.6190000176429749},{"id":"https://openalex.org/keywords/polylysine","display_name":"polylysine","score":0.8740000128746033},{"id":"https://openalex.org/keywords/transfection-efficiency","display_name":"transfection efficiency","score":0.5809999704360962}],"concepts":[{"id":"https://openalex.org/C2775925850","wikidata":"https://www.wikidata.org/wiki/Q418697","display_name":"Polyethylenimine","level":4,"score":0.9523051977157593},{"id":"https://openalex.org/C54009773","wikidata":"https://www.wikidata.org/wiki/Q1429031","display_name":"Transfection","level":3,"score":0.9005171060562134},{"id":"https://openalex.org/C2777722557","wikidata":"https://www.wikidata.org/wiki/Q4841341","display_name":"Bafilomycin","level":4,"score":0.6639370918273926},{"id":"https://openalex.org/C12554922","wikidata":"https://www.wikidata.org/wiki/Q7100","display_name":"Biophysics","level":1,"score":0.602436900138855},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5909006595611572},{"id":"https://openalex.org/C2780075363","wikidata":"https://www.wikidata.org/wiki/Q650157","display_name":"Polylysine","level":2,"score":0.48424479365348816},{"id":"https://openalex.org/C190062978","wikidata":"https://www.wikidata.org/wiki/Q79899","display_name":"Cytoplasm","level":2,"score":0.47452059388160706},{"id":"https://openalex.org/C102747710","wikidata":"https://www.wikidata.org/wiki/Q824237","display_name":"Endosome","level":3,"score":0.4620809555053711},{"id":"https://openalex.org/C135983454","wikidata":"https://www.wikidata.org/wiki/Q2790163","display_name":"Gene delivery","level":4,"score":0.4327440559864044},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.4214341640472412},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.33124840259552},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.23816567659378052},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.185108482837677},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.07463467121124268},{"id":"https://openalex.org/C203522944","wikidata":"https://www.wikidata.org/wiki/Q288322","display_name":"Autophagy","level":3,"score":0.0},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.0}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000900","descriptor_name":"Anti-Bacterial Agents","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D002522","descriptor_name":"Chlorocebus aethiops","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002738","descriptor_name":"Chloroquine","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D003593","descriptor_name":"Cytoplasm","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D004247","descriptor_name":"DNA","qualifier_ui":"Q000008","qualifier_name":"administration & dosage","is_major_topic":true},{"descriptor_ui":"D005822","descriptor_name":"Genetic Vectors","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D006863","descriptor_name":"Hydrogen-Ion Concentration","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008156","descriptor_name":"Luciferases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D011094","descriptor_name":"Polyethyleneimine","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":true},{"descriptor_ui":"D011094","descriptor_name":"Polyethyleneimine","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D011107","descriptor_name":"Polylysine","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D011108","descriptor_name":"Polymers","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D011992","descriptor_name":"Endosomes","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D018014","descriptor_name":"Gene Transfer Techniques","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D018942","descriptor_name":"Macrolides","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D019556","descriptor_name":"COS Cells","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D054328","descriptor_name":"Proton Pump Inhibitors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1002/jgm.696","doi":"https://doi.org/10.1002/jgm.696","is_oa":false,"landing_page_url":"https://doi.org/10.1002/jgm.696","pdf_url":null,"source":{"id":"https://openalex.org/S91057606","display_name":"The Journal of Gene Medicine","issn_l":"1099-498X","issn":["1099-498X","1521-2254"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-d","jufo-1","ki-jl-1","medline","norway-1","poland-40","russia-white-list-2"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journal of Gene Medicine","raw_type":"journal-article"},{"id":"pmid:15543529","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/15543529","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":"The journal of gene medicine","raw_type":"Comparative Study"}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G4132846725","display_name":null,"funder_award_id":"EB00244","funder_id":"https://openalex.org/F4320337363","funder_display_name":"National Institute of Biomedical Imaging and Bioengineering"}],"funders":[{"id":"https://openalex.org/F4320306076","display_name":"National Science Foundation","ror":"https://ror.org/021nxhr62"},{"id":"https://openalex.org/F4320337363","display_name":"National Institute of Biomedical Imaging and Bioengineering","ror":"https://ror.org/00372qc85"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":36,"referenced_works":["https://openalex.org/W1529220262","https://openalex.org/W1538490497","https://openalex.org/W1541488575","https://openalex.org/W1966390198","https://openalex.org/W1967078049","https://openalex.org/W1981728824","https://openalex.org/W1987992257","https://openalex.org/W1994354502","https://openalex.org/W1999901349","https://openalex.org/W2002122821","https://openalex.org/W2010655741","https://openalex.org/W2012665920","https://openalex.org/W2012889187","https://openalex.org/W2013841789","https://openalex.org/W2020412719","https://openalex.org/W2022576626","https://openalex.org/W2023532191","https://openalex.org/W2025636757","https://openalex.org/W2026448356","https://openalex.org/W2026606185","https://openalex.org/W2026915678","https://openalex.org/W2030955277","https://openalex.org/W2035501441","https://openalex.org/W2057576065","https://openalex.org/W2062314015","https://openalex.org/W2071053001","https://openalex.org/W2078526525","https://openalex.org/W2090211284","https://openalex.org/W2092447252","https://openalex.org/W2107929771","https://openalex.org/W2136634346","https://openalex.org/W2142987628","https://openalex.org/W2151142281","https://openalex.org/W2160656343","https://openalex.org/W2165451824","https://openalex.org/W4292328694"],"related_works":["https://openalex.org/W2025636757","https://openalex.org/W1985523341","https://openalex.org/W7097071732","https://openalex.org/W4236947624","https://openalex.org/W7097549984","https://openalex.org/W3021012332","https://openalex.org/W2010655741","https://openalex.org/W4410958074","https://openalex.org/W3213070814","https://openalex.org/W2352254145"],"abstract_inverted_index":{"BACKGROUND:":[0],"The":[1,55,166,283],"relatively":[2],"high":[3],"transfection":[4,73,78,130,146,162,232,276,298],"efficiency":[5,131,147,163],"of":[6,34,42,48,57,88,98,120,132,138,148,164,171,207,223,234,244,278,300],"polyethylenimine":[7],"(PEI)":[8],"vectors":[9,89,173,211,302],"has":[10],"been":[11],"hypothesized":[12],"to":[13,16,19,22,26,37,66,77,107,182,214,240,305,309],"be":[14,215],"due":[15,239,304],"their":[17,306],"ability":[18,308],"avoid":[20,180,310],"trafficking":[21,181],"degradative":[23],"lysosomes.":[24,184,312],"According":[25],"the":[27,31,46,49,52,71,80,110,118,129,145,161,229,235,253,274,279,289,297],"proton":[28,111,125,290],"sponge":[29,112,291],"hypothesis,":[30],"buffering":[32],"capacity":[33],"PEI":[35,99,133,172,225,301],"leads":[36],"osmotic":[38],"swelling":[39],"and":[40,86,100,117,151,199,209,217,293],"rupture":[41],"endosomes,":[43],"resulting":[44],"in":[45,70,231],"release":[47],"vector":[50,268],"into":[51],"cytoplasm.":[53],"METHODS:":[54],"mechanism":[56],"PEI-mediated":[58],"DNA":[59,260],"transfer":[60],"was":[61,174,270],"investigated":[62],"using":[63],"quantitative":[64],"methods":[65],"study":[67],"individual":[68],"steps":[69],"overall":[72],"process.":[74],"In":[75,155],"addition":[76],"efficiency,":[79],"cellular":[81,245],"uptake,":[82],"local":[83],"pH":[84,169,188],"environment,":[85],"stability":[87],"were":[90,105,190,212],"analyzed.":[91],"N-Quaternized":[92],"(and":[93],"therefore":[94],"non-proton":[95],"sponge)":[96],"versions":[97],"specific":[101],"cell":[102],"function":[103],"inhibitors":[104],"used":[106],"further":[108],"probe":[109],"hypothesis.":[113],"RESULTS:":[114],"Both":[115],"N-quaternization":[116],"use":[119],"bafilomycin":[121],"A1":[122],"(a":[123],"vacuolar":[124],"pump":[126],"inhibitor)":[127],"reduced":[128,275],"by":[134,153],"approximately":[135],"two":[136],"orders":[137],"magnitude.":[139],"Chloroquine,":[140],"which":[141],"buffers":[142],"lysosomes,":[143],"enhanced":[144],"N-quaternized":[149,236,257,280],"PEIs":[150,237,258],"polylysine":[152,200],"2-3-fold.":[154],"contrast,":[156],"chloroquine":[157],"did":[158],"not":[159,271],"improve":[160],"PEI.":[165],"measured":[167],"average":[168,187],"environment":[170],"6.1,":[175],"indicating":[176,227],"that":[177,222,228,252,266,296],"they":[178],"successfully":[179],"acidic":[183,311],"Significantly":[185],"lower":[186],"environments":[189],"observed":[191],"for":[192,273],"permethyl-PEI":[193,208],"(pH":[194,197,201],"5.4),":[195],"perethyl-PEI":[196,210],"5.1),":[198],"4.6)":[202],"vectors.":[203],"Cellular":[204],"uptake":[205],"levels":[206],"found":[213],"20":[216],"90%":[218],"higher,":[219],"respectively,":[220],"than":[221,263],"parent":[224],"vectors,":[226],"reduction":[230],"activity":[233,277,299],"is":[238,303],"a":[241],"barrier":[242],"downstream":[243],"uptake.":[246],"A":[247],"polycation/DNA-binding":[248],"affinity":[249],"assessment":[250],"showed":[251],"more":[254],"charge":[255],"dense":[256],"bind":[259],"less":[261],"tightly":[262],"PEI,":[264],"demonstrating":[265],"poor":[267],"unpackaging":[269],"responsible":[272],"PEIs.":[281],"CONCLUSIONS:":[282],"results":[284],"obtained":[285],"are":[286],"consistent":[287],"with":[288],"hypothesis":[292],"strongly":[294],"suggest":[295],"unique":[307]},"counts_by_year":[{"year":2026,"cited_by_count":28},{"year":2025,"cited_by_count":35},{"year":2024,"cited_by_count":49},{"year":2023,"cited_by_count":40},{"year":2022,"cited_by_count":52},{"year":2021,"cited_by_count":66},{"year":2020,"cited_by_count":54},{"year":2019,"cited_by_count":59},{"year":2018,"cited_by_count":64},{"year":2017,"cited_by_count":89},{"year":2016,"cited_by_count":87},{"year":2015,"cited_by_count":79},{"year":2014,"cited_by_count":88},{"year":2013,"cited_by_count":99},{"year":2012,"cited_by_count":99}],"updated_date":"2026-11-12T12:28:57.059296","created_date":"2016-06-24T00:00:00"}