{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:50:48Z","timestamp":1790909448553,"version":"4.1.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"22","license":[{"start":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T00:00:00Z","timestamp":1605657600000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100006919","name":"Massachusetts Institute of Technology","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100006919","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["EB000244"],"award-info":[{"award-number":["EB000244"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["5T32DK007191-45"],"award-info":[{"award-number":["5T32DK007191-45"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005156","name":"Alexander von Humboldt-Stiftung","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100005156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["1P30AI094189"],"award-info":[{"award-number":["1P30AI094189"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,6,2]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Direct-acting antiviral (DAA) therapy is highly effective against hepatitis C virus (HCV). Despite this, the burden of chronic HCV remains high, particularly in populations for whom daily medications can be challenging. The generation of long-acting modes of DAA delivery could thus expand HCV treatment. We have developed a long-acting DAA system (LA-DAAS) that can support multigram-level drug depots of HCV DAAs and provide controlled release of those drugs over the course of weeks. We demonstrate initial safety and efficacy of the LA-DAAS in a swine model. Expanding the range of delivery options of DAAs to patients and healthcare providers will further efforts toward global elimination of HCV infection.<\/jats:p>","DOI":"10.1073\/pnas.2004746117","type":"journal-article","created":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T20:25:39Z","timestamp":1589833539000},"page":"11987-11994","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":25,"title":["Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine"],"prefix":"10.1073","volume":"117","author":[{"given":"Malvika","family":"Verma","sequence":"first","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Tata Center for Technology and Design, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline N.","family":"Chu","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A. F.","family":"Salama","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed T.","family":"Faiz","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feyisope","family":"Eweje","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Declan","family":"Gwynne","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Lopes","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Hess","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vance","family":"Soares","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Steiger","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115;"},{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"McManus","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Koeppen","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Hua","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Hayward","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy","family":"Collins","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddartha M.","family":"Tamang","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Ishida","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan B.","family":"Miller","sequence":"additional","affiliation":[{"name":"Sloan School of Management, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Katz","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander H.","family":"Slocum","sequence":"additional","affiliation":[{"name":"Tata Center for Technology and Design, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Sulkowski","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4255-0492","authenticated-orcid":false,"given":"Robert","family":"Langer","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Tata Center for Technology and Design, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Traverso","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Tata Center for Technology and Design, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;"},{"name":"Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,5,18]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29685"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.7326\/M16-2575"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.7326\/M18-1715"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31694-5"},{"key":"e_1_3_3_5_2","unstructured":"World Health Organization \u201cGlobal hepatitis report 2017\u201d (WHO Rep. World Health Organization Geneva Switzerland 2017)."},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1810477"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.7326\/M17-1876"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.7326\/M15-0406"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.106"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(18)30270-X"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29611"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26431"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.10.048"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra050100"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000510"},{"key":"e_1_3_3_16_2","unstructured":"Unitaid \u201cImpact story: Paving the way to hepatitis C elimination\u201d (Tech. Rep. Unitaid Geneva Switzerland 2018)."},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau6267"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgh-2018-001323"},{"key":"e_1_3_3_19_2","unstructured":"World Health Organization \u201cGuidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection\u201d (Tech. Rep. World Health Organization Geneva Switzerland 2018)."},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2019.04.912"},{"key":"e_1_3_3_21_2","unstructured":"ClinicalTrials.gov Digimeds to optimize adherence in patients with hepatitis C and increased risk for nonadherence (DASH). https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03164902. Accessed 8 July 2019."},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0921-5093(99)00294-4"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23258"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz166"},{"key":"e_1_3_3_25_2","unstructured":"World Health Organization \u201cPatient engagement\u201d (Technical Series on Safer Primary Care World Health Organization Geneva Switzerland 2016)."},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/admt.201800490"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aag2374"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.03.022"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2018.02.019"},{"key":"e_1_3_3_30_2","unstructured":"World Health Organization \u201cProgress report on access to hepatitis C treatment: Focus on overcoming barriers in low-and middle-income countries March 2018\u201d (Tech. Rep. WHO\/CDS\/HIV\/18.4 World Health Organization Geneva Switzerland 2018)."},{"key":"e_1_3_3_31_2","unstructured":"M. E. Tucker FDA approves \u201cgame changer\u201d hepatitis C drug sofosbuvir. Medscape Medical News 7 June 2019. https:\/\/www.medscape.com\/viewarticle\/817371. Accessed 8 July 2019."},{"key":"e_1_3_3_32_2","unstructured":"Hepatitis C Online Ledipasvir-sofosbuvir (Harvoni). https:\/\/www.hepatitisc.uw.edu\/page\/treatment\/drugs\/ledipasvir-sofosbuvir. Accessed 7 June 2019."},{"key":"e_1_3_3_33_2","first-page":"256","article-title":"Ledipasvir\/sofosbuvir (Harvoni): Improving options for hepatitis C virus infection","volume":"40","author":"Gritsenko D.","year":"2015","unstructured":"D. Gritsenko, G. Hughes, Ledipasvir\/sofosbuvir (Harvoni): Improving options for hepatitis C virus infection. P&T 40, 256\u2013276 (2015).","journal-title":"P&T"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27726"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-009-9923-1"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2015.04.069"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau8581"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.3144\/expresspolymlett.2014.88"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.polymdegradstab.2010.09.007"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0261-7"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02587-17"},{"key":"e_1_3_3_42_2","unstructured":"J. A. Quinlan Gastric balloon cost insurance & discounts. Bariatric Surgery Source. https:\/\/www.bariatric-surgery-source.com\/gastric-balloon-cost.html. Accessed 4 April 2019."},{"key":"e_1_3_3_43_2","unstructured":"AASLD-IDSA Recommendations for testing managing and treating hepatitis C. https:\/\/www.hcvguidelines.org. Accessed 31 May 2019."},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02294-6"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01529-09"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22403"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169401"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-307772"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1405158"},{"key":"e_1_3_3_50_2","unstructured":"Bureau of Labor Statistics Consumer price index. https:\/\/www.bls.gov\/cpi\/. Accessed 12 March 2019."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2004746117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2004746117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T07:13:27Z","timestamp":1649834007000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2004746117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,18]]},"references-count":50,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2020,6,2]]}},"alternative-id":["10.1073\/pnas.2004746117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2004746117","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,18]]},"assertion":[{"value":"2020-05-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}