{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:52:15Z","timestamp":1791348735790,"version":"4.3.1"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2017,6,7]],"date-time":"2017-06-07T00:00:00Z","timestamp":1496793600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:p>MicroRNA\u2010122 is an important host factor for the hepatitis C virus (HCV). Treatment with RG\u2010101, an <jats:italic toggle=\"yes\">N<\/jats:italic>\u2010acetylgalactosamine\u2010conjugated anti\u2010microRNA\u2010122 oligonucleotide, resulted in a significant viral load reduction in patients with chronic HCV infection. Here, we analyzed the effects of RG\u2010101 therapy on antiviral immunity. Thirty\u2010two chronic HCV patients infected with HCV genotypes 1, 3, and 4 received a single subcutaneous administration of RG\u2010101 at 2 mg\/kg (n = 14) or 4 mg\/kg (n = 14) or received a placebo (n = 2\/dosing group). Plasma and peripheral blood mononuclear cells were collected at multiple time points, and comprehensive immunological analyses were performed. Following RG\u2010101 administration, HCV RNA declined in all patients (mean decline at week 2, 3.27 log10 IU\/mL). At week 8 HCV RNA was undetectable in 15\/28 patients. Plasma interferon\u2010\u03b3\u2010induced protein 10 (IP\u201010) levels declined significantly upon dosing with RG\u2010101. Furthermore, the frequency of natural killer (NK) cells increased, the proportion of NK cells expressing activating receptors normalized, and NK cell interferon\u2010\u03b3 production decreased after RG\u2010101 dosing. Functional HCV\u2010specific interferon\u2010\u03b3 T\u2010cell responses did not significantly change in patients who had undetectable HCV RNA levels by week 8 post\u2013RG\u2010101 injection. No increase in the magnitude of HCV\u2010specific T\u2010cell responses was observed at later time points, including 3 patients who were HCV RNA\u2013negative 76 weeks postdosing. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Dosing with RG\u2010101 is associated with a restoration of NK\u2010cell proportions and a decrease of NK cells expressing activation receptors; however, the magnitude and functionality of <jats:italic toggle=\"yes\">ex vivo<\/jats:italic> HCV\u2010specific T\u2010cell responses did not increase following RG\u2010101 injection, suggesting that NK cells, but not HCV adaptive immunity, may contribute to HCV viral control following RG\u2010101 therapy. (H<jats:sc>epatology<\/jats:sc> 2017;66:57\u201368).<\/jats:p>","DOI":"10.1002\/hep.29148","type":"journal-article","created":{"date-parts":[[2017,3,11]],"date-time":"2017-03-11T08:59:01Z","timestamp":1489222741000},"page":"57-68","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":53,"title":["Immune phenotype and function of natural killer and T cells in chronic hepatitis C patients who received a single dose of anti\u2010MicroRNA\u2010122, RG\u2010101"],"prefix":"10.1097","volume":"66","author":[{"given":"Femke","family":"Stelma","sequence":"first","affiliation":[{"name":"Departments of Gastroenterology and Hepatology,Academic Medical Center,Amsterdam,The Netherlands"},{"name":"Experimental Immunology,Academic Medical Center,Amsterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meike H.","family":"van der Ree","sequence":"additional","affiliation":[{"name":"Departments of Gastroenterology and Hepatology,Academic Medical Center,Amsterdam,The Netherlands"},{"name":"Experimental Immunology,Academic Medical Center,Amsterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan J.","family":"Sinnige","sequence":"additional","affiliation":[{"name":"Experimental Immunology,Academic Medical Center,Amsterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Brown","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine and the Oxford NIHR BRC,University of Oxford,Oxford,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Swadling","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine and the Oxford NIHR BRC,University of Oxford,Oxford,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Marleen L.","family":"de Vree","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,University Medical Center Groningen,Groningen,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie B.","family":"Willemse","sequence":"additional","affiliation":[{"name":"Departments of Gastroenterology and Hepatology,Academic Medical Center,Amsterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"van der Valk","sequence":"additional","affiliation":[{"name":"Departments of Gastroenterology and Hepatology,Academic Medical Center,Amsterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Grint","sequence":"additional","affiliation":[{"name":"Regulus Therapeutics,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Neben","sequence":"additional","affiliation":[{"name":"Regulus Therapeutics,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine and the Oxford NIHR BRC,University of Oxford,Oxford,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Barnes","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine and the Oxford NIHR BRC,University of Oxford,Oxford,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeltje A.","family":"Kootstra","sequence":"additional","affiliation":[{"name":"Experimental Immunology,Academic Medical Center,Amsterdam,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik W.","family":"Reesink","sequence":"additional","affiliation":[{"name":"Departments of Gastroenterology and Hepatology,Academic Medical Center,Amsterdam,The 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