{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:41:41Z","timestamp":1777452101681,"version":"3.51.4"},"reference-count":17,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>RNA interference (RNAi) provides an attractive tool to modulate biological systems, and ultimately, to treat human diseases. We describe early results from a Phase Ib, first-in-human safety and tolerability study of an RNAi-based therapy, NUC B1000, among patients with mild to moderate chronic HBV.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Three subjects received a single 5 mg DNA dose of NUC B1000 as part of a planned dose escalation study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All participants reported pharyngitis, chills, myalgia and fever approximately 4\u20137 h after dosing. All subjects were asymptomatic after a single antipyretic dose with no symptom recurrences. Measurements of interferon (IFN)-\u03b1 and -\u03b3, interleukin (IL)-10, 12 18, 8 and 6, and tumour necrosis factor-\u03b1 performed before and after dosing revealed cytokine increases before study drug administration. After drug administration, IFN-\u03b3 and IL-10 increased in two patients; IL-8 increased in one. Most increases returned to pretreatment levels within 1 week. Two patients were subsequently successfully treated with entecavir indicating that NUC B1000 does not compromise subsequent antiviral therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Thus far, NUC B1000 appears safe and well-tolerated; safety and efficacy studies across a larger, more diverse patient spectrum using increasing doses are needed to determine its appropriate role in the antiviral armamentarium.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp1798","type":"journal-article","created":{"date-parts":[[2011,5,17]],"date-time":"2011-05-17T13:54:43Z","timestamp":1305640483000},"page":"547-554","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":27,"title":["RNA Interference and Its Potential Applications to Chronic HBV Treatment: Results of a Phase I Safety and Tolerability Study"],"prefix":"10.1177","volume":"16","author":[{"given":"Robert G","family":"Gish","sequence":"first","affiliation":[{"name":"Center for Hepatobiliary Disease and Abdominal Transplantation, UCSD Medical Center, San Diego, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Satishchandran","sequence":"additional","affiliation":[{"name":"Center for Biopharmaceutical Research, North Dakota State University, Fargo, ND, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Young","sequence":"additional","affiliation":[{"name":"MDY-Associates LLC, Devon, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Pachuk","sequence":"additional","affiliation":[{"name":"BioTx Division, Pfizer Research Technology Center, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2011,5,1]]},"reference":[{"key":"bibr1-IMP1798","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2009.06.001"},{"key":"bibr2-IMP1798","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2009.06.002"},{"key":"bibr3-IMP1798","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra045004"},{"key":"bibr4-IMP1798","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90529-Y"},{"key":"bibr5-IMP1798","doi-asserted-by":"publisher","DOI":"10.1038\/35888"},{"key":"bibr6-IMP1798","doi-asserted-by":"publisher","DOI":"10.1038\/nature04791"},{"key":"bibr7-IMP1798","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(96)80061-X"},{"key":"bibr8-IMP1798","doi-asserted-by":"publisher","DOI":"10.2307\/3869076"},{"key":"bibr9-IMP1798","unstructured":"Recombinant DNA Advisory Committee (RAC). 2006 Past RAC meetings. Office of Biotechnology Activities. 2006. National Institutes of Health. (Updated 27 October 2010. Accessed 28 August 2009.) Available from http:\/\/oba.od.nih.gov\/rdna\/rac_past_meeting_2006_webcasts.html#dec06, http:\/\/oba.od.nih.gov\/rdna_rac\/rac_past_meetings_2000.html#RAC2006."},{"key":"bibr10-IMP1798","doi-asserted-by":"publisher","DOI":"10.1126\/science.1068836"},{"key":"bibr11-IMP1798","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1339"},{"key":"bibr12-IMP1798","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21513"},{"key":"bibr13-IMP1798","unstructured":"US Food and Drug Administration, Department of Health and Human Services. Adverse event reporting system (AERS). (Updated 20 August 2009. Accessed 25 October 2010.) Available from http:\/\/www.fda.gov\/Drugs\/GuidanceComplianceRegulatoryInformation\/Surveillance\/AdverseDrugEffects\/default.htm."},{"key":"bibr14-IMP1798","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.03.013"},{"key":"bibr15-IMP1798","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21844"},{"key":"bibr16-IMP1798","doi-asserted-by":"publisher","DOI":"10.1038\/nm1589"},{"key":"bibr17-IMP1798","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1206"}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP1798","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP1798","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:50:06Z","timestamp":1777380606000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3851\/IMP1798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5]]},"references-count":17,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2011,5]]}},"alternative-id":["10.3851\/IMP1798"],"URL":"https:\/\/doi.org\/10.3851\/imp1798","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,5]]}}}