{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:48:40Z","timestamp":1791413320553,"version":"4.3.3"},"reference-count":13,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T00:00:00Z","timestamp":1414800000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Two identical single-ascending-dose studies evaluated the safety and pharmacokinetics (PK) of AVI-6002 and AVI-6003, two experimental combinations of phosphorodiamidate morpholino oligomers with positive charges (PMO\n            <jats:italic>plus<\/jats:italic>\n            ) that target viral mRNA encoding Ebola virus and Marburg virus proteins, respectively. Both AVI-6002 and AVI-6003 were found to suppress disease in virus-infected nonhuman primates in previous studies. AVI-6002 (a combination of AVI-7537 and AVI-7539) or AVI-6003 (a combination of AVI-7287 and AVI-7288) were administered as sequential intravenous (i.v.) infusions of a 1:1 fixed dose ratio of the two subcomponents. In each study, 30 healthy male and female subjects between 18 and 50 years of age were enrolled in six-dose escalation cohorts of five subjects each and received a single i.v. infusion of active study drug (0.005, 0.05, 0.5, 1.5, 3, and 4.5 mg\/kg per component) or placebo in a 4:1 ratio. Both AVI-6002 and AVI-6003 were safe and well tolerated at the doses studied. A maximum tolerated dose was not observed in either study. The four chemically similar PMO\n            <jats:italic>plus<\/jats:italic>\n            components exhibited generally similar PK profiles. The mean peak plasma concentration and area under the concentration-time curve values of the four components exhibited dose-proportional PK. The estimated plasma half-life of all four components was 2 to 5 h. The safety of the two combinations and the PK of the four components were similar, regardless of the target RNA sequence.\n          <\/jats:p>","DOI":"10.1128\/aac.03442-14","type":"journal-article","created":{"date-parts":[[2014,8,26]],"date-time":"2014-08-26T06:40:17Z","timestamp":1409035217000},"page":"6639-6647","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":77,"title":["Safety and Pharmacokinetic Profiles of Phosphorodiamidate Morpholino Oligomers with Activity against Ebola Virus and Marburg Virus: Results of Two Single-Ascending-Dose Studies"],"prefix":"10.1128","volume":"58","author":[{"given":"Alison E.","family":"Heald","sequence":"first","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick L.","family":"Iversen","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA"},{"name":"Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay B.","family":"Saoud","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sazani","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay S.","family":"Charleston","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Axtelle","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Wong","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Smith","sequence":"additional","affiliation":[{"name":"New Orleans Center for Clinical Research-Knoxville, Knoxville, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apinya","family":"Vutikullird","sequence":"additional","affiliation":[{"name":"West Coast Clinical Trials, Cypress, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Kaye","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001546"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.2217\/fvl.11.79"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cll.2009.12.001"},{"key":"e_1_3_2_5_2","volume-title":"Harrison's principles of internal medicine","author":"Fauci A","year":"2008","unstructured":"FauciABraunwaldEKasperDHauserSLongoDHamesonJLoscalzoJ. 2008. 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U.S. Centers for Disease Control and Prevention, Atlanta, GA. http:\/\/www.bt.cdc.gov\/agent\/agentlist-category.asp."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/v4112806"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2202"},{"key":"e_1_3_2_13_2","volume-title":"Guidance for industry: toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials","author":"U.S. Department of Health and Human Services\/U.S. Food and Drug Administration Center for Biologics Evaluation and Research","year":"2007","unstructured":"U.S. Department of Health and Human Services\/U.S. Food and Drug Administration Center for Biologics Evaluation and Research. 2007. Guidance for industry: toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials. 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