{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T03:16:44Z","timestamp":1762917404560},"reference-count":0,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[1993,2,1]],"date-time":"1993-02-01T00:00:00Z","timestamp":728524800000},"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":[[1993,2]]},"abstract":"<jats:p>Papillomaviruses induce benign proliferative lesions, such as genital warts, in humans. The E2 gene product is thought to play a major role in the regulation of viral transcription and DNA replication and may represent a rational target for an antisense oligonucleotide drug action. Phosphorothioate oligonucleotides complementary to E2 mRNAs were synthesized and tested in a series of in vitro bovine papillomavirus (BPV) and human papillomavirus (HPV) models for the ability to inhibit E2 transactivation and virus-induced focus formation. The most active BPV-specific compounds were complementary to the mRNA cap region (ISIS 1751), the translation initiation region for the full-length E2 transactivator (ISIS 1753), and the translation initiation region for the E2 transrepressor mRNA (ISIS 1755). ISIS 1751 and ISIS 1753 were found to reduce E2-dependent transactivation and viral focus formation in a sequence-specific and concentration-dependent manner. ISIS 1755 increased E2 transactivation in a dose-dependent manner but had no effect on focus formation. Oligonucleotides with a chain length of 20 residues had optimal activity in the E2 transactivation assay. On the basis of the above observations, ISIS 2105, a 20-residue phosphorothioate oligonucleotide targeted to the translation initiation of both HPV type 6 (HPV-6) and HPV-11 E2 mRNA, was designed and shown to inhibit E2-dependent transactivation by HPV-11 E2 expressed from a surrogate promoter. These observations support the rationale of E2 as a target for antiviral therapy against papillomavirus infections and specifically identify ISIS 2105 as a candidate antisense oligonucleotide for the treatment of genital warts induced by HPV-6 and HPV-11.<\/jats:p>","DOI":"10.1128\/aac.37.2.171","type":"journal-article","created":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T00:05:50Z","timestamp":1340841950000},"page":"171-177","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":79,"title":["In vitro evaluation of phosphorothioate oligonucleotides targeted to the E2 mRNA of papillomavirus: potential treatment for genital warts"],"prefix":"10.1128","volume":"37","author":[{"given":"L M","family":"Cowsert","sequence":"first","affiliation":[{"name":"ISIS Pharmaceuticals, Carlsbad, California 92008."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M C","family":"Fox","sequence":"additional","affiliation":[{"name":"ISIS Pharmaceuticals, Carlsbad, California 92008."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Zon","sequence":"additional","affiliation":[{"name":"ISIS Pharmaceuticals, Carlsbad, California 92008."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C K","family":"Mirabelli","sequence":"additional","affiliation":[{"name":"ISIS Pharmaceuticals, Carlsbad, California 92008."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.37.2.171","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.37.2.171","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T15:33:03Z","timestamp":1645457583000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.37.2.171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,2]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1993,2]]}},"alternative-id":["10.1128\/AAC.37.2.171"],"URL":"https:\/\/doi.org\/10.1128\/aac.37.2.171","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,2]]},"assertion":[{"value":"1993-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}