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We are exploiting one of the four retroviral enzymes, the ribonuclease H, RNase H, as a novel approach for a microbicide. It is the only enzyme of HIV not yet targeted by antiretroviral therapy. The enzyme is linked to the reverse transcriptase (RT) and hydrolyzes the RNA moiety of RNA\u2013DNA hybrids. The RNase H is located inside virus particles and normally functions during viral replication inside cells. Here we show that activating the RNase H prematurely inside the virus particles destroys the viral genome and abrogates viral infectivity. The antiviral compound consists of a synthetic oligodeoxynucleotide (ODN), which creates an artificial RNA\u2013DNA hybrid substrate for the RNase H inside the particle. The compound was analyzed in mouse models including humanized SCID mice and the vagina of mice. Infection was reduced up to 1000-fold or could be completely prevented. The compound is suitable as microbicide or to prevent mother-to-child transmission.<\/jats:p>","DOI":"10.1089\/aid.2012.0067","type":"journal-article","created":{"date-parts":[[2012,8,29]],"date-time":"2012-08-29T11:45:44Z","timestamp":1346240744000},"page":"1397-1403","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Premature Activation of the HIV RNase H Drives the Virus into Suicide: A Novel Microbicide?"],"prefix":"10.1177","volume":"28","author":[{"given":"Felix","family":"Broecker","sequence":"first","affiliation":[{"name":"University of Zurich","place":["Switzerland"]},{"name":"Max Planck Institute for Molecular Genetics","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karsten","family":"Andrae","sequence":"additional","affiliation":[{"name":"Zuse-Institut Berlin","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Moelling","sequence":"additional","affiliation":[{"name":"University of Zurich","place":["Switzerland"]},{"name":"Max Planck Institute for Molecular Genetics","place":["Germany"]},{"name":"Heinrich Pette Institute","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2012,11,1]]},"reference":[{"key":"e_1_3_3_2_2","volume-title":"Retroviruses","author":"Coffin JM","year":"1997","unstructured":"Coffin JM, , Hughes SH. 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