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The development of potent therapeutic regimens based on the RNA interference (RNAi) and clustered regularly interspaced short palindromic repeats (CRISPR-Cas) mechanisms will be described, which can be delivered by lentiviral vectors. These mechanisms attack different forms of the viral genome, the RNA and DNA, respectively, but both mechanisms act in a strictly sequence-specific manner. Early RNAi experiments demonstrated profound virus inhibition, but also indicated that viral escape is possible. Such therapy failure can be prevented by the design of a combinatorial RNAi attack on the virus and this gene therapy is currently being tested in a preclinical humanized mouse model. Recent CRISPR-Cas studies also document robust virus inhibition, but suggest a novel viral escape route that is induced by the cellular nonhomologous end joining DNA repair pathway, which is activated by CRISPR-Cas-induced DNA breaks. We will compare these two approaches for durable HIV-1 suppression and discuss the respective advantages and disadvantages. The potential for future clinical applications will be described.<\/jats:p>","DOI":"10.1042\/bst20160060","type":"journal-article","created":{"date-parts":[[2016,10,19]],"date-time":"2016-10-19T10:07:29Z","timestamp":1476871649000},"page":"1355-1365","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Attacking HIV-1 RNA versus DNA by sequence-specific approaches: RNAi versus CRISPR-Cas"],"prefix":"10.1042","volume":"44","author":[{"given":"Elena","family":"Herrera-Carrillo","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Berkhout","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2016,10,19]]},"reference":[{"key":"2021111720081523500_BST-2016-0060C1","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1002\/rmv.415","article-title":"Prospects for antiviral ribozymes and deoxyribozymes","volume":"14","author":"Peracchi","year":"2004","journal-title":"Rev. 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