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Kontakte
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Publikationen
* joint first author
# joint corresponding author
2016
Janet Karpinski, Ilona Hauber, Jan Chemnitz, Carola Schäfer, Maciej Paszkowski-Rogacz, Debojyoti Chakraborty, Niklas Beschorner, Helga Hofmann-Sieber, Ulrike C Lange, Adam Grundhoff, Karl Hackmann, Evelin Schrock, Josephine Abi-Ghanem, Maria Teresa Pisabarro, Vineeth Surendranath, Axel Schambach, Christoph Lindner, Jan van Lunzen, Joachim Hauber, Frank Buchholz Directed evolution of a recombinase that excises the provirus of most HIV-1 primary isolates with high specificity. Nat Biotechnol, 34(4) 401-409 (2016) DOI
Current combination antiretroviral therapies (cART) efficiently suppress HIV-1 reproduction in humans, but the virus persists as integrated proviral reservoirs in small numbers of cells. To generate an antiviral agent capable of eradicating the provirus from infected cells, we employed 145 cycles of substrate-linked directed evolution to evolve a recombinase (Brec1) that site-specifically recognizes a 34-bp sequence present in the long terminal repeats (LTRs) of the majority of the clinically relevant HIV-1 strains and subtypes. Brec1 efficiently, precisely and safely removes the integrated provirus from infected cells and is efficacious on clinical HIV-1 isolates in vitro and in vivo, including in mice humanized with patient-derived cells. Our data suggest that Brec1 has potential for clinical application as a curative HIV-1 therapy.
