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Science 29 June 2007:
Vol. 316. no. 5833, pp. 1912 - 1915
DOI: 10.1126/science.1141453

Reports

HIV-1 Proviral DNA Excision Using an Evolved Recombinase

Indrani Sarkar,1* Ilona Hauber,2* Joachim Hauber,2{dagger} Frank Buchholz1{dagger}

HIV-1 integrates into the host chromosome and persists as a provirus flanked by long terminal repeats (LTRs). To date, treatment regimens primarily target the virus enzymes or virus-cell fusion, but not the integrated provirus. We report here the substrate-linked protein evolution of a tailored recombinase that recognizes an asymmetric sequence within an HIV-1 LTR. This evolved recombinase efficiently excised integrated HIV proviral DNA from the genome of infected cells. Although a long way from use in the clinic, we speculate that this type of technology might be adapted in future antiretroviral therapies, among other possible uses.

1 Max-Planck-Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307 Dresden, Germany.
2 Heinrich-Pette-Institute for Experimental Virology and Immunology, Martinistrasse 52, D-20251 Hamburg, Germany.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: joachim.hauber{at}hpi.uni-hamburg.de (J.H.); buchholz{at}mpi-cbg.de (F.B.)

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