HIV-1 proviral DNA excision using an evolved recombinase.
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.
Sarkar
Indrani
I
Max-Planck-Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307 Dresden, Germany.
Hauber
Ilona
I
Hauber
Joachim
J
Buchholz
Frank
F
D000595:Amino Acid Sequence; D001483:Base Sequence; D032621:DNA Shuffling; D004279:DNA, Viral / Q000378:metabolism*; D019020:Directed Molecular Evolution; D004926:Escherichia coli / Q000235:genetics; D015723:Gene Library; D015894:Genome, Human; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D019426:Integrases / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D011533:Proviruses / Q000378:metabolism; D011995:Recombination, Genetic; D016662:Virus Integration
D004279:DNA, Viral; C045073:Cre recombinase; D019426:Integrases