HIV-1 Proviral DNA Excision Using an Evolved Recombinase

• Published in: Science (American Association for the Advancement of Science) Vol. 316; no. 5833; pp. 1912 - 1915
• Main Authors: Sarkar, Indrani, Hauber, Ilona, Hauber, Joachim, Buchholz, Frank
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 29.06.2007; The American Association for the Advancement of Science
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; Directed Molecular Evolution; DNA Shuffling; DNA, Viral - metabolism; Enzymes; Escherichia coli - genetics; Fundamental and applied biological sciences. Psychology; Gene Library; Genetic vectors; Genome, Human; Genomics; HeLa Cells; HIV; HIV 1; HIV Long Terminal Repeat; HIV-1 - metabolism; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Integrases - genetics; Integrases - metabolism; Journalism; Libraries; Microbiology; Molecular biology; Molecular Sequence Data; Mutation; Pharmacology; Plasmids; Polymerase chain reaction; Proteins; Proviruses; Proviruses - metabolism; Recombination, Genetic; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Transfection; Virology; Virus Integration; Viruses; Virus; HIV-1 virus; Retroviridae; Antiviral; Human immunodeficiency virus; Lentivirus; Provirus
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1141453

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.