Friday, June 29, 2007

Splicing out integrated HIV

Those of us doing mouse work are probably already familiar with the CRE-lox system, which uses a recombinase called CRE to excise fragments of DNA in the genome that are flanked by loxP sites (floxed in the lingo). This technique is mostly used for conditional transgenic to gain tissue-specific Ko for example, which is the bane of my existence.

Well some clever folks in Germany decided to evolve the CRE enzyme in vitro to recognise the viral LTR flanking sites of HIV instead of loxP. The results are quite encouraging:

"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."