, 2007). Cre recombinase Selleckchem CDK inhibitor is widely used in mouse genetics and has been intensively studied ( Glaser et al., 2005 and Van Duyne, 2001). Particularly in clinical applications, it seems to be advantageous that such recombinases, including Tre, neither produce DSBs nor require additional host factors such as the NHEJ pathway. As a result, the recombination process is very precise and usually error-free ( Glaser et al., 2005 and Van Duyne, 2001). Nevertheless, prior to clinical application various potential

problems connected with the Tre technology have to be resolved. For example, current Tre-recombinase was raised against a primary HIV-1 subtype A isolate (Blackard et al., 1999). It is therefore expected that for broader applications a Tre-recombinase also recognizing a majority of HIV-1 subtypes must be developed. Likewise, Tre treatment may select for outgrowth of resistant viruses resulting from target (loxLTR) site mutation. Both aspects may be addressed by identifying Tre target sequences that are highly conserved in the LTRs of a vast majority of HIV-1 isolates. The recent development of a novel “locus of recombination Selleck GSK2118436 site” search tool and the description of a collection of conserved sequences covering a maximum of HIV-1 variants will

certainly be helpful in achieving this goal (McIntyre et al., 2009 and Surendranath et al., 2010). Even if it turns out that a sterilizing cure cannot be achieved, Tre technology may also be applicable in a functional cure for ex vivo treatment of PBMCs. For this, Tre-recombinase could be expressed as a fusion with a cell-penetrating protein transduction domain (PTD) or membrane translocation motif (TLM) ( Fonseca et al., 2009). As reported recently, directly adding recombinant PTD/TLM-Tre fusion protein to a productively

infected T cell culture resulted in efficient protein translocation and excision of the full-length HIV-1 proviral Niclosamide DNAs from their chromosomal integration sites ( Mariyanna et al., 2012). The growing recognition that a cure for HIV infection is not only needed but also feasible is based on significant advances in basic, translational, and clinical research (Deeks et al., 2012). The remarkable case of the “Berlin patient” particularly revived the idea of gene therapy strategies to eradicate HIV (Kiem et al., 2012 and van Lunzen et al., 2011). Indeed, expression of in vitro engineered enzymes disrupting the CCR5 surface receptor and/or excising the HIV-1 proviral DNA may become critical components of future therapies aiming at virus eradication. It is generally expected that, if achievable at all, no single approach will lead to a sterilizing cure. Rather, a clever combination of drug treatments, therapeutic vaccination strategies, possibly in combination with antiviral gene therapy, likely offers the highest hope for defeating HIV.