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The 34-bp loxBTR sequence is a specific DNA target located within the long terminal repeats (LTRs) of the HIV-1 provirus, which is the form of the virus integrated into the host cell's genome (Karpinski et al., 2016, Nature Biotechnology). This sequence was identified as a highly conserved site across a broad range of HIV-1 clinical isolates, making it an ideal candidate for gene therapy interventions. The primary therapeutic agent designed to interact with this sequence is Brec1, an evolved site-specific recombinase derived from the Cre recombinase. Brec1 recognizes the loxBTR sites flanking the integrated provirus and catalyzes a recombination event that physically excises the viral DNA from the host chromosome (Hauber et al., 2013, PLOS Pathogens). This approach aims to achieve a sterilizing cure for HIV-1 by permanently removing the latent viral reservoir that persists despite antiretroviral therapy. Unlike traditional treatments that only suppress viral replication, targeting the loxBTR sequence allows for the direct elimination of the genetic blueprint of the virus from infected cells.
Site-specific recombination leading to the excision of integrated HIV-1 proviral DNA from the host genome.
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