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The HIV-1 proviral DNA long terminal repeat (LTR) containing the conserved 34-bp loxBTR sequence is a specific genomic target located at both ends of the integrated HIV-1 genome. This sequence is highly conserved across various HIV-1 clinical isolates, making it an ideal candidate for gene-editing therapies aimed at a functional cure (Karpinski et al., 2016, Nature Methods). The loxBTR site is specifically recognized by the engineered recombinase Brec1, which facilitates the precise excision of the entire provirus from the host cell's DNA (Karpinski et al., 2016). By removing the integrated viral DNA, this approach aims to eliminate the latent viral reservoir that persists despite antiretroviral therapy (Buchholz et al., 2021, Gene Therapy). This target represents a shift from traditional viral enzyme inhibition to direct genomic eradication of the pathogen. Successful targeting of the loxBTR sequence results in the restoration of the host cell's genomic integrity and the prevention of further viral replication (Karpinski et al., 2016).
Site-specific recombination leading to the excision of the proviral DNA from the host genome.
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