Target intelligence / Profile preview

HIV-1 proviral DNA long terminal repeat loxBTR sequence (loxBTR)

Target
loxBTR
Molecular classification
Nucleic acid, Viral DNA sequence, Long terminal repeat (LTR)
01

Overview

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).

Other names
loxBTRHIV-1 LTR target siteBrec1 target sequenceHIV-1 proviral LTR
02

Mechanism of action

Site-specific recombination leading to the excision of the proviral DNA from the host genome.

03

Biological functions

Viral transcriptionViral integrationViral replicationGenomic stability
04

Disease associations

HIV-1 infectionAcquired Immunodeficiency Syndrome (AIDS)
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Safety considerations

Off-target genomic cleavageImmunogenicity of the recombinase enzymeIncomplete excision of the provirusPotential for insertional mutagenesis during delivery
06

Interacting drugs

Brec1 (recombinase)
07

Biomarkers

HIV-1 proviral DNA loadCell-associated HIV-1 RNACD4+ T-cell countPlasma viral load

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