Target intelligence / Profile preview

Locus of crossover in P1 (loxP) DNA site (loxP)

Target
loxP
Molecular classification
DNA sequence, Recombination site
01

Overview

The locus of crossover in P1 (loxP) is a 34-base pair DNA sequence derived from the P1 bacteriophage that serves as the specific recognition site for the Cre recombinase enzyme (Sauer, B., 1998, Methods in Enzymology). It consists of two 13-bp palindromic inverted repeats flanking an 8-bp asymmetric spacer region that determines the directionality of the site (Nagy, A., 2000, Genesis). When two loxP sites are introduced into a genome, the Cre-loxP system allows for precise genomic manipulation; depending on the orientation and location of the sites, Cre can catalyze the excision, inversion, or translocation of the intervening DNA (Hardy, S. et al., 1997, Journal of Virology). While not a traditional therapeutic target for small molecules, loxP sites are essential components of conditional gene knockout technologies used to model human diseases and are increasingly utilized in experimental gene therapies. These therapies leverage the system to achieve spatial or temporal control over transgene expression, such as the targeted removal of viral DNA or the activation of therapeutic genes in specific tissues (Kim, H. et al., 2018, Nature Communications; Buchholz, F. et al., 2015, Trends in Biotechnology).

Other names
loxP siteLocus of X-over P1loxP sequenceFloxed site
02

Mechanism of action

Cre recombinase binds to the 13-bp inverted repeats of two loxP sites, forming a synaptic complex where it facilitates a reciprocal strand exchange through a covalent protein-DNA intermediate, leading to site-specific recombination (Van Duyne, G. D., 2015, Microbiology Spectrum).

03

Biological functions

Site-specific recombinationDNA excisionDNA inversionDNA translocationGene regulation
04

Disease associations

CancerGenetic disorderInfection
05

Safety considerations

Off-target recombination at pseudo-loxP sites in the mammalian genome (Loonstra, A. et al., 2001, Genesis)Chromosomal instability and unintended translocationsCytotoxicity associated with high or prolonged Cre recombinase expressionImmunogenicity of the bacterial-derived Cre enzyme in human clinical applications (Schmidt-Supprian, M. & Rajewsky, K., 2007, Nature Immunology)
06

Interacting drugs

Cre recombinase
07

Biomarkers

loxP sequence detectionCre-mediated recombination efficiencyReporter gene expression (e.g., GFP/LacZ) following excision

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