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

The loxP (locus of crossover in P1) DNA sequence is a 34-base pair site-specific recombination sequence originally identified in the bacteriophage P1 [1]. It is composed of two 13-base pair inverted repeat elements that serve as binding sites for Cre recombinase, separated by an 8-base pair asymmetric spacer region that provides directionality to the recombination event [2]. When two loxP sites are present in a genome, the Cre enzyme facilitates a precise recombination reaction that can result in the excision, inversion, or translocation of the DNA located between them, depending on their orientation [3]. While not a traditional endogenous therapeutic target, the Cre-loxP system is an essential tool in biomedical research for generating conditional knockout and knock-in mouse models, allowing scientists to study gene function with spatial and temporal specificity [4]. In the context of advanced therapeutics, loxP sequences are utilized in gene therapy vectors to enable the precise removal of selection markers or to control the expression of therapeutic transgenes [5]. However, the clinical application of this system faces challenges, including the potential for Cre-mediated toxicity due to recombination at endogenous pseudo-loxP sites in the human genome and the risk of an immune response against the non-human Cre protein [6].

Other names

loxP siteLocus of crossover in P1Cre-lox recombination siteloxP sequence

Cre recombinase recognizes and binds to the 13-bp inverted repeats of two loxP sites, forming a synaptic complex where it catalyzes a reciprocal strand exchange and DNA cleavage/ligation, resulting in the excision, inversion, or translocation of the intervening DNA sequence depending on the relative orientation of the loxP sites [1, 2, 3].