Off-target genomic DNA loci with partial complementarity to the Erythropoietin receptor guide RNA (EPOR off-target loci)

Off-target genomic DNA loci with partial complementarity to the Erythropoietin receptor (EPOR) guide RNA represent unintended sites in the genome where CRISPR-based gene editing tools may bind and introduce mutations (Fu et al., 2013). These sites typically possess sequence similarity to the primary target sequence within the EPOR gene, leading the Cas9 nuclease or other editors to recognize them erroneously (Zhang et al., 2015). While the primary goal of EPOR-targeted therapy is to modulate erythropoiesis or treat conditions like erythrocytosis, these off-target interactions pose significant safety risks, including the potential for insertional mutagenesis or chromosomal translocations (NIH, 2023). Monitoring these loci is a critical component of preclinical safety assessments for gene therapies (FDA, 2022). Advanced sequencing techniques like GUIDE-seq or CIRCLE-seq are often employed to identify and quantify the frequency of these unintended edits (Tsai et al., 2015). Minimizing such interactions is essential for ensuring the specificity and safety of therapeutic interventions targeting the EPOR pathway (Nature Communications, 2021). The presence of these loci can lead to unintended gene silencing or activation if they occur within regulatory regions or coding sequences of other genes (PubChem, 2024). Consequently, bioinformatic prediction tools are used alongside empirical validation to select guide RNAs with the highest specificity for the EPOR gene (PubMed, 2022).

Other names

CRISPR off-target sitesUnintended genomic cleavage sitesEPOR gRNA off-targetsNon-specific DNA binding sites

Unintended binding and cleavage of DNA sequences that share partial homology with the designed guide RNA (gRNA) for the Erythropoietin receptor (EPOR) gene.