Off-target genomic DNA loci with partial homology to APOE single guide RNA (APOE sgRNA off-targets)

Off-target genomic DNA loci with partial homology to APOE single guide RNA (sgRNA) refer to unintended sites in the human genome where CRISPR-based gene editing tools may bind and introduce modifications. These sites possess sequence similarity to the intended target sequence within the Apolipoprotein E (APOE) gene, leading the Cas9 nuclease or other editors to recognize them as targets (NIH, 2014). While the primary goal of APOE-targeted therapy is often to modify alleles associated with Alzheimer's disease, such as APOE4, off-target effects pose significant safety risks (Nature Communications, 2024). Unintended edits at these loci can result in gene disruptions, chromosomal rearrangements, or the activation of oncogenes, potentially leading to cellular toxicity or cancer (Cell Stem Cell, 2014). Monitoring and minimizing these off-target interactions is a critical component of developing safe CRISPR-based therapeutics (MIT, 2019). Advanced sequencing techniques like GUIDE-seq and CIRCLE-seq are employed to identify and quantify these risks during preclinical development to ensure therapeutic precision and patient safety.

Other names

APOE CRISPR off-target sitesNon-specific APOE sgRNA binding sitesUnintended genomic cleavage sitesHomologous APOE off-targets

Unintended DNA cleavage or modification via sequence-specific binding of a CRISPR-Cas complex to non-target loci with sequence homology.