Off-target genomic DNA loci with partial complementarity to Pleckstrin and Sec7 domain containing 3 guide RNA (PSD3 off-target loci)

Off-target genomic DNA loci with partial complementarity to Pleckstrin and Sec7 domain containing 3 (PSD3) guide RNA are unintended genomic sites where CRISPR-Cas9 or other RNA-guided endonucleases may bind and induce DNA modifications. The PSD3 gene is a therapeutic target under investigation for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) due to its role in hepatic lipid accumulation (PMID: 34135068). During the gene-editing process, the guide RNA (gRNA) designed for PSD3 may hybridize with other DNA sequences that possess high homology, leading to "off-target" cleavage (PMID: 23792610). These loci do not serve a therapeutic purpose; instead, they represent a significant safety concern, as unintended mutations can lead to genotoxicity or chromosomal translocations (PMID: 24253444). If these off-target effects occur within tumor suppressor genes or oncogenic regions, they could potentially trigger malignant transformation. Consequently, the identification and minimization of these sites are critical for the clinical development of PSD3-targeted genetic therapies. Monitoring is typically performed using high-throughput sequencing methods like GUIDE-seq or CIRCLE-seq to ensure genomic integrity (PMID: 25513782).

Other names

PSD3 gRNA off-target sitesNon-specific CRISPR-Cas9 cleavage sitesUnintended genomic modificationsCRISPR off-targets

Unintended RNA-guided DNA cleavage or modification at genomic sites with sequence homology to the primary PSD3 target sequence.