Genomic DNA target locus (CRISPR-Cas) (DNA target)

A sequence-defined double-stranded DNA locus serves as the precise molecular target for CRISPR-Cas-based genome editing technologies. This target is defined by the presence of a Protospacer Adjacent Motif (PAM) and an adjacent protospacer sequence that is complementary to a synthetic guide RNA (gRNA) [1][2]. The PAM sequence is essential for the initial binding of the Cas nuclease, while the protospacer complementarity ensures the specificity of the interaction [3]. Once the CRISPR-Cas ribonucleoprotein complex binds to this specific locus, it induces a double-strand break or chemical modification of the DNA, which is then processed by cellular repair mechanisms to achieve gene disruption, correction, or insertion [4]. In clinical applications, these loci are chosen based on their role in disease pathogenesis, such as the BCL11A enhancer in hemoglobinopathies or the TTR gene in amyloidosis [5][6]. The therapeutic efficacy of drugs targeting these loci depends on the precision of the gRNA-DNA match and the efficiency of the subsequent DNA repair process [7].

Other names

Sequence-defined double-stranded DNA locus containing a compatible PAM and guide-complementary protospacerCRISPR target siteProtospacerPAM-adjacent genomic sequenceGenomic target siteCRISPR-Cas9 target DNA

RNA-guided site-specific DNA cleavage followed by cellular DNA repair (NHEJ or HDR), or direct chemical modification via base/prime editing.