Rhodopsin (RHO) genomic target site (RHO locus)

The Rhodopsin (RHO) genomic target site refers to a specific DNA sequence within the RHO gene (UniProt P08100) targeted by engineered CRISPR-Cas9 systems for therapeutic intervention. The RHO gene encodes the rhodopsin protein, a G protein-coupled receptor (GPCR) essential for visual phototransduction in rod photoreceptor cells (PubMed: 29024615). Mutations in this locus, particularly the P23H mutation, are a primary cause of autosomal dominant retinitis pigmentosa (adRP), a condition characterized by progressive vision loss (PubMed: 32034150). Therapeutic approaches like EDIT-103 utilize Streptococcus pyogenes Cas9 (SpCas9) and a single guide RNA (sgRNA) to induce double-strand breaks at this site. This mechanism aims to selectively disrupt the mutant allele or facilitate gene replacement to restore normal function (Editas Medicine, 2023). This genomic targeting strategy is designed to prevent the accumulation of misfolded rhodopsin proteins that lead to photoreceptor cell death. Safety considerations for targeting this locus include minimizing off-target effects and managing the immunogenicity of the Cas9 enzyme (PubMed: 30635552).

Other names

RHO geneOPN2RP4Rhodopsin locusOpsin 2

Gene editing via CRISPR-Cas9 mediated double-strand breaks followed by non-homologous end joining (NHEJ) to disrupt mutant alleles or facilitate gene replacement.