Centrosomal protein of 290 kDa (CEP290)

Centrosomal protein of 290 kDa (CEP290) is a large structural protein essential for the formation and maintenance of primary cilia, which act as cellular antennae for sensory perception and signaling [11, 17, 18]. It localizes to the transition zone of cilia and the centrosome, where it regulates protein trafficking and microtubule organization [11, 15, 17]. Mutations in the CEP290 gene lead to a spectrum of ciliopathies, most notably Leber congenital amaurosis type 10 (LCA10), a severe form of inherited childhood blindness [1, 3, 11, 21]. Other associated conditions include Joubert syndrome, Meckel-Gruber syndrome, and Senior-Løken syndrome [11, 17, 22]. Due to its critical role in retinal function and the prevalence of specific deep intronic mutations (e.g., c.2991+1655A>G), CEP290 has become a prominent therapeutic target for advanced genetic medicines [3, 7, 21]. Current therapeutic strategies include antisense oligonucleotides like sepofarsen, which corrects aberrant splicing, and CRISPR-based gene editing tools like EDIT-101, which directly removes pathogenic mutations [1, 3, 5, 13]. These treatments aim to restore functional CEP290 protein levels in photoreceptor cells to preserve or improve vision in patients with LCA10 [7, 10, 21].

Other names

CEP290NPHP6BBS14JBTS5SLSN6LCA10MKS4POC33H11AgCT87rd16Nephrocystin-6

RNA splicing modulation via antisense oligonucleotides to block cryptic splice sites and restore normal mRNA transcripts [3, 4, 9, 10]; In vivo gene editing using CRISPR/Cas9 to remove or invert pathogenic mutations in the CEP290 gene [1, 2, 5, 7].