Prion protein gene regulatory region (PRNP regulatory region) (PRNP regulatory region)

The Prion protein gene regulatory region (PRNP regulatory region) is the genomic segment, including the promoter, exon 1, and intron 1, that controls the transcription of the PRNP gene [1.1.1, 1.4.1]. This gene encodes the cellular prion protein (PrPC), a membrane-anchored glycoprotein whose misfolding into the pathogenic PrPSc isoform is the central event in fatal neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) and fatal familial insomnia [1.1.2, 1.3.2]. Because PrPC is essential for the replication and neurotoxicity of prions, the regulatory region is a primary target for "substrate reduction" therapies aimed at lowering PrPC levels at the source [1.2.2, 1.4.4]. Experimental approaches include the use of CRISPR interference (CRISPRi) for transcriptional silencing and CRISPR/Cas9 for permanent gene knockout [1.2.3, 1.2.5]. Additionally, the presence of G-quadruplex DNA structures within this region provides a potential site for small-molecule ligands to modulate gene expression [1.4.4]. While no therapies targeting this genomic region are currently approved, it remains a critical focus for developing durable genetic treatments for both sporadic and inherited prion disorders [1.2.2, 1.2.5].

Other names

PRNP promoterPRNP 5' regulatory regionPrion protein gene control regionCD230 gene regulatory region

Transcriptional silencing, genomic deletion, and G-quadruplex stabilization to reduce PrPC expression.