Prion protein messenger RNA (PRNP mRNA)

Prion protein messenger RNA (PRNP mRNA) is the transcript responsible for the synthesis of the cellular prion protein (PrPC), a glycosylphosphatidylinositol-anchored glycoprotein primarily expressed in the central nervous system (UniProt P04156). While the exact physiological role of PrPC is still being elucidated, it is known to be involved in copper homeostasis, neuroprotection, and the maintenance of peripheral myelin (PubMed: 27499021). In prion diseases, such as Creutzfeldt-Jakob disease (CJD), the normal PrPC undergoes a post-translational conformational change into a pathogenic, misfolded isoform known as PrPSc, which aggregates and causes rapid neurodegeneration (NIH: Prion Diseases). Because PrPC is the essential substrate for the formation of toxic PrPSc, reducing its expression by targeting PRNP mRNA is a primary therapeutic strategy. Antisense oligonucleotides (ASOs), such as ION717, are designed to bind to PRNP mRNA and trigger its degradation via RNase H, thereby lowering the levels of PrPC and slowing disease progression (Ionis Pharmaceuticals; JCI Insight: 135937). This approach is currently being investigated in clinical trials as a potential disease-modifying therapy for both sporadic and genetic forms of prion disease.

Other names

PRNP mRNAPrP mRNAMajor prion protein mRNACD230 mRNAASCR mRNAPrP27-30 mRNAPrP33-35C mRNA

Antisense oligonucleotide-mediated degradation of mRNA via RNase H recruitment to reduce the expression of the cellular prion protein (PrPC).