Chromosome 9 open reading frame 72 GGGGCC sense repeat RNA (G4C2 RNA)

The Chromosome 9 open reading frame 72 (C9orf72) GGGGCC sense repeat RNA is a pathological transcript resulting from a hexanucleotide repeat expansion in the first intron of the C9orf72 gene [2, 9]. This expansion is recognized as the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) [10, 14]. The sense RNA transcript exerts neurotoxicity through a gain-of-function mechanism, primarily by forming nuclear RNA foci that sequester essential RNA-binding proteins and by serving as a template for repeat-associated non-AUG (RAN) translation into toxic dipeptide repeat proteins (DPRs) [7, 16]. Therapeutic strategies aim to selectively degrade or block these toxic transcripts using antisense oligonucleotides (ASOs), siRNAs, or RNA-targeting CRISPR-Cas systems [1, 5, 30]. While clinical trials for ASO candidates such as BIIB078 and WVE-004 have been conducted, they have encountered significant hurdles related to efficacy and safety [11, 24]. Efficacy is typically monitored through the measurement of DPR levels and neurofilament light chain in the cerebrospinal fluid [2, 22].

Other names

C9orf72 G4C2 sense repeat RNAC9orf72 hexanucleotide repeat expansion sense RNAr(G4C2)expSense C9orf72-repeat transcriptC9orf72 HRE RNAGGGGCC repeat RNA

RNase H-mediated RNA degradation, steric blocking of translation, and RNA cleavage