These results demonstrate that RNA ASOs targeting the 5′ flanking G4C2 sequence are sufficient to block RAN translation independently of C9ORF72 RNAs degradation and identify the 5′–3′ scanning of ribosomes as a potential therapeutic target in C9ORF72 ALS/FTD. The gene discussed is C9orf72; the disease is amyotrophic lateral sclerosis.