This article discusses three RNA therapeutic technologies: RNA interference (RNAi), antisense oligonucleotides (ASOs), and steric-blocking oligonucleotides. RNAi and ASOs downregulate gene expression by degrading targeted mRNA, while steric-blocking oligonucleotides block access of cellular machinery to pre-mRNA and mRNA without degradation. Steric-blocking oligonucleotides can redirect alternative splicing, repair defective RNA, restore protein production, or downregulate gene expression. They can be chemically modified to enhance their drug-like properties. The review highlights the challenges and advancements in delivering these oligonucleotides intracellularly, particularly for treating genetic disorders like Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). Clinical trials for DMD using chemically modified siRNA show promising results, indicating that RNA-blocking oligonucleotides have significant potential in treating genetic disorders.This article discusses three RNA therapeutic technologies: RNA interference (RNAi), antisense oligonucleotides (ASOs), and steric-blocking oligonucleotides. RNAi and ASOs downregulate gene expression by degrading targeted mRNA, while steric-blocking oligonucleotides block access of cellular machinery to pre-mRNA and mRNA without degradation. Steric-blocking oligonucleotides can redirect alternative splicing, repair defective RNA, restore protein production, or downregulate gene expression. They can be chemically modified to enhance their drug-like properties. The review highlights the challenges and advancements in delivering these oligonucleotides intracellularly, particularly for treating genetic disorders like Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). Clinical trials for DMD using chemically modified siRNA show promising results, indicating that RNA-blocking oligonucleotides have significant potential in treating genetic disorders.