What is the Difference Between RNA Interference and Antisense Oligonucleotide?

RNA interference (RNAi) and antisense oligonucleotides (ASOs) are both RNA-based therapeutic approaches that target gene expression, but they differ in their mechanisms of action and the specific effects they produce.

RNA Interference (RNAi):

• Triggered by double-stranded RNA (dsRNA).
• Causes sequence-specific mRNA degradation of single-stranded target RNAs in response to dsRNA.
• Mediated by small interfering RNA duplexes (siRNAs), which are produced from long dsRNA by enzymatic cleavage in the cell.
• siRNAs are approximately 21-nucleotide length and have a base-paired structure.

Antisense Oligonucleotides (ASOs):

• Single-stranded DNA oligonucleotides that are complementary to the mRNA target.
• Downregulate a molecular target, usually achieved by induction of RNase H endonuclease activity that cleaves the RNA-DNA heteroduplex.
• Other ASO-driven mechanisms include inhibition of 5′ cap formation, alteration of splicing process (splice-switching), and steric hindrance of ribosomal activity.

In summary, RNAi is triggered by dsRNA and causes sequence-specific mRNA degradation, while ASOs are single-stranded DNA oligonucleotides that bind to complementary mRNA targets, leading to various effects such as RNase H-mediated cleavage, inhibition of 5′ cap formation, and alteration of splicing processes. Both approaches have therapeutic potential in various diseases, including cancer and neurodegeneration.

Comparative Table: RNA Interference vs Antisense Oligonucleotide

Here is a table comparing the differences between RNA interference (RNAi) and antisense oligonucleotides (ASO):

RNAi and ASO are both RNA therapeutic technologies that exploit oligonucleotides to target RNA, but they have distinct mechanisms of action and structures.