Table 1.

Differences between small-interfering RNA and antisense oligonucleotides

	siRNA	ASO
Structure	Double-stranded RNA + two 3’ end overhanging nucleotides	Single-stranded DNA + flanking by modified RNA-like segments (gapmer)
Ideal length	21 nucleotides	15–25 nucleotides
Cellular entry	Requires conjugation to carrier for hepatocyte uptake	Can be taken into hepatocytes in unconjugated form
Accumulation	In endosomes	In cytoplasm
Dosing frequency	Less frequent (monthly)	More frequent (weekly or biweekly)
Target mRNA binding	Requires RISC formation	Can bind to target alone
Primary gene silencing mechanism	Target RNA cleavage by Argonaute	Target RNA cleavage by RNAse-H

siRNA, small-interfering RNA; ASO, antisense oligonucleotide; mRNA, messenger RNA; RISC, RNA-induced silencing complex.