I would like to compare the features and pros/cons between antisense oligonucleotides and siRNA in oligonucleotide therapeutics. Both can be used to inhibit target gene expression with different mechanisms. What are the considerations for each in drug development?
siRNAs induce gene silencing by triggering degradation of mRNA containing their complementary sequences, a process that is mediated by RISC (RNA-Induced silencing complex) and its catalytic component argonaute which possesses endonuclease activity.
Antisense RNAs (asRNAs) are complementarity to target mRNAs .Upon their binding to target mRNAs, translation is inhibited through inhibition of the ribosome binding to the target mRNA and/or by RNase degradation of the asRNA–mRNA hybrid.
Practically, using siRNA is an efficient approach to silent gene expression compared to asRNA.
Thank you, Sima. Very helpful. ASO and siRNA use different mechanisms to degrade mRNA. Both have approved therapeutic products. With further basic investigation and more drug development research, hope more will be understood to know which mechanism is more suitable for drug development.
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