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What is the Main Difference Between siRNA and ASO?

1. The chemical structure

  ASO is single-stranded, and siRNA is double-stranded

2. Mechanism of action

  ASO either degrades target mRNA through RNase H, interferes mRNA function with steric effects or affects mRNA shearing, or acts on miRNA

  siRNA degrades mRNA mainly through RISC

3. The cellular space where the drug is exerted

  Rnase H is present in both cytoplasm and nucleus, ASO can play a role in cytoplasm and nucleus, but RISC is only present in the cytoplasm, so siRNA is only present in the cytoplasm.

4. Duration of action and whether it can be amplified

  RISC can repeatedly act on the target mRNA; the effect will be longer

  The released sense strand of siRNA may be degraded and can also be used as a primer to amplify dsRNA by target mRNA as a template under the catalysis of RNA-dependent RNA polymerase. dsRNA is degraded into siRNA by Dicer and enters the RNAi cycle. Thus, the drug effect is amplified cascaded

5. Safety/Toxicity

  The toxicity of ASO is usually greater than that of siRNA, the liver and kidney toxicity of ASO is greater than that of siRNA, and the risk of thrombocytopenia of ASO (related to its structure and mechanism of action)