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Global Translational Medicine Small RNA therapy for pancreatic cancer

A

B

C

D

Figure 2. Schematic diagram of the mechanisms of action of different types of small RNA drugs, including miRNA, siRNA, ASO, and aptamer. (A) miRNAs exert their effects
by binding to the 3′ UTR, 5′ UTR, or ORF of target mRNAs, which leads to either mRNA degradation or inhibition of mRNA translation. (B) siRNAs exert their effects by
binding to the ORF of target mRNAs, which leads to mRNA degradation. (C) In the first scenario, ASO specifically target RNA molecules, leading to the formation of ASO-
RNA heteroduplexes. These heteroduplexes serve as substrates for RNase enzymes located in the cytoplasm. Once the ASO-RNA heteroduplexes are formed, RNases initiate
the degradation process of the RNA within these structures. In the second scenario, ASOs bind to the target mRNA sequence, leading to translational arrest by inhibiting its
interaction with the 40S ribosomal subunit or preventing its assembly on the 40S or 60S ribosomal subunit. In the third scenario, a gene with three exons (exon 1, 2, and 3) and
two introns is shown. An ASO binds to the junction of the intron and exon2, blocking the action of spliceosome and causing exon 2 to be spliced out along with the introns.
As a result, the mature mRNA lacks exon 2. (D) Aptamers recognizes target molecules through their three-dimensional conformations and have high binding affinities.
Abbreviations: siRNA: Small interfering RNA; ASO: Antisense oligonucleotide; UTR: Untranslated region; ORF: Open reading frame; RNase: Ribonuclease; miRNA:
MicroRNA.

Volume 4 Issue 2 (2025) 19 doi: 10.36922/gtm.8247