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Enum: OligonucleotideMechanismEnum

Molecular mechanism of action of a therapeutic oligonucleotide. Covers the three core single-stranded antisense (ASO) paradigms described in Sang et al. 2024 (PMID:38914784) - RNase H-mediated degradation, splice modulation, and steric blockade - together with the double-stranded RNA interference (RNAi) paradigm used by siRNA therapeutics, in which the guide strand is loaded into RISC and Argonaute-2 cleaves the sequence-matched transcript.

URI: dismech:enum/OligonucleotideMechanismEnum

Permissible Values

Value Meaning Description Additional Info
RNASE_H_KNOCKDOWN GO:0004523 ASO:RNA heteroduplex recruits RNase H1 to cleave the target mRNA, reducing a ... Title: RNase H knockdown
RNAI_KNOCKDOWN GO:0070551 Double-stranded siRNA guide strand is loaded into RISC and Argonaute-2 cataly... Title: RNAi knockdown
SPLICE_MODULATION_EXON_SKIPPING None ASO occludes a splice site or splicing element to exclude an exon, restoring ... Title: Splice modulation (exon skipping)
SPLICE_MODULATION_EXON_INCLUSION None ASO blocks an intronic splicing silencer to promote exon inclusion (e Title: Splice modulation (exon inclusion)
STERIC_BLOCKADE None ASO sterically blocks ribosome access or other RNA-protein interactions witho... Title: Steric translational blockade
MIRNA_MODULATION None ASO sequesters or inhibits a microRNA (antimiR) or blocks a miRNA binding sit... Title: miRNA modulation

Slots

Name Description
oligonucleotide_mechanism Molecular mechanism of action of a therapeutic oligonucleotide
aso_mechanism Deprecated alias of oligonucleotide_mechanism

Aliases

  • AsoMechanismEnum

Identifier and Mapping Information

Schema Source

  • from schema: https://w3id.org/monarch-initiative/dismech

LinkML Source

name: OligonucleotideMechanismEnum
description: Molecular mechanism of action of a therapeutic oligonucleotide. Covers
  the three core single-stranded antisense (ASO) paradigms described in Sang et al.
  2024 (PMID:38914784) - RNase H-mediated degradation, splice modulation, and steric
  blockade - together with the double-stranded RNA interference (RNAi) paradigm used
  by siRNA therapeutics, in which the guide strand is loaded into RISC and Argonaute-2
  cleaves the sequence-matched transcript.
from_schema: https://w3id.org/monarch-initiative/dismech
aliases:
- AsoMechanismEnum
rank: 1000
permissible_values:
  RNASE_H_KNOCKDOWN:
    text: RNASE_H_KNOCKDOWN
    description: ASO:RNA heteroduplex recruits RNase H1 to cleave the target mRNA,
      reducing a toxic or gain-of-function protein
    meaning: GO:0004523
    title: RNase H knockdown
    aliases:
    - RNA-DNA hybrid ribonuclease activity
  RNAI_KNOCKDOWN:
    text: RNAI_KNOCKDOWN
    description: Double-stranded siRNA guide strand is loaded into RISC and Argonaute-2
      catalytically cleaves the sequence-matched mRNA, reducing a toxic or gain-of-function
      protein (e.g., patisiran, vutrisiran, inclisiran)
    meaning: GO:0070551
    title: RNAi knockdown
    aliases:
    - endoribonuclease activity, cleaving siRNA-paired mRNA
  SPLICE_MODULATION_EXON_SKIPPING:
    text: SPLICE_MODULATION_EXON_SKIPPING
    description: ASO occludes a splice site or splicing element to exclude an exon,
      restoring an in-frame transcript (e.g., DMD exon skipping)
    title: Splice modulation (exon skipping)
  SPLICE_MODULATION_EXON_INCLUSION:
    text: SPLICE_MODULATION_EXON_INCLUSION
    description: ASO blocks an intronic splicing silencer to promote exon inclusion
      (e.g., nusinersen at SMN2 ISS-N1)
    title: Splice modulation (exon inclusion)
  STERIC_BLOCKADE:
    text: STERIC_BLOCKADE
    description: ASO sterically blocks ribosome access or other RNA-protein interactions
      without inducing cleavage (e.g., fomivirsen)
    title: Steric translational blockade
  MIRNA_MODULATION:
    text: MIRNA_MODULATION
    description: ASO sequesters or inhibits a microRNA (antimiR) or blocks a miRNA
      binding site
    title: miRNA modulation