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ZFIN ID: ZDB-PUB-140321-37
Target Gene Knockdown by 2',4'-BNA/LNA Antisense Oligonucleotides in Zebrafish
Itoh, M., Nakaura, M., Imanishi, T., and Obika, S.
Date: 2014
Source: Nucleic Acid Therapeutics 24(3): 186-91 (Journal)
Registered Authors: Itoh, Motoyuki
Keywords: none
MeSH Terms:
  • Animals
  • Base Sequence
  • Codon, Initiator
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques*
  • Molecular Sequence Data
  • Morpholinos/genetics
  • Morpholinos/metabolism
  • Oligonucleotides/chemical synthesis
  • Oligonucleotides/genetics*
  • Oligonucleotides/metabolism
  • Oligonucleotides, Antisense/chemical synthesis
  • Oligonucleotides, Antisense/genetics*
  • Oligonucleotides, Antisense/metabolism
  • Protein Biosynthesis
  • Ribonuclease H/metabolism
  • Transcription Factor 7-Like 1 Protein/antagonists & inhibitors
  • Transcription Factor 7-Like 1 Protein/genetics*
  • Transcription Factor 7-Like 1 Protein/metabolism
  • Tumor Suppressor Protein p53/genetics
  • Tumor Suppressor Protein p53/metabolism
  • Zebrafish
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 24460393 Full text @ Nucleic Acid Ther.

Gene knockdowns using oligonucleotide-based approaches are useful for studying gene function in both in vitro cell culture systems and in vivo animal models. We evaluated the efficacy of 22,42-bridged nucleic acids (BNA)-modified antisense oligonucleotides (AONs) for gene knockdown in zebrafish. We used the tcf7l1a gene as a model for testing the knockdown efficacy of 22,42-BNA AONs and examined how the target sites/affinity and RNase H induction activity of 22,42-BNA AONs affect knockdown efficacy. We found that tcf7l1a gene function was knocked down by 22,42-BNA AONs that target the start codon and induce RNase H activity. Although nonspecific p53-mediated developmental defects were observed at higher doses, the effective dose of the 22,42-BNA AONs for tcf7l1a is much lower than that of morpholino oligonucleotides. Our data thus show a potential application for 22,42-BNA AONs in the downregulation of specific genes in zebrafish.