ZFIN ID: ZDB-PUB-140730-6
Nitroreductase-Activatable Morpholino Oligonucleotides for in Vivo Gene Silencing
Yamazoe, S., McQuade, L.E., Chen, J.K.
Date: 2014
Source: ACS Chemical Biology   9(9): 1985-90 (Journal)
Registered Authors: Chen, James K.
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Chemistry Techniques, Synthetic
  • Embryo, Nonmammalian/drug effects*
  • Escherichia coli Proteins/metabolism*
  • Female
  • Gene Silencing*
  • HEK293 Cells
  • Humans
  • Light
  • Morpholinos/chemistry
  • Morpholinos/metabolism
  • Morpholinos/pharmacology*
  • Nitroreductases/metabolism*
  • Zebrafish/embryology
  • Zebrafish/genetics
PubMed: 25069083 Full text @ ACS Chem. Biol.
ABSTRACT
Phosphorodiamidate morpholino oligonucleotides are widely used to interrogate gene function in whole organisms, and light-activatable derivatives can reveal spatial and temporal differences in gene activity. We describe here a new class of caged morpholino oligonucleotides that can be activated by the bacterial nitroreductase NfsB. We characterize the activation kinetics of these reagents in vitro and demonstrate their efficacy in zebrafish embryos that express NfsB either ubiquitously or in defined cell populations. In combination with transgenic organisms, such enzyme-actuated antisense tools will enable gene silencing in specific cell types, including tissues that are not amenable to optical targeting.
ADDITIONAL INFORMATION