PUBLICATION

Nitroreductase-Activatable Morpholino Oligonucleotides for in Vivo Gene Silencing

Authors
Yamazoe, S., McQuade, L.E., Chen, J.K.
ID
ZDB-PUB-140730-6
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping