PUBLICATION
Small Molecule Control of Morpholino Antisense Oligonucleotide Function through Staudinger Reduction
- Authors
- Darrah, K., Wesalo, J., Lukasak, B., Tsang, M., Chen, J.K., Deiters, A.
- ID
- ZDB-PUB-211028-5
- Date
- 2021
- Source
- Journal of the American Chemical Society 143(44): 18665-18671 (Journal)
- Registered Authors
- Chen, James K., Tsang, Michael
- Keywords
- none
- MeSH Terms
-
- Animals
- Embryo, Nonmammalian/drug effects*
- Fluorescent Dyes
- Gene Knockdown Techniques
- Genes, Developmental
- Nucleic Acid Conformation
- Oligonucleotides/chemistry
- Oligonucleotides, Antisense/chemistry*
- Oligonucleotides, Antisense/pharmacology*
- Rhodamines
- Thionucleotides
- Zebrafish/embryology
- PubMed
- 34705461 Full text @ J. Am. Chem. Soc.
Citation
Darrah, K., Wesalo, J., Lukasak, B., Tsang, M., Chen, J.K., Deiters, A. (2021) Small Molecule Control of Morpholino Antisense Oligonucleotide Function through Staudinger Reduction. Journal of the American Chemical Society. 143(44):18665-18671.
Abstract
Conditionally activated, caged morpholino antisense agents (cMOs) are tools that enable the temporal and spatial investigation of gene expression, regulation, and function during embryonic development. Cyclic MOs are conformationally gated oligonucleotide analogs that do not block gene expression until they are linearized through the application of an external trigger, such as light or enzyme activity. Here, we describe the first examples of small molecule-responsive cMOs, which undergo rapid and efficient decaging via a Staudinger reduction. This is enabled by a highly flexible linker design that offers opportunities for the installation of chemically activated, self-immolative motifs. We synthesized cyclic cMOs against two distinct, developmentally relevant genes and demonstrated phosphine-triggered knockdown of gene expression in zebrafish embryos. This represents the first report of a small molecule-triggered antisense agent for gene knockdown, adding another bioorthogonal entry to the growing arsenal of gene knockdown tools.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping