PUBLICATION

Optochemical control over mRNA translation by photocaged phosphorodiamidate morpholino oligonucleotides in vivo

Authors
Tarbashevich, K., Ghosh, A., Das, A., Kuilya, D., Sharma, S.N., Sinha, S., Raz, E.
ID
ZDB-PUB-250417-12
Date
2025
Source
Nature communications   16: 36143614 (Journal)
Registered Authors
Raz, Erez, Tarbashevich, Katsiyarina
Keywords
none
MeSH Terms
  • Animals
  • Oligonucleotides, Antisense/genetics
  • Protein Biosynthesis*/radiation effects
  • Ultraviolet Rays
  • Embryo, Nonmammalian/metabolism
  • Morpholinos*/chemistry
  • Morpholinos*/genetics
  • Morpholinos*/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • RNA, Messenger*/genetics
  • RNA, Messenger*/metabolism
PubMed
40240365 Full text @ Nat. Commun.
Abstract
We developed an efficient, robust, and broadly applicable system for light-induced protein translation to control the production of proteins of interest and study their function. The method is based on the displacement of a single type of antisense morpholino from RNA by the uncaged guanidinium-linked morpholino (GMO)-phosphorodiamidate morpholino oligonucleotide (PMO) chimera upon UV irradiation. The GMO-PMO chimera designed here is cell-permeable and the GMO part can be produced employing a mercury-free approach compatible with the synthesis on solid support. We demonstrate the function of this optochemical approach in live embryos by inducing, at desired times and locations, the expression of proteins that label specific cells, ablate tissue regions, and affect embryonic development. Together, our results demonstrate that the cell-permeable GMO-PMO chimera offers a strategy for controlling the function of mRNAs of interest. This method allows for the production of proteins at specific times and positions within live organisms, facilitating numerous applications in biomedical research and therapy.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping