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Peer-reviewedCC BYRSC chemical biology

Deactivating siRNA activity with bioorthogonal inverse-electron-demand Diels–Alder chemistry

  • Kaifeng Zhao1
  • Kaleena Basran1
  • Loïc Courville-Fortin1
  • Nathan W. Luedtke1,2
  1. 1Department of Chemistry, McGill University Montréal H3A 0B8 Canada
  2. 2Department of Pharmacology and Therapeutics, McGill University Montréal H3G 1Y6 Canada
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Abstract

Small interfering RNAs (siRNAs) were prepared with vinyl nucleobases and imperfect duplex reaction sites that enable selective inverse electron-demand Diels–Alder (IEDDA) reactions with tetrazines in living cells. These bioorthogonal reactions attenuate gene silencing of both reporter and endogenous genes, establishing a small-molecule strategy for deactivating siRNA activity.

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Cite

BibTeXRIS
BibTeX
@article{zhao2026deactivating,
  title = {{Deactivating siRNA activity with bioorthogonal inverse-electron-demand Diels–Alder chemistry}},
  author = {Kaifeng Zhao and Kaleena Basran and Loïc Courville-Fortin and Nathan W. Luedtke},
  journal = {RSC chemical biology},
  year = {2026},
  month = oct,
  doi = {10.1039/d6cb00284f},
  url = {https://europepmc.org/article/PMC/PMC13725365},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Deactivating siRNA activity with bioorthogonal inverse-electron-demand Diels–Alder chemistry
AU  - Kaifeng Zhao
AU  - Kaleena Basran
AU  - Loïc Courville-Fortin
AU  - Nathan W. Luedtke
PY  - 2026
DA  - 2026/10/12
JO  - RSC chemical biology
DO  - 10.1039/d6cb00284f
UR  - https://europepmc.org/article/PMC/PMC13725365
AB  - Small interfering RNAs (siRNAs) were prepared with vinyl nucleobases and imperfect duplex reaction sites that enable selective inverse electron-demand Diels–Alder (IEDDA) reactions with tetrazines in living cells. These bioorthogonal reactions attenuate gene silencing of both reporter and endogenous genes, establishing a small-molecule strategy for deactivating siRNA activity.
SN  - 2633-0679
ER  -