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Conditionally Activated ("Caged") Oligonucleotides

Linlin Yang1, Ivan J Dmochowski1

  • 1Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA.

Molecules (Basel, Switzerland)
|April 3, 2021
PubMed

Insights

Conditionally activated oligonucleotides offer precise control for biological studies. New caging strategies, including circular and protease-activated probes, enhance gene regulation and transcriptome analysis in living tissues.

Area of Science:

  • Molecular Biology
  • Biotechnology
  • Chemical Biology

Background:

  • Conditionally activated ("caged") oligonucleotides enable spatiotemporal control in biological research.
  • Applications include regulating in vivo gene expression and probing oligonucleotide targets.

Purpose of the Study:

  • To review recent advances in oligonucleotide caging strategies.
  • To highlight novel caging approaches for enhanced biological applications.

Main Methods:

  • Summarized recent developments in stimuli-responsive oligonucleotide caging.
  • Detailed the synthesis and application of circular caged oligonucleotides for gene regulation.
  • Described Transcriptome In Vivo Analysis (TIVA) using caged oligos for single-cell mRNA isolation.
  • Presented the development of the first protease-activated oligonucleotide probe for caspase-3.

Main Results:

  • Developed an efficient synthesis for circular caged oligonucleotides.
  • Demonstrated successful gene regulation using circular caged antisense DNA oligonucleotides.
  • Engineered TIVA probes with improved caging stability for mRNA isolation.
  • Created a protease-activated probe for caspase-3, enabling targeted transcriptome investigation.

Conclusions:

  • Oligo cyclization offers a simplified and stabilized approach to oligonucleotide caging.
  • TIVA technology with enhanced probes allows for detailed analysis of mRNA in living tissues.
  • Protease-activated probes expand the toolkit for studying specific physiological conditions, especially where light activation is not feasible.
Keywords:
caged oligonucleotidesenzyme activationtranscriptome in vivo analysis

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