Source 1primary paper2023Communications Chemistry
Toolkit/phosphorothioate-caged antisense oligonucleotides
phosphorothioate-caged antisense oligonucleotides
Also known as: photocaged antisense oligonucleotides, PS-caged antisense oligonucleotides
Taxonomy: Mechanism Branch / Component. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Phosphorothioate-caged antisense oligonucleotides are mixed-backbone antisense oligonucleotides in which phosphorothioate linkages are modified with 2-nitroveratryl photocages. In the caged state, these modifications suppress target RNA duplex formation and RNase H activity, and UV uncaging restores antisense function to enable light-controlled knockdown of cell-free protein synthesis.
Usefulness & Problems
Why this is useful
This tool provides optical control over antisense oligonucleotide activity, allowing RNA targeting to be switched on with UV light rather than being constitutively active. The reported utility is temporal regulation of knockdown in cell-free protein synthesis systems through light-gated restoration of duplex formation and RNase H-mediated activity.
Problem solved
It addresses the problem of how to keep antisense oligonucleotides inactive until a defined time point while preserving the ability to trigger RNA knockdown on demand. The cited work specifically solves this in the context of cell-free protein synthesis by using photocaged phosphorothioate linkages that block activity until UV exposure.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Component: A low-level RNA part used inside a larger architecture that realizes a mechanism.
Mechanisms
Conformational Uncaginglight-dependent uncaginglight-dependent uncaginglight-gated rnase h activationlight-gated rnase h activationPhotocleavagePhotocleavagesuppression and restoration of antisense duplex formationsuppression and restoration of antisense duplex formationTechniques
No technique tags yet.
Target processes
No target processes tagged yet.
Input: Light
Implementation Constraints
antisense based: Truecell free application: Truecofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: spectral hardware requirementlight controlled: Trueswitch architecture: uncaging
Implementation involves mixed-backbone antisense oligonucleotide design with phosphorothioate linkages bearing 2-nitroveratryl photocages. Activation requires UV uncaging, and the demonstrated use case is light-controlled knockdown in a cell-free protein synthesis context; no additional delivery, expression, or construct-format details are provided in the supplied evidence.
The supplied evidence is limited to a single 2023 study and specifically describes application in cell-free protein synthesis. No evidence is provided here for performance in living cells, tissue settings, alternative wavelengths, quantitative dynamic range, or independent replication.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Phosphorothioate-caged antisense oligonucleotides enable light-controlled knockdown of cell-free protein synthesis.
Accessible light-controlled knockdown of cell-free protein synthesis using phosphorothioate-caged antisense oligonucleotides
Phosphorothioate-caged antisense oligonucleotides enable light-controlled knockdown of cell-free protein synthesis.
Accessible light-controlled knockdown of cell-free protein synthesis using phosphorothioate-caged antisense oligonucleotides
Phosphorothioate-caged antisense oligonucleotides enable light-controlled knockdown of cell-free protein synthesis.
Accessible light-controlled knockdown of cell-free protein synthesis using phosphorothioate-caged antisense oligonucleotides
Phosphorothioate-caged antisense oligonucleotides enable light-controlled knockdown of cell-free protein synthesis.
Accessible light-controlled knockdown of cell-free protein synthesis using phosphorothioate-caged antisense oligonucleotides
Phosphorothioate-caged antisense oligonucleotides enable light-controlled knockdown of cell-free protein synthesis.
Accessible light-controlled knockdown of cell-free protein synthesis using phosphorothioate-caged antisense oligonucleotides
Installation of 2-nitroveratryl photocages onto phosphorothioate linkages in mixed-backbone antisense oligonucleotides suppresses duplex formation and RNase H activity until UV uncaging.
The PubMed/PMC record states the paper introduces a mild one-step chemoselective installation of 2-nitroveratryl photocages onto phosphorothioate linkages in mixed-backbone antisense oligonucleotides, suppressing duplex formation and RNase H activity until UV uncaging, and applies this to light-controlled knockdown in cell-free protein synthesis.
Installation of 2-nitroveratryl photocages onto phosphorothioate linkages in mixed-backbone antisense oligonucleotides suppresses duplex formation and RNase H activity until UV uncaging.
The PubMed/PMC record states the paper introduces a mild one-step chemoselective installation of 2-nitroveratryl photocages onto phosphorothioate linkages in mixed-backbone antisense oligonucleotides, suppressing duplex formation and RNase H activity until UV uncaging, and applies this to light-controlled knockdown in cell-free protein synthesis.
Installation of 2-nitroveratryl photocages onto phosphorothioate linkages in mixed-backbone antisense oligonucleotides suppresses duplex formation and RNase H activity until UV uncaging.
The PubMed/PMC record states the paper introduces a mild one-step chemoselective installation of 2-nitroveratryl photocages onto phosphorothioate linkages in mixed-backbone antisense oligonucleotides, suppressing duplex formation and RNase H activity until UV uncaging, and applies this to light-controlled knockdown in cell-free protein synthesis.
Installation of 2-nitroveratryl photocages onto phosphorothioate linkages in mixed-backbone antisense oligonucleotides suppresses duplex formation and RNase H activity until UV uncaging.
The PubMed/PMC record states the paper introduces a mild one-step chemoselective installation of 2-nitroveratryl photocages onto phosphorothioate linkages in mixed-backbone antisense oligonucleotides, suppressing duplex formation and RNase H activity until UV uncaging, and applies this to light-controlled knockdown in cell-free protein synthesis.
Installation of 2-nitroveratryl photocages onto phosphorothioate linkages in mixed-backbone antisense oligonucleotides suppresses duplex formation and RNase H activity until UV uncaging.
The PubMed/PMC record states the paper introduces a mild one-step chemoselective installation of 2-nitroveratryl photocages onto phosphorothioate linkages in mixed-backbone antisense oligonucleotides, suppressing duplex formation and RNase H activity until UV uncaging, and applies this to light-controlled knockdown in cell-free protein synthesis.
Approval Evidence
1 source2 linked approval claimsfirst-pass slug phosphorothioate-caged-antisense-oligonucleotides
Accessible light-controlled knockdown of cell-free protein synthesis using phosphorothioate-caged antisense oligonucleotides
Source:
applicationsupports
Phosphorothioate-caged antisense oligonucleotides enable light-controlled knockdown of cell-free protein synthesis.
Accessible light-controlled knockdown of cell-free protein synthesis using phosphorothioate-caged antisense oligonucleotides
Source:
mechanismsupports
Installation of 2-nitroveratryl photocages onto phosphorothioate linkages in mixed-backbone antisense oligonucleotides suppresses duplex formation and RNase H activity until UV uncaging.
The PubMed/PMC record states the paper introduces a mild one-step chemoselective installation of 2-nitroveratryl photocages onto phosphorothioate linkages in mixed-backbone antisense oligonucleotides, suppressing duplex formation and RNase H activity until UV uncaging, and applies this to light-controlled knockdown in cell-free protein synthesis.
Source:
Comparisons
Source-backed strengths
The key demonstrated strength is reversible optical gating of antisense function through a defined chemical modification: 2-nitroveratryl photocages on phosphorothioate linkages. The source reports suppression of both RNA duplex formation and RNase H activity in the dark state, followed by UV-enabled restoration sufficient for light-controlled knockdown of cell-free protein synthesis.
Ranked Citations
- 1.