Source 1primary paper2023Angewandte Chemie International Edition
Toolkit/enzyme-activatable antisense oligonucleotide
enzyme-activatable antisense oligonucleotide
Taxonomy: Mechanism Branch / Component. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
The enzyme-activatable antisense oligonucleotide is an engineered antisense component used within a nanosystem for gene regulation. Available evidence indicates that it is combined with an upconversion nanoparticle-based photodynamic system and a mitochondria localization signal in a remotely controlled therapeutic platform.
Usefulness & Problems
Why this is useful
This tool is useful as a modular gene-regulatory element that can be integrated into a multifunctional nanosystem. The cited study positions it within a platform intended for spatiotemporally specific gene regulation and combinational tumor therapy, but the specific performance contribution of the oligonucleotide itself is not detailed in the provided evidence.
Problem solved
The available evidence suggests that this tool helps enable controlled gene regulation within a composite nanosystem. It is specifically presented as part of a strategy for spatiotemporally specific regulation, although the exact biological bottleneck solved by the antisense design is not described in the supplied text.
Problem links
Need inducible protein relocalization or recruitment
DerivedThe enzyme-activatable antisense oligonucleotide is an engineered antisense component used within a nanosystem for gene regulation. Available evidence indicates that it is combined with an upconversion nanoparticle-based photodynamic system and a mitochondria localization signal in a remotely controlled therapeutic platform.
Need precise spatiotemporal control with light input
DerivedThe enzyme-activatable antisense oligonucleotide is an engineered antisense component used within a nanosystem for gene regulation. Available evidence indicates that it is combined with an upconversion nanoparticle-based photodynamic system and a mitochondria localization signal in a remotely controlled therapeutic platform.
Published Workflows
Objective: Develop a 980 nm NIR light-controlled nanosystem for combined tumor therapy that couples photodynamic mitochondrial damage with enzyme-activated gene regulation to improve spatiotemporal precision.
Why it works: The strategy is designed so that 980 nm NIR light triggers ROS generation from the UCNP-based photodynamic system, ROS induces APE1 translocation to mitochondria, and APE1 then cleaves AP-site-containing DNA to release functional strands for gene regulation. This couples externally controlled photodynamic activation with endogenous enzyme-responsive oligonucleotide activation.
NIR-triggered ROS generationAPE1 translocation from nucleus to mitochondriaAPE1 cleavage at AP sitesrelease of functional single strands for gene regulationmitochondrial damageupconversion nanoparticle-based photodynamic nanosystem designenzyme-activatable antisense oligonucleotide engineeringTPP surface functionalizationNIR light activation
Steps
- 1.Engineer an enzyme-activatable antisense oligonucleotideengineered oligonucleotide component within URMT
Create an antisense component that can be activated by enzyme cleavage for downstream gene regulation.
The activatable oligonucleotide provides the gene-regulation logic that is later coupled to the photodynamic nanosystem.
- 2.Combine the activatable antisense oligonucleotide with a UCNP-based photodynamic nanosystemassembled hybrid nanosystem
Integrate light-triggered photodynamic function with the enzyme-activatable gene-regulation component.
The photodynamic module is needed to generate ROS under NIR light, which is the upstream trigger for the enzyme-activation mechanism.
- 3.Surface functionalize the hybrid nanosystem with TPP for mitochondrial targetingmitochondria-targeted final nanoplatform
Add mitochondrial targeting capability to the hybrid nanosystem.
Mitochondrial targeting is added after hybrid system construction to localize photodynamic damage and align the platform with the intended mitochondrial mechanism.
- 4.Activate URMT with 980 nm NIR light to generate ROSlight-activated therapeutic nanosystem
Trigger the photodynamic function that initiates the downstream activation cascade.
ROS generation is the immediate upstream event that enables APE1 translocation and therefore must occur before enzyme-mediated strand release.
- 5.Use ROS-induced APE1 mitochondrial translocation and AP-site cleavage to release functional single strands for gene regulationenzyme-activated gene-regulation system
Convert the photodynamic trigger into gene-regulatory output through endogenous APE1 cleavage.
This step depends on prior ROS generation because the abstract states ROS induces APE1 translocation, which then enables AP-site cleavage and strand release.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Component: A low-level RNA part used inside a larger architecture that realizes a mechanism.
Techniques
No technique tags yet.
Target processes
localizationInput: Light
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: spectral hardware requirementoperating role: regulator
The tool is implemented as an engineered antisense oligonucleotide within a nanosystem assembled together with an upconversion nanoparticle-based photodynamic module and a mitochondria localization signal. The provided evidence does not specify oligonucleotide chemistry, nanoparticle composition, activation conditions, or delivery and expression requirements.
The supplied evidence is limited to composition-level description and does not report target genes, activating enzyme identity, sequence design, or experimental performance. Independent replication and breadth of validation cannot be established from the provided material.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
The nanosystem is built from an enzyme-activatable antisense oligonucleotide combined with an upconversion nanoparticle-based photodynamic system and a mitochondria localization signal.
The nanosystem is built by engineering of an enzyme‐activatable antisense oligonucleotide and further combination with an upconversion nanoparticle‐based photodynamic system and a mitochondria localization signal.
The nanosystem is built from an enzyme-activatable antisense oligonucleotide combined with an upconversion nanoparticle-based photodynamic system and a mitochondria localization signal.
The nanosystem is built by engineering of an enzyme‐activatable antisense oligonucleotide and further combination with an upconversion nanoparticle‐based photodynamic system and a mitochondria localization signal.
The nanosystem is built from an enzyme-activatable antisense oligonucleotide combined with an upconversion nanoparticle-based photodynamic system and a mitochondria localization signal.
The nanosystem is built by engineering of an enzyme‐activatable antisense oligonucleotide and further combination with an upconversion nanoparticle‐based photodynamic system and a mitochondria localization signal.
The nanosystem is built from an enzyme-activatable antisense oligonucleotide combined with an upconversion nanoparticle-based photodynamic system and a mitochondria localization signal.
The nanosystem is built by engineering of an enzyme‐activatable antisense oligonucleotide and further combination with an upconversion nanoparticle‐based photodynamic system and a mitochondria localization signal.
The nanosystem is built from an enzyme-activatable antisense oligonucleotide combined with an upconversion nanoparticle-based photodynamic system and a mitochondria localization signal.
The nanosystem is built by engineering of an enzyme‐activatable antisense oligonucleotide and further combination with an upconversion nanoparticle‐based photodynamic system and a mitochondria localization signal.
The nanosystem is built from an enzyme-activatable antisense oligonucleotide combined with an upconversion nanoparticle-based photodynamic system and a mitochondria localization signal.
The nanosystem is built by engineering of an enzyme‐activatable antisense oligonucleotide and further combination with an upconversion nanoparticle‐based photodynamic system and a mitochondria localization signal.
The nanosystem is built from an enzyme-activatable antisense oligonucleotide combined with an upconversion nanoparticle-based photodynamic system and a mitochondria localization signal.
The nanosystem is built by engineering of an enzyme‐activatable antisense oligonucleotide and further combination with an upconversion nanoparticle‐based photodynamic system and a mitochondria localization signal.
Approval Evidence
1 source1 linked approval claimfirst-pass slug enzyme-activatable-antisense-oligonucleotide
The nanosystem is built by engineering of an enzyme‐activatable antisense oligonucleotide
Source:
compositionsupports
The nanosystem is built from an enzyme-activatable antisense oligonucleotide combined with an upconversion nanoparticle-based photodynamic system and a mitochondria localization signal.
The nanosystem is built by engineering of an enzyme‐activatable antisense oligonucleotide and further combination with an upconversion nanoparticle‐based photodynamic system and a mitochondria localization signal.
Source:
Comparisons
Source-backed strengths
A clear strength is its incorporation into a modular nanosystem that also includes an upconversion nanoparticle-based photodynamic system and a mitochondria localization signal. The evidence supports engineered assembly and remote-control context, but does not provide quantitative data on activation, knockdown efficiency, or localization precision.
Compared with eNpHR
enzyme-activatable antisense oligonucleotide and eNpHR address a similar problem space because they share localization.
Shared frame: shared target processes: localization; same primary input modality: light
Strengths here: looks easier to implement in practice; may avoid an exogenous cofactor requirement.
Compared with optogenetic systems adapted to regulate gene expression
enzyme-activatable antisense oligonucleotide and optogenetic systems adapted to regulate gene expression address a similar problem space because they share localization.
Shared frame: shared target processes: localization; same primary input modality: light
Strengths here: looks easier to implement in practice.
Compared with RESOLFT
enzyme-activatable antisense oligonucleotide and RESOLFT address a similar problem space because they share localization.
Shared frame: shared target processes: localization; same primary input modality: light
Ranked Citations
- 1.