Toolkit/photoactivatable cyclic caged morpholino oligomers

photoactivatable cyclic caged morpholino oligomers

RNA Element·Research·Since 2020

Also known as: caged antisense reagents, ccMOs

Taxonomy: Mechanism Branch / Component. Workflows sit above the mechanism and technique branches rather than replacing them.

Summary

Photoactivatable cyclic caged morpholino oligomers (ccMOs) are light-responsive antisense morpholino reagents engineered in a cyclic, caged format to suppress target binding until photoactivation. In the reported design, brief 405-nm illumination photocleaves the cage and restores antisense activity, enabling spatiotemporal regulation of gene expression.

Usefulness & Problems

Why this is useful

ccMOs are useful for modulating gene function with spatial and temporal precision in vivo. The light-gated design allows antisense activity to remain suppressed until illumination, supporting controlled perturbation of gene expression.

Source:

Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.

Source:

Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.

Problem solved

These reagents address the problem of achieving precise temporal and spatial control over morpholino-mediated gene regulation. The cyclic caging strategy specifically solves premature target binding by inhibiting DNA binding until light exposure restores activity.

Source:

Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.

Problem links

Need precise spatiotemporal control with light input

Derived

Photoactivatable cyclic caged morpholino oligomers (ccMOs) are light-responsive antisense morpholino reagents engineered in a cyclic, caged format to suppress target binding until photoactivation. In the reported design, brief 405-nm illumination photocleaves the cage and restores antisense activity, enabling spatiotemporal regulation of gene expression.

Taxonomy & Function

Primary hierarchy

Mechanism Branch

Component: A low-level RNA part used inside a larger architecture that realizes a mechanism.

Target processes

No target processes tagged yet.

Input: Light

Implementation Constraints

cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: spectral hardware requirementoperating role: actuatorswitch architecture: cleavage

The reported activation wavelength is 405 nm, and the construct uses a cyclic morpholino architecture with a photocleavable linker. An ethynyl-functionalized photocleavable linker was introduced to facilitate preparation, with click chemistry coupling and chemical linker engineering indicated by the source metadata.

The supplied evidence supports light-triggered activity control and synthetic improvement, but provides limited quantitative performance data. Independent replication, breadth across targets or organisms, and detailed in vivo validation outcomes are not established from the provided evidence.

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Supporting Sources

Ranked Claims

Claim 1activity controlsupports2020Source 1needs review

The caging strategy inhibits DNA binding ability and activity can be restored by brief illumination with 405-nm light.

HPLC analysis confirms that the caging strategy successfully inhibits the DNA binding ability, and the activity can be restored by brief illumination with 405-nm light.
activation wavelength 405 nm
Claim 2activity controlsupports2020Source 1needs review

The caging strategy inhibits DNA binding ability and activity can be restored by brief illumination with 405-nm light.

HPLC analysis confirms that the caging strategy successfully inhibits the DNA binding ability, and the activity can be restored by brief illumination with 405-nm light.
activation wavelength 405 nm
Claim 3activity controlsupports2020Source 1needs review

The caging strategy inhibits DNA binding ability and activity can be restored by brief illumination with 405-nm light.

HPLC analysis confirms that the caging strategy successfully inhibits the DNA binding ability, and the activity can be restored by brief illumination with 405-nm light.
activation wavelength 405 nm
Claim 4activity controlsupports2020Source 1needs review

The caging strategy inhibits DNA binding ability and activity can be restored by brief illumination with 405-nm light.

HPLC analysis confirms that the caging strategy successfully inhibits the DNA binding ability, and the activity can be restored by brief illumination with 405-nm light.
activation wavelength 405 nm
Claim 5activity controlsupports2020Source 1needs review

The caging strategy inhibits DNA binding ability and activity can be restored by brief illumination with 405-nm light.

HPLC analysis confirms that the caging strategy successfully inhibits the DNA binding ability, and the activity can be restored by brief illumination with 405-nm light.
activation wavelength 405 nm
Claim 6activity controlsupports2020Source 1needs review

The caging strategy inhibits DNA binding ability and activity can be restored by brief illumination with 405-nm light.

HPLC analysis confirms that the caging strategy successfully inhibits the DNA binding ability, and the activity can be restored by brief illumination with 405-nm light.
activation wavelength 405 nm
Claim 7activity controlsupports2020Source 1needs review

The caging strategy inhibits DNA binding ability and activity can be restored by brief illumination with 405-nm light.

HPLC analysis confirms that the caging strategy successfully inhibits the DNA binding ability, and the activity can be restored by brief illumination with 405-nm light.
activation wavelength 405 nm
Claim 8application potentialsupports2020Source 1needs review

These caged antisense reagents are presented as excellent tools to modulate gene function in vivo with spatial and temporal precision.

Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.
Claim 9application potentialsupports2020Source 1needs review

These caged antisense reagents are presented as excellent tools to modulate gene function in vivo with spatial and temporal precision.

Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.
Claim 10application potentialsupports2020Source 1needs review

These caged antisense reagents are presented as excellent tools to modulate gene function in vivo with spatial and temporal precision.

Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.
Claim 11application potentialsupports2020Source 1needs review

These caged antisense reagents are presented as excellent tools to modulate gene function in vivo with spatial and temporal precision.

Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.
Claim 12application potentialsupports2020Source 1needs review

These caged antisense reagents are presented as excellent tools to modulate gene function in vivo with spatial and temporal precision.

Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.
Claim 13application potentialsupports2020Source 1needs review

These caged antisense reagents are presented as excellent tools to modulate gene function in vivo with spatial and temporal precision.

Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.
Claim 14application potentialsupports2020Source 1needs review

These caged antisense reagents are presented as excellent tools to modulate gene function in vivo with spatial and temporal precision.

Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.
Claim 15design improvementsupports2020Source 1needs review

The novel ccMO design with an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.

We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation.
Claim 16design improvementsupports2020Source 1needs review

The novel ccMO design with an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.

We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation.
Claim 17design improvementsupports2020Source 1needs review

The novel ccMO design with an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.

We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation.
Claim 18design improvementsupports2020Source 1needs review

The novel ccMO design with an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.

We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation.
Claim 19design improvementsupports2020Source 1needs review

The novel ccMO design with an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.

We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation.
Claim 20design improvementsupports2020Source 1needs review

The novel ccMO design with an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.

We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation.
Claim 21design improvementsupports2020Source 1needs review

The novel ccMO design with an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.

We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation.
Claim 22synthetic advantagesupports2020Source 1needs review

Introducing an ethynyl function on the photocleavable linker facilitates Huisgen 1,3-dipolar cycloaddition coupling with the oligonucleotide and reduces synthetic steps while improving total yield and linker stability compared with previous strategies.

The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide. Compared to previous strategies, this modification reduces the number of synthetic steps and significantly improves the total yield and the stability of the linker.
Claim 23synthetic advantagesupports2020Source 1needs review

Introducing an ethynyl function on the photocleavable linker facilitates Huisgen 1,3-dipolar cycloaddition coupling with the oligonucleotide and reduces synthetic steps while improving total yield and linker stability compared with previous strategies.

The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide. Compared to previous strategies, this modification reduces the number of synthetic steps and significantly improves the total yield and the stability of the linker.
Claim 24synthetic advantagesupports2020Source 1needs review

Introducing an ethynyl function on the photocleavable linker facilitates Huisgen 1,3-dipolar cycloaddition coupling with the oligonucleotide and reduces synthetic steps while improving total yield and linker stability compared with previous strategies.

The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide. Compared to previous strategies, this modification reduces the number of synthetic steps and significantly improves the total yield and the stability of the linker.
Claim 25synthetic advantagesupports2020Source 1needs review

Introducing an ethynyl function on the photocleavable linker facilitates Huisgen 1,3-dipolar cycloaddition coupling with the oligonucleotide and reduces synthetic steps while improving total yield and linker stability compared with previous strategies.

The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide. Compared to previous strategies, this modification reduces the number of synthetic steps and significantly improves the total yield and the stability of the linker.
Claim 26synthetic advantagesupports2020Source 1needs review

Introducing an ethynyl function on the photocleavable linker facilitates Huisgen 1,3-dipolar cycloaddition coupling with the oligonucleotide and reduces synthetic steps while improving total yield and linker stability compared with previous strategies.

The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide. Compared to previous strategies, this modification reduces the number of synthetic steps and significantly improves the total yield and the stability of the linker.
Claim 27synthetic advantagesupports2020Source 1needs review

Introducing an ethynyl function on the photocleavable linker facilitates Huisgen 1,3-dipolar cycloaddition coupling with the oligonucleotide and reduces synthetic steps while improving total yield and linker stability compared with previous strategies.

The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide. Compared to previous strategies, this modification reduces the number of synthetic steps and significantly improves the total yield and the stability of the linker.
Claim 28synthetic advantagesupports2020Source 1needs review

Introducing an ethynyl function on the photocleavable linker facilitates Huisgen 1,3-dipolar cycloaddition coupling with the oligonucleotide and reduces synthetic steps while improving total yield and linker stability compared with previous strategies.

The key factor is the introduction of an ethynyl function on the photocleavable linker to facilitate the use of a Huisgen 1,3-dipolar cycloaddition for the coupling reaction with the oligonucleotide. Compared to previous strategies, this modification reduces the number of synthetic steps and significantly improves the total yield and the stability of the linker.
Claim 29tool capabilitysupports2020Source 1needs review

Photoactivatable cyclic caged morpholino oligomers can selectively regulate gene expression with spatiotemporal control.

Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.
Claim 30tool capabilitysupports2020Source 1needs review

Photoactivatable cyclic caged morpholino oligomers can selectively regulate gene expression with spatiotemporal control.

Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.
Claim 31tool capabilitysupports2020Source 1needs review

Photoactivatable cyclic caged morpholino oligomers can selectively regulate gene expression with spatiotemporal control.

Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.
Claim 32tool capabilitysupports2020Source 1needs review

Photoactivatable cyclic caged morpholino oligomers can selectively regulate gene expression with spatiotemporal control.

Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.
Claim 33tool capabilitysupports2020Source 1needs review

Photoactivatable cyclic caged morpholino oligomers can selectively regulate gene expression with spatiotemporal control.

Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.
Claim 34tool capabilitysupports2020Source 1needs review

Photoactivatable cyclic caged morpholino oligomers can selectively regulate gene expression with spatiotemporal control.

Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.
Claim 35tool capabilitysupports2020Source 1needs review

Photoactivatable cyclic caged morpholino oligomers can selectively regulate gene expression with spatiotemporal control.

Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.

Approval Evidence

1 source4 linked approval claimsfirst-pass slug photoactivatable-cyclic-caged-morpholino-oligomers
Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.

Source:

activity controlsupports

The caging strategy inhibits DNA binding ability and activity can be restored by brief illumination with 405-nm light.

HPLC analysis confirms that the caging strategy successfully inhibits the DNA binding ability, and the activity can be restored by brief illumination with 405-nm light.

Source:

application potentialsupports

These caged antisense reagents are presented as excellent tools to modulate gene function in vivo with spatial and temporal precision.

Overall, the straightforward preparation together with the clean and fast photochemistry make these caged antisense reagents excellent tools to modulate gene function in-vivo with spatial and temporal precision.

Source:

design improvementsupports

The novel ccMO design with an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.

We describe a novel ccMO design that overcomes many of the challenges and considerably expedites the synthetic preparation.

Source:

tool capabilitysupports

Photoactivatable cyclic caged morpholino oligomers can selectively regulate gene expression with spatiotemporal control.

Photoactivatable cyclic caged morpholino oligomers (ccMOs) represent a promising tool to selectively regulate gene expression with spatiotemporal control.

Source:

Comparisons

Source-backed strengths

The reported caging strategy inhibits DNA binding and antisense activity, and activity can be restored by brief 405-nm illumination. The 2020 Molecules report also states that an ethynyl-functionalized photocleavable linker expedites synthetic preparation and overcomes many preparation challenges.

photoactivatable cyclic caged morpholino oligomers and phosphorothioate-caged antisense oligonucleotides address a similar problem space.

Shared frame: same top-level item type; shared mechanisms: photocleavage; same primary input modality: light

photoactivatable cyclic caged morpholino oligomers and photo-sensitive circular gRNAs address a similar problem space.

Shared frame: same top-level item type; shared mechanisms: photocleavage; same primary input modality: light

photoactivatable cyclic caged morpholino oligomers and small interfering RNA with randomly incorporated photolabile groups address a similar problem space.

Shared frame: same top-level item type; shared mechanisms: photocleavage; same primary input modality: light

Ranked Citations

  1. 1.
    StructuralSource 1Molecules2020Claim 1Claim 2Claim 3

    Extracted from this source document.