Toolkit/photo-caged mRNA

photo-caged mRNA

RNA Element·Research·Since 2020

Also known as: photo-cages, photo-cages tethered to the 5′ untranslated region (5′-UTR) of an mRNA

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

Summary

Photo-caged mRNA is an mRNA engineering strategy in which small-molecule caging groups are tethered to the 5′ untranslated region to suppress translation until illumination. Photocleavage of the cages activates translation and enables single-cell spatiotemporal control in mammalian cells.

Usefulness & Problems

Why this is useful

This tool provides optical control over mRNA translation with single-cell spatial and temporal precision in mammalian cells. The cited study also shows that two distinct mRNAs can be sequentially activated in the same cell, supporting multiplexed control of gene expression.

Source:

we synthesized a pair of ‘photo-cages’ which can be selectively cleaved from mRNA upon photo-irradiation with different wavelengths of light. Sequential photo-activation of two mRNAs enabled precise optical control of translation of two unique transcripts.

Source:

We demonstrate sequential optical activation of two types of mRNAs in the same mammalian cell through the sequential photocleavage of small molecule caging groups (‘photo-cages’) tethered to the 5′ untranslated region (5′-UTR) of an mRNA.

Problem solved

Photo-caged mRNA addresses the problem of how to keep exogenous mRNA translationally silent until a defined time and place. It specifically solves the need for light-triggered, localized activation of translation from mRNA constructs in mammalian cells.

Problem links

Need precise spatiotemporal control with light input

Derived

Photo-caged mRNA is an mRNA engineering strategy in which small-molecule caging groups are tethered to the 5′ untranslated region to suppress translation until illumination. Photocleavage of the cages activates translation and enables single-cell spatiotemporal control in mammalian cells.

Need tighter control over protein production

Derived

Photo-caged mRNA is an mRNA engineering strategy in which small-molecule caging groups are tethered to the 5′ untranslated region to suppress translation until illumination. Photocleavage of the cages activates translation and enables single-cell spatiotemporal control in mammalian cells.

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

translation

Input: Light

Implementation Constraints

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

The defining construct feature is tethering small-molecule photo-cages to the 5′ untranslated region of an mRNA. The available evidence supports use in mammalian cells and sequential optical activation of two mRNA species, but it does not specify cage chemistries, illumination wavelengths, delivery methods, or expression workflows.

The supplied evidence is limited to a single 2020 study and does not provide quantitative performance metrics such as fold repression, activation kinetics, wavelength ranges, or phototoxicity. Evidence is also limited to mammalian cells, with no support here for in vivo use, broad organismal portability, or long-term expression studies.

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Supporting Sources

Ranked Claims

Claim 1mechanistic effectsupports2020Source 1needs review

Conjugation of photo-cages onto the 5′-UTR severely reduces mRNA translation.

Translation of mRNA was severely reduced upon conjugation of the ‘photo-cages’ onto the 5′-UTR.
Claim 2mechanistic effectsupports2020Source 1needs review

Conjugation of photo-cages onto the 5′-UTR severely reduces mRNA translation.

Translation of mRNA was severely reduced upon conjugation of the ‘photo-cages’ onto the 5′-UTR.
Claim 3mechanistic effectsupports2020Source 1needs review

Conjugation of photo-cages onto the 5′-UTR severely reduces mRNA translation.

Translation of mRNA was severely reduced upon conjugation of the ‘photo-cages’ onto the 5′-UTR.
Claim 4mechanistic effectsupports2020Source 1needs review

Conjugation of photo-cages onto the 5′-UTR severely reduces mRNA translation.

Translation of mRNA was severely reduced upon conjugation of the ‘photo-cages’ onto the 5′-UTR.
Claim 5mechanistic effectsupports2020Source 1needs review

Conjugation of photo-cages onto the 5′-UTR severely reduces mRNA translation.

Translation of mRNA was severely reduced upon conjugation of the ‘photo-cages’ onto the 5′-UTR.
Claim 6mechanistic effectsupports2020Source 1needs review

Conjugation of photo-cages onto the 5′-UTR severely reduces mRNA translation.

Translation of mRNA was severely reduced upon conjugation of the ‘photo-cages’ onto the 5′-UTR.
Claim 7mechanistic effectsupports2020Source 1needs review

Conjugation of photo-cages onto the 5′-UTR severely reduces mRNA translation.

Translation of mRNA was severely reduced upon conjugation of the ‘photo-cages’ onto the 5′-UTR.
Claim 8mechanistic effectsupports2020Source 1needs review

Photo-release of cages from mRNA triggers activation of translation with single-cell spatiotemporal resolution.

subsequent photo-release of the ‘cages’ from the mRNA transcript triggered activation of translation with single-cell spatiotemporal resolution
Claim 9mechanistic effectsupports2020Source 1needs review

Photo-release of cages from mRNA triggers activation of translation with single-cell spatiotemporal resolution.

subsequent photo-release of the ‘cages’ from the mRNA transcript triggered activation of translation with single-cell spatiotemporal resolution
Claim 10mechanistic effectsupports2020Source 1needs review

Photo-release of cages from mRNA triggers activation of translation with single-cell spatiotemporal resolution.

subsequent photo-release of the ‘cages’ from the mRNA transcript triggered activation of translation with single-cell spatiotemporal resolution
Claim 11mechanistic effectsupports2020Source 1needs review

Photo-release of cages from mRNA triggers activation of translation with single-cell spatiotemporal resolution.

subsequent photo-release of the ‘cages’ from the mRNA transcript triggered activation of translation with single-cell spatiotemporal resolution
Claim 12mechanistic effectsupports2020Source 1needs review

Photo-release of cages from mRNA triggers activation of translation with single-cell spatiotemporal resolution.

subsequent photo-release of the ‘cages’ from the mRNA transcript triggered activation of translation with single-cell spatiotemporal resolution
Claim 13mechanistic effectsupports2020Source 1needs review

Photo-release of cages from mRNA triggers activation of translation with single-cell spatiotemporal resolution.

subsequent photo-release of the ‘cages’ from the mRNA transcript triggered activation of translation with single-cell spatiotemporal resolution
Claim 14mechanistic effectsupports2020Source 1needs review

Photo-release of cages from mRNA triggers activation of translation with single-cell spatiotemporal resolution.

subsequent photo-release of the ‘cages’ from the mRNA transcript triggered activation of translation with single-cell spatiotemporal resolution
Claim 15method capabilitysupports2020Source 1needs review

A pair of photo-cages can be selectively cleaved from mRNA using different wavelengths of light to enable sequential photo-activation of two mRNAs.

we synthesized a pair of ‘photo-cages’ which can be selectively cleaved from mRNA upon photo-irradiation with different wavelengths of light. Sequential photo-activation of two mRNAs enabled precise optical control of translation of two unique transcripts.
Claim 16method capabilitysupports2020Source 1needs review

A pair of photo-cages can be selectively cleaved from mRNA using different wavelengths of light to enable sequential photo-activation of two mRNAs.

we synthesized a pair of ‘photo-cages’ which can be selectively cleaved from mRNA upon photo-irradiation with different wavelengths of light. Sequential photo-activation of two mRNAs enabled precise optical control of translation of two unique transcripts.
Claim 17method capabilitysupports2020Source 1needs review

A pair of photo-cages can be selectively cleaved from mRNA using different wavelengths of light to enable sequential photo-activation of two mRNAs.

we synthesized a pair of ‘photo-cages’ which can be selectively cleaved from mRNA upon photo-irradiation with different wavelengths of light. Sequential photo-activation of two mRNAs enabled precise optical control of translation of two unique transcripts.
Claim 18method capabilitysupports2020Source 1needs review

A pair of photo-cages can be selectively cleaved from mRNA using different wavelengths of light to enable sequential photo-activation of two mRNAs.

we synthesized a pair of ‘photo-cages’ which can be selectively cleaved from mRNA upon photo-irradiation with different wavelengths of light. Sequential photo-activation of two mRNAs enabled precise optical control of translation of two unique transcripts.
Claim 19method capabilitysupports2020Source 1needs review

A pair of photo-cages can be selectively cleaved from mRNA using different wavelengths of light to enable sequential photo-activation of two mRNAs.

we synthesized a pair of ‘photo-cages’ which can be selectively cleaved from mRNA upon photo-irradiation with different wavelengths of light. Sequential photo-activation of two mRNAs enabled precise optical control of translation of two unique transcripts.
Claim 20method capabilitysupports2020Source 1needs review

A pair of photo-cages can be selectively cleaved from mRNA using different wavelengths of light to enable sequential photo-activation of two mRNAs.

we synthesized a pair of ‘photo-cages’ which can be selectively cleaved from mRNA upon photo-irradiation with different wavelengths of light. Sequential photo-activation of two mRNAs enabled precise optical control of translation of two unique transcripts.
Claim 21method capabilitysupports2020Source 1needs review

A pair of photo-cages can be selectively cleaved from mRNA using different wavelengths of light to enable sequential photo-activation of two mRNAs.

we synthesized a pair of ‘photo-cages’ which can be selectively cleaved from mRNA upon photo-irradiation with different wavelengths of light. Sequential photo-activation of two mRNAs enabled precise optical control of translation of two unique transcripts.
Claim 22method capabilitysupports2020Source 1needs review

Two types of mRNAs can be sequentially optically activated in the same mammalian cell by sequential photocleavage of photo-cages tethered to the 5′-UTR.

We demonstrate sequential optical activation of two types of mRNAs in the same mammalian cell through the sequential photocleavage of small molecule caging groups (‘photo-cages’) tethered to the 5′ untranslated region (5′-UTR) of an mRNA.
Claim 23method capabilitysupports2020Source 1needs review

Two types of mRNAs can be sequentially optically activated in the same mammalian cell by sequential photocleavage of photo-cages tethered to the 5′-UTR.

We demonstrate sequential optical activation of two types of mRNAs in the same mammalian cell through the sequential photocleavage of small molecule caging groups (‘photo-cages’) tethered to the 5′ untranslated region (5′-UTR) of an mRNA.
Claim 24method capabilitysupports2020Source 1needs review

Two types of mRNAs can be sequentially optically activated in the same mammalian cell by sequential photocleavage of photo-cages tethered to the 5′-UTR.

We demonstrate sequential optical activation of two types of mRNAs in the same mammalian cell through the sequential photocleavage of small molecule caging groups (‘photo-cages’) tethered to the 5′ untranslated region (5′-UTR) of an mRNA.
Claim 25method capabilitysupports2020Source 1needs review

Two types of mRNAs can be sequentially optically activated in the same mammalian cell by sequential photocleavage of photo-cages tethered to the 5′-UTR.

We demonstrate sequential optical activation of two types of mRNAs in the same mammalian cell through the sequential photocleavage of small molecule caging groups (‘photo-cages’) tethered to the 5′ untranslated region (5′-UTR) of an mRNA.
Claim 26method capabilitysupports2020Source 1needs review

Two types of mRNAs can be sequentially optically activated in the same mammalian cell by sequential photocleavage of photo-cages tethered to the 5′-UTR.

We demonstrate sequential optical activation of two types of mRNAs in the same mammalian cell through the sequential photocleavage of small molecule caging groups (‘photo-cages’) tethered to the 5′ untranslated region (5′-UTR) of an mRNA.
Claim 27method capabilitysupports2020Source 1needs review

Two types of mRNAs can be sequentially optically activated in the same mammalian cell by sequential photocleavage of photo-cages tethered to the 5′-UTR.

We demonstrate sequential optical activation of two types of mRNAs in the same mammalian cell through the sequential photocleavage of small molecule caging groups (‘photo-cages’) tethered to the 5′ untranslated region (5′-UTR) of an mRNA.
Claim 28method capabilitysupports2020Source 1needs review

Two types of mRNAs can be sequentially optically activated in the same mammalian cell by sequential photocleavage of photo-cages tethered to the 5′-UTR.

We demonstrate sequential optical activation of two types of mRNAs in the same mammalian cell through the sequential photocleavage of small molecule caging groups (‘photo-cages’) tethered to the 5′ untranslated region (5′-UTR) of an mRNA.

Approval Evidence

1 source3 linked approval claimsfirst-pass slug photo-caged-mrna
small molecule caging groups (‘photo-cages’) tethered to the 5′ untranslated region (5′-UTR) of an mRNA

Source:

mechanistic effectsupports

Conjugation of photo-cages onto the 5′-UTR severely reduces mRNA translation.

Translation of mRNA was severely reduced upon conjugation of the ‘photo-cages’ onto the 5′-UTR.

Source:

mechanistic effectsupports

Photo-release of cages from mRNA triggers activation of translation with single-cell spatiotemporal resolution.

subsequent photo-release of the ‘cages’ from the mRNA transcript triggered activation of translation with single-cell spatiotemporal resolution

Source:

method capabilitysupports

Two types of mRNAs can be sequentially optically activated in the same mammalian cell by sequential photocleavage of photo-cages tethered to the 5′-UTR.

We demonstrate sequential optical activation of two types of mRNAs in the same mammalian cell through the sequential photocleavage of small molecule caging groups (‘photo-cages’) tethered to the 5′ untranslated region (5′-UTR) of an mRNA.

Source:

Comparisons

Source-backed strengths

Conjugation of photo-cages to the 5′-UTR severely reduces translation, indicating strong repression before illumination. Photo-release of the cages triggers translation activation with single-cell spatiotemporal resolution, and sequential optical activation of two mRNAs in the same mammalian cell was reported.

Compared with microRNA

photo-caged mRNA and microRNA address a similar problem space because they share translation.

Shared frame: same top-level item type; shared target processes: translation; shared mechanisms: translation_control; same primary input modality: light

Compared with PAL

photo-caged mRNA and PAL address a similar problem space because they share translation.

Shared frame: same top-level item type; shared target processes: translation; shared mechanisms: translation_control; same primary input modality: light

photo-caged mRNA and wavelength-selective photo-cage pair for mRNA address a similar problem space because they share translation.

Shared frame: same top-level item type; shared target processes: translation; shared mechanisms: photocleavage, translation control, translation_control; same primary input modality: light

Ranked Citations

  1. 1.

    Extracted from this source document.