Toolkit/blue light-responsive Cas13b mRNA knockdown system

blue light-responsive Cas13b mRNA knockdown system

RNA Element·Research·Since 2021

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

Summary

The blue light-responsive Cas13b mRNA knockdown system is an optogenetic RNA-control platform in which blue light induces expression of an engineered Cas13b that specifically degrades target mRNAs. In the reported application, combining three blue light-inducible switches reduced protein levels by more than 99%.

Usefulness & Problems

Why this is useful

This system is useful for light-triggered, sequence-specific post-transcriptional suppression of gene expression through targeted mRNA degradation. It addresses the need for optically controlled RNA knockdown using an engineered Cas13b effector rather than constitutive knockdown.

Source:

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.

Problem solved

It helps solve the problem of achieving inducible and specific mRNA knockdown with blue light as the input signal. The reported design links blue light-inducible gene expression to Cas13b-mediated target mRNA degradation.

Source:

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.

Problem links

Need conditional protein clearance

Derived

The blue light-responsive Cas13b mRNA knockdown system is an optogenetic RNA-control platform in which blue light induces expression of an engineered Cas13b that specifically degrades target mRNAs. In the reported application, combining three blue light-inducible switches reduced protein levels by more than 99%.

Need precise spatiotemporal control with light input

Derived

The blue light-responsive Cas13b mRNA knockdown system is an optogenetic RNA-control platform in which blue light induces expression of an engineered Cas13b that specifically degrades target mRNAs. In the reported application, combining three blue light-inducible switches reduced protein levels by more than 99%.

Need tighter control over gene expression timing or amplitude

Derived

The blue light-responsive Cas13b mRNA knockdown system is an optogenetic RNA-control platform in which blue light induces expression of an engineered Cas13b that specifically degrades target mRNAs. In the reported application, combining three blue light-inducible switches reduced protein levels by more than 99%.

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

degradationtranscription

Input: Light

Implementation Constraints

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

The system is described as relying on blue light-inducible expression of an engineered Cas13b, which then degrades target mRNAs specifically. The provided evidence does not specify the photoreceptor module, construct architecture, guide design, host system, or delivery method.

The supplied evidence does not provide details on target range, kinetics, reversibility, background activity in the dark, or performance across cell types and organisms. Independent replication and broad validation are not documented in the provided material.

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Supporting Sources

Ranked Claims

Claim 1application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %
Claim 2application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %
Claim 3application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %
Claim 4application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %
Claim 5application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %
Claim 6application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %
Claim 7application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %
Claim 8application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %
Claim 9application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %
Claim 10application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %
Claim 11application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %
Claim 12application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %
Claim 13application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %
Claim 14application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %
Claim 15application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %
Claim 16application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %
Claim 17application resultsupports2021Source 1needs review

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.
protein level reduction 99 %

Approval Evidence

1 source1 linked approval claimfirst-pass slug blue-light-responsive-cas13b-mrna-knockdown-system
the Zurbriggen group describes a blue light-responsive system for mRNA knockdown. The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically.

Source:

application resultsupports

A blue light-responsive engineered Cas13b system enables specific target mRNA degradation, and combining three blue light-inducible switches can reduce protein levels by more than 99%.

The system is based on the blue light-inducible expression of an engineered Cas13b to degrade target mRNAs specifically. By combining three blue light-inducible switches for mRNA degradation, suppressing transcription, and target protein destabilization, the protein levels can rapidly be reduced by >99%.

Source:

Comparisons

Source-backed strengths

The reported strength is specific target mRNA degradation mediated by an engineered Cas13b under blue light control. In the cited application, combining three blue light-inducible switches reduced protein levels by more than 99%, indicating strong functional suppression in that configuration.

Compared with CRY1

blue light-responsive Cas13b mRNA knockdown system and CRY1 address a similar problem space because they share degradation, transcription.

Shared frame: shared target processes: degradation, transcription; shared mechanisms: degradation; same primary input modality: light

Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.

Compared with Cry2

blue light-responsive Cas13b mRNA knockdown system and Cry2 address a similar problem space because they share degradation, transcription.

Shared frame: shared target processes: degradation, transcription; shared mechanisms: degradation; same primary input modality: light

Strengths here: looks easier to implement in practice; may avoid an exogenous cofactor requirement.

Relative tradeoffs: appears more independently replicated.

blue light-responsive Cas13b mRNA knockdown system and CRY2 and LOV-fused degron light-responsive repression/degradation system address a similar problem space because they share degradation, transcription.

Shared frame: shared target processes: degradation, transcription; shared mechanisms: degradation; same primary input modality: light

Strengths here: looks easier to implement in practice.

Ranked Citations

  1. 1.
    StructuralSource 1Advanced Biology2021Claim 12Claim 11Claim 11

    Extracted from this source document.