Source 1primary paper2025PPR
Toolkit/OptoLoop
OptoLoop
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
OptoLoop is an optogenetic multi-component switch for light-controlled manipulation of chromatin contacts. It is built from nuclease-dead Streptococcus pyogenes Cas9 fused to the light-inducible oligomerizing protein CRY2 and is reported to induce contacts between genomically distant repetitive DNA loci.
Usefulness & Problems
Why this is useful
OptoLoop is useful for experimentally perturbing genome organization with light in order to test functional consequences of induced chromatin looping. The available evidence indicates that it was used to analyze chromatin looping and nascent RNA production at individual alleles, providing evidence for looping-mediated repression of TERT.
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OptoLoop can drive induction of contacts between genomically distant repetitive DNA loci.
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OptoLoop allows direct manipulation of chromatin contacts by light in a controlled fashion.
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OptoLoop is based on a fusion between nuclease-dead SpCas9 and the light-inducible oligomerizing protein CRY2.
Source:
OptoLoop is a means to interrogate structure-function relationships in the genome at single-allele resolution.
Problem solved
OptoLoop addresses the problem of directly and reversibly inducing specific chromatin contacts to probe causal roles of 3D genome organization in gene regulation. The supplied evidence specifically supports its use in testing whether induced looping can repress TERT.
Source:
OptoLoop is a means to interrogate structure-function relationships in the genome at single-allele resolution.
Published Workflows
Objective: Develop and apply an optogenetic system to directly manipulate chromatin contacts and test how genome organization affects gene regulation.
Why it works: The workflow is based on fusing nuclease-dead SpCas9 to the light-inducible oligomerizing protein CRY2 so that light can be used to directly induce chromatin contacts at targeted loci.
light-inducible oligomerization-mediated chromatin contact formationDNA looping as a regulator of gene expressionoptogenetic perturbationCRISPR-based genomic targetingsingle-allele analysis of chromatin looping and nascent RNA production
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Mechanisms
crispr/dcas9-mediated genomic targetinglight-inducible oligomerizationOligomerizationtargeted chromatin contact inductionTechniques
No technique tags yet.
Target processes
No target processes tagged yet.
Input: Light
Implementation Constraints
OptoLoop is described as a fusion of nuclease-dead Streptococcus pyogenes Cas9 to CRY2, implying implementation through expression of a dSpCas9-CRY2 fusion and CRISPR-based targeting to repetitive genomic DNA loci. Light is the input modality, but the supplied evidence does not specify illumination wavelength, exposure regime, delivery format, or construct architecture beyond the fusion design.
The supplied evidence is limited to a single 2025 preprint and one summarized biological inference, so breadth of validation and independent replication are not established. Quantitative performance characteristics, reversibility kinetics, off-target effects, cell-type scope, and requirements for guide design are not provided in the evidence here.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Analysis of chromatin looping and nascent RNA production at individual alleles provided evidence for looping-mediated repression of TERT.
Analysis of chromatin looping and nascent RNA production at individual alleles provided evidence for looping-mediated repression of TERT.
Analysis of chromatin looping and nascent RNA production at individual alleles provided evidence for looping-mediated repression of TERT.
Analysis of chromatin looping and nascent RNA production at individual alleles provided evidence for looping-mediated repression of TERT.
Analysis of chromatin looping and nascent RNA production at individual alleles provided evidence for looping-mediated repression of TERT.
Analysis of chromatin looping and nascent RNA production at individual alleles provided evidence for looping-mediated repression of TERT.
Analysis of chromatin looping and nascent RNA production at individual alleles provided evidence for looping-mediated repression of TERT.
Analysis of chromatin looping and nascent RNA production at individual alleles provided evidence for looping-mediated repression of TERT.
OptoLoop can drive induction of contacts between genomically distant repetitive DNA loci.
OptoLoop can drive induction of contacts between genomically distant repetitive DNA loci.
OptoLoop can drive induction of contacts between genomically distant repetitive DNA loci.
OptoLoop can drive induction of contacts between genomically distant repetitive DNA loci.
OptoLoop can drive induction of contacts between genomically distant repetitive DNA loci.
OptoLoop can drive induction of contacts between genomically distant repetitive DNA loci.
OptoLoop can drive induction of contacts between genomically distant repetitive DNA loci.
OptoLoop can drive induction of contacts between genomically distant repetitive DNA loci.
OptoLoop allows direct manipulation of chromatin contacts by light in a controlled fashion.
OptoLoop allows direct manipulation of chromatin contacts by light in a controlled fashion.
OptoLoop allows direct manipulation of chromatin contacts by light in a controlled fashion.
OptoLoop allows direct manipulation of chromatin contacts by light in a controlled fashion.
OptoLoop allows direct manipulation of chromatin contacts by light in a controlled fashion.
OptoLoop allows direct manipulation of chromatin contacts by light in a controlled fashion.
OptoLoop allows direct manipulation of chromatin contacts by light in a controlled fashion.
OptoLoop allows direct manipulation of chromatin contacts by light in a controlled fashion.
OptoLoop is based on a fusion between nuclease-dead SpCas9 and the light-inducible oligomerizing protein CRY2.
OptoLoop is based on a fusion between nuclease-dead SpCas9 and the light-inducible oligomerizing protein CRY2.
OptoLoop is based on a fusion between nuclease-dead SpCas9 and the light-inducible oligomerizing protein CRY2.
OptoLoop is based on a fusion between nuclease-dead SpCas9 and the light-inducible oligomerizing protein CRY2.
OptoLoop is based on a fusion between nuclease-dead SpCas9 and the light-inducible oligomerizing protein CRY2.
OptoLoop is based on a fusion between nuclease-dead SpCas9 and the light-inducible oligomerizing protein CRY2.
OptoLoop is based on a fusion between nuclease-dead SpCas9 and the light-inducible oligomerizing protein CRY2.
OptoLoop is based on a fusion between nuclease-dead SpCas9 and the light-inducible oligomerizing protein CRY2.
OptoLoop is a means to interrogate structure-function relationships in the genome at single-allele resolution.
OptoLoop is a means to interrogate structure-function relationships in the genome at single-allele resolution.
OptoLoop is a means to interrogate structure-function relationships in the genome at single-allele resolution.
OptoLoop is a means to interrogate structure-function relationships in the genome at single-allele resolution.
OptoLoop is a means to interrogate structure-function relationships in the genome at single-allele resolution.
OptoLoop is a means to interrogate structure-function relationships in the genome at single-allele resolution.
OptoLoop is a means to interrogate structure-function relationships in the genome at single-allele resolution.
OptoLoop is a means to interrogate structure-function relationships in the genome at single-allele resolution.
Approval Evidence
1 source5 linked approval claimsfirst-pass slug optoloop
we have developed OptoLoop, an optogenetic system that allows direct manipulation of chromatin contacts by light in a controlled fashion. OptoLoop is based on the fusion between a nuclease-dead SpCas9 protein and the light-inducible oligomerizing protein CRY2.
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biological inferencesupports
Analysis of chromatin looping and nascent RNA production at individual alleles provided evidence for looping-mediated repression of TERT.
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functional effectsupports
OptoLoop can drive induction of contacts between genomically distant repetitive DNA loci.
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tool capabilitysupports
OptoLoop allows direct manipulation of chromatin contacts by light in a controlled fashion.
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tool compositionsupports
OptoLoop is based on a fusion between nuclease-dead SpCas9 and the light-inducible oligomerizing protein CRY2.
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use casesupports
OptoLoop is a means to interrogate structure-function relationships in the genome at single-allele resolution.
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Comparisons
Source-backed strengths
A key strength is the combination of CRISPR/dSpCas9 genomic targeting with light-inducible CRY2 oligomerization, enabling direct optical control over chromatin contact formation at targeted repetitive loci. The cited study reports allele-level analysis linking induced looping with nascent RNA output and supporting looping-mediated repression of TERT.
Ranked Citations
- 1.