Toolkit/FUS-CRISPR(a/i)

FUS-CRISPR(a/i)

Multi-Component Switch·Research·Since 2023

Also known as: CRISPRee, FUS-CRISPR, FUS-CRISPRa, FUS-CRISPR(a/ee), FUS-CRISPR(a/i) toolbox, FUS-inducible CRISPR, FUS-inducible CRISPRa, FUS-inducible CRISPRi

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

Summary

FUS-CRISPR(a/i) is a focused-ultrasound-controllable CRISPR toolbox comprising CRISPRa, CRISPRi, and CRISPR systems that incorporate heat-sensitive genetic modules. It is designed to regulate genome and epigenome functions in live cells and animals with spatiotemporal control.

Usefulness & Problems

Why this is useful

This toolbox enables noninvasive spatiotemporal control of CRISPR-based genome and epigenome regulation by coupling focused ultrasound to heat-sensitive genetic modules. The reported application to tumor-cell telomeres indicates utility for controlling therapeutic gene-regulatory interventions in vivo.

Source:

We further targeted FUS-CRISPR to telomeres in tumor cells to induce telomere disruption, inhibiting tumor growth and enhancing tumor susceptibility to killing by chimeric antigen receptor (CAR)-T cells.

Source:

We demonstrated the capabilities of FUS-inducible CRISPRa, CRISPRi, and CRISPR (FUS-CRISPR(a/i)) to upregulate, repress, and knockout exogenous and/or endogenous genes, respectively, in different cell types.

Source:

FUS-CRISPR-mediated telomere disruption for tumor priming combined with CAR-T therapy demonstrated synergistic therapeutic effects in xenograft mouse models.

Problem solved

FUS-CRISPR(a/i) addresses the problem of controlling CRISPRa, CRISPRi, and related CRISPR functions in live cells and animals with spatial and temporal precision. The source specifically positions it as a way to regulate genome and epigenome functions through focused-ultrasound-triggered activation of heat-sensitive modules.

Source:

We further targeted FUS-CRISPR to telomeres in tumor cells to induce telomere disruption, inhibiting tumor growth and enhancing tumor susceptibility to killing by chimeric antigen receptor (CAR)-T cells.

Source:

FUS-CRISPR-mediated telomere disruption for tumor priming combined with CAR-T therapy demonstrated synergistic therapeutic effects in xenograft mouse models.

Published Workflows

Ultrasound Control of Genomic Regulatory Toolboxes for Cancer Immunotherapy.

2024

Objective: Engineer and apply focused-ultrasound-inducible CRISPR regulatory tools for noninvasive, localized genome and epigenome control in cancer immunotherapy.

Why it works: The abstract states that focused ultrasound can penetrate deep and induce localized hyperthermia for transgene activation, enabling noninvasive spatial and temporal control of CRISPR-based genome and epigenome modulation.

focused ultrasound-induced localized hyperthermia for transgene activationtelomere disruptioninduced antigen expression in tumour-cell training centerssynNotch-triggered CAR production against a universal tumour antigenfocused ultrasound controlinducible CRISPR engineeringAAV in vivo deliverysynNotch CAR-T cell activation

Stages

  1. 1.
    Engineering of FUS-inducible CRISPR toolbox(library_design)

    This stage establishes the core inducible CRISPR systems needed for downstream functional and therapeutic testing.

    Selection: Creation of inducible CRISPR-based tools controllable by focused ultrasound.

  2. 2.
    Functional demonstration of genome and epigenome modulation(functional_characterization)

    This stage verifies that the engineered ultrasound-inducible tools perform the intended regulatory functions before therapeutic deployment.

    Selection: Demonstration of FUS-inducible CRISPR, CRISPRa, and CRISPRee capabilities in modulating the genome and epigenome.

  3. 3.
    Tumour priming by FUS-CRISPR telomere disruption(secondary_characterization)

    This stage tests whether the genomic intervention creates a therapeutically useful tumour state for downstream cell therapy.

    Selection: Assessment of whether FUS-CRISPR-mediated telomere disruption primes solid tumours for CAR-T therapy.

  4. 4.
    In vivo AAV delivery and FUS-triggered training-center activation(in_vivo_validation)

    This stage validates that the inducible CRISPR system can be delivered in vivo and used to create localized tumour-cell training centers for downstream immunotherapy.

    Selection: In vivo delivery of FUS-CRISPR using AAVs followed by FUS-induced telomere disruption and induced antigen expression in a tumour-cell subpopulation.

Steps

  1. 1.
    Engineer inducible CRISPR-based tools controllable by focused ultrasoundengineered system

    Create CRISPR-based tools that can be activated noninvasively by focused ultrasound.

    The inducible toolbox must be built before its genome, epigenome, and therapeutic functions can be tested.

  2. 2.
    Demonstrate genome and epigenome modulation by FUS-inducible CRISPR systemsengineered system under test

    Verify that the ultrasound-inducible CRISPR toolbox can modulate genomic and epigenomic states.

    Functional capability is demonstrated after engineering and before therapeutic application to establish that the toolbox works as intended.

  3. 3.
    Apply FUS-CRISPR-mediated telomere disruption to prime solid tumours for CAR-T therapytherapeutic genomic intervention

    Test whether localized telomere disruption creates a tumour state more amenable to CAR-T therapy.

    After establishing core CRISPR functionality, the authors test a specific therapeutic mechanism relevant to cancer immunotherapy.

  4. 4.
    Deliver FUS-CRISPR in vivo using AAVsdelivered inducible CRISPR system and delivery harness

    Deploy the FUS-CRISPR system in vivo for localized tumour reprogramming.

    In vivo delivery is required before ultrasound-triggered tumour-cell reprogramming and downstream synNotch CAR-T activation can occur.

  5. 5.
    Use focused ultrasound to induce telomere disruption and antigen expression in a tumour-cell subpopulationinducible tumour-cell reprogramming system

    Generate localized tumour-cell training centers that can activate synNotch CAR-T cells.

    This follows in vivo delivery because the tumour cells must first contain the inducible CRISPR system before FUS can trigger localized reprogramming.

  6. 6.
    Activate synNotch CAR-T cells to produce CARs against a universal tumour antigen and kill neighboring tumour cellscell therapy responder

    Translate localized training-center induction into broader tumour-cell killing.

    synNotch CAR-T activation depends on prior creation of tumour-cell training centers expressing the induced antigen.

Taxonomy & Function

Primary hierarchy

Mechanism Branch

Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.

Techniques

No technique tags yet.

Target processes

editingrecombination

Implementation Constraints

Implementation requires heat-sensitive genetic modules integrated into CRISPRa, CRISPRi, or CRISPR constructs and activation by focused ultrasound. The available evidence states use in live cells and animals, but does not specify promoters, Cas effectors, delivery methods, thermal thresholds, or ultrasound parameters.

The supplied evidence does not provide construct-level details, quantitative performance metrics, or comparisons against alternative inducible CRISPR systems. Independent replication is not indicated, and validation evidence in the provided material is limited to the originating study and one highlighted tumor application.

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Supporting Sources

Ranked Claims

Claim 1application scopesupports2024Source 2needs review

The FUS-CRISPR(a/ee) toolbox allows noninvasive and spatiotemporal control of genomic and epigenomic reprogramming for cancer treatment.

The FUS-CRISPR(a/ee) toolbox hence allows the noninvasive and spatiotemporal control of genomic/epigenomic reprogramming for cancer treatment.
Claim 2capabilitysupports2024Source 2needs review

FUS-inducible CRISPR, CRISPRa, and CRISPRee were demonstrated to modulate the genome and epigenome.

We demonstrate the capabilities of FUS-inducible CRISPR, CRISPR activation (CRISPRa), and CRISPR epigenetic editor (CRISPRee) in modulating the genome and epigenome.
Claim 3capabilitysupports2024Source 2needs review

The authors engineered inducible CRISPR-based tools controllable by focused ultrasound for localized transgene activation.

Here, we engineer a set of inducible CRISPR-based tools controllable by focused ultrasound (FUS), which can penetrate deep and induce localized hyperthermia for transgene activation.
Claim 4delivery applicationsupports2024Source 2needs review

FUS-CRISPR was delivered in vivo using AAVs.

We further deliver FUS-CRISPR in vivo using adeno-associated viruses (AAVs)...
Claim 5therapeutic mechanismsupports2024Source 2needs review

FUS-CRISPR-mediated telomere disruption primes solid tumours for CAR-T cell therapy.

We show that FUS-CRISPR-mediated telomere disruption primes solid tumours for chimeric antigen receptor (CAR)-T cell therapy.
Claim 6therapeutic mechanismsupports2024Source 2needs review

FUS-induced telomere disruption and induced antigen expression in a tumour-cell subpopulation can create training centers that activate synNotch CAR-T cells to produce CARs against a universal tumour antigen and kill neighboring tumour cells.

followed by FUS-induced telomere disruption and the expression of a clinically validated antigen in a subpopulation of tumour cells, functioning as "training centers" to activate synthetic Notch (synNotch) CAR-T cells to produce CARs against a universal tumour antigen to exterminate neighboring tumour cells.
Claim 7application effectsupports2023Source 1needs review

Targeting FUS-CRISPR to telomeres in tumor cells induced telomere disruption, inhibited tumor growth, and enhanced tumor susceptibility to CAR-T-cell killing.

We further targeted FUS-CRISPR to telomeres in tumor cells to induce telomere disruption, inhibiting tumor growth and enhancing tumor susceptibility to killing by chimeric antigen receptor (CAR)-T cells.
Claim 8application effectsupports2023Source 1needs review

Targeting FUS-CRISPR to telomeres in tumor cells induced telomere disruption, inhibited tumor growth, and enhanced tumor susceptibility to CAR-T-cell killing.

We further targeted FUS-CRISPR to telomeres in tumor cells to induce telomere disruption, inhibiting tumor growth and enhancing tumor susceptibility to killing by chimeric antigen receptor (CAR)-T cells.
Claim 9application effectsupports2023Source 1needs review

Targeting FUS-CRISPR to telomeres in tumor cells induced telomere disruption, inhibited tumor growth, and enhanced tumor susceptibility to CAR-T-cell killing.

We further targeted FUS-CRISPR to telomeres in tumor cells to induce telomere disruption, inhibiting tumor growth and enhancing tumor susceptibility to killing by chimeric antigen receptor (CAR)-T cells.
Claim 10application effectsupports2023Source 1needs review

Targeting FUS-CRISPR to telomeres in tumor cells induced telomere disruption, inhibited tumor growth, and enhanced tumor susceptibility to CAR-T-cell killing.

We further targeted FUS-CRISPR to telomeres in tumor cells to induce telomere disruption, inhibiting tumor growth and enhancing tumor susceptibility to killing by chimeric antigen receptor (CAR)-T cells.
Claim 11application effectsupports2023Source 1needs review

Targeting FUS-CRISPR to telomeres in tumor cells induced telomere disruption, inhibited tumor growth, and enhanced tumor susceptibility to CAR-T-cell killing.

We further targeted FUS-CRISPR to telomeres in tumor cells to induce telomere disruption, inhibiting tumor growth and enhancing tumor susceptibility to killing by chimeric antigen receptor (CAR)-T cells.
Claim 12application effectsupports2023Source 1needs review

Targeting FUS-CRISPR to telomeres in tumor cells induced telomere disruption, inhibited tumor growth, and enhanced tumor susceptibility to CAR-T-cell killing.

We further targeted FUS-CRISPR to telomeres in tumor cells to induce telomere disruption, inhibiting tumor growth and enhancing tumor susceptibility to killing by chimeric antigen receptor (CAR)-T cells.
Claim 13application effectsupports2023Source 1needs review

Targeting FUS-CRISPR to telomeres in tumor cells induced telomere disruption, inhibited tumor growth, and enhanced tumor susceptibility to CAR-T-cell killing.

We further targeted FUS-CRISPR to telomeres in tumor cells to induce telomere disruption, inhibiting tumor growth and enhancing tumor susceptibility to killing by chimeric antigen receptor (CAR)-T cells.
Claim 14engineeringsupports2023Source 1needs review

The authors engineered FUS-controllable CRISPRa, CRISPRi, and CRISPR tools containing heat-sensitive genetic modules for regulation of genome and epigenome in live cells and animals.

Here we engineer a set of CRISPR(a/i) tools containing heat-sensitive genetic modules controllable by FUS for the regulation of genome and epigenome in live cells and animals.
Claim 15engineeringsupports2023Source 1needs review

The authors engineered FUS-controllable CRISPRa, CRISPRi, and CRISPR tools containing heat-sensitive genetic modules for regulation of genome and epigenome in live cells and animals.

Here we engineer a set of CRISPR(a/i) tools containing heat-sensitive genetic modules controllable by FUS for the regulation of genome and epigenome in live cells and animals.
Claim 16engineeringsupports2023Source 1needs review

The authors engineered FUS-controllable CRISPRa, CRISPRi, and CRISPR tools containing heat-sensitive genetic modules for regulation of genome and epigenome in live cells and animals.

Here we engineer a set of CRISPR(a/i) tools containing heat-sensitive genetic modules controllable by FUS for the regulation of genome and epigenome in live cells and animals.
Claim 17engineeringsupports2023Source 1needs review

The authors engineered FUS-controllable CRISPRa, CRISPRi, and CRISPR tools containing heat-sensitive genetic modules for regulation of genome and epigenome in live cells and animals.

Here we engineer a set of CRISPR(a/i) tools containing heat-sensitive genetic modules controllable by FUS for the regulation of genome and epigenome in live cells and animals.
Claim 18engineeringsupports2023Source 1needs review

The authors engineered FUS-controllable CRISPRa, CRISPRi, and CRISPR tools containing heat-sensitive genetic modules for regulation of genome and epigenome in live cells and animals.

Here we engineer a set of CRISPR(a/i) tools containing heat-sensitive genetic modules controllable by FUS for the regulation of genome and epigenome in live cells and animals.
Claim 19engineeringsupports2023Source 1needs review

The authors engineered FUS-controllable CRISPRa, CRISPRi, and CRISPR tools containing heat-sensitive genetic modules for regulation of genome and epigenome in live cells and animals.

Here we engineer a set of CRISPR(a/i) tools containing heat-sensitive genetic modules controllable by FUS for the regulation of genome and epigenome in live cells and animals.
Claim 20engineeringsupports2023Source 1needs review

The authors engineered FUS-controllable CRISPRa, CRISPRi, and CRISPR tools containing heat-sensitive genetic modules for regulation of genome and epigenome in live cells and animals.

Here we engineer a set of CRISPR(a/i) tools containing heat-sensitive genetic modules controllable by FUS for the regulation of genome and epigenome in live cells and animals.
Claim 21functional capabilitysupports2023Source 1needs review

FUS-CRISPR(a/i) can upregulate, repress, and knock out exogenous and/or endogenous genes in different cell types.

We demonstrated the capabilities of FUS-inducible CRISPRa, CRISPRi, and CRISPR (FUS-CRISPR(a/i)) to upregulate, repress, and knockout exogenous and/or endogenous genes, respectively, in different cell types.
Claim 22functional capabilitysupports2023Source 1needs review

FUS-CRISPR(a/i) can upregulate, repress, and knock out exogenous and/or endogenous genes in different cell types.

We demonstrated the capabilities of FUS-inducible CRISPRa, CRISPRi, and CRISPR (FUS-CRISPR(a/i)) to upregulate, repress, and knockout exogenous and/or endogenous genes, respectively, in different cell types.
Claim 23functional capabilitysupports2023Source 1needs review

FUS-CRISPR(a/i) can upregulate, repress, and knock out exogenous and/or endogenous genes in different cell types.

We demonstrated the capabilities of FUS-inducible CRISPRa, CRISPRi, and CRISPR (FUS-CRISPR(a/i)) to upregulate, repress, and knockout exogenous and/or endogenous genes, respectively, in different cell types.
Claim 24functional capabilitysupports2023Source 1needs review

FUS-CRISPR(a/i) can upregulate, repress, and knock out exogenous and/or endogenous genes in different cell types.

We demonstrated the capabilities of FUS-inducible CRISPRa, CRISPRi, and CRISPR (FUS-CRISPR(a/i)) to upregulate, repress, and knockout exogenous and/or endogenous genes, respectively, in different cell types.
Claim 25functional capabilitysupports2023Source 1needs review

FUS-CRISPR(a/i) can upregulate, repress, and knock out exogenous and/or endogenous genes in different cell types.

We demonstrated the capabilities of FUS-inducible CRISPRa, CRISPRi, and CRISPR (FUS-CRISPR(a/i)) to upregulate, repress, and knockout exogenous and/or endogenous genes, respectively, in different cell types.
Claim 26functional capabilitysupports2023Source 1needs review

FUS-CRISPR(a/i) can upregulate, repress, and knock out exogenous and/or endogenous genes in different cell types.

We demonstrated the capabilities of FUS-inducible CRISPRa, CRISPRi, and CRISPR (FUS-CRISPR(a/i)) to upregulate, repress, and knockout exogenous and/or endogenous genes, respectively, in different cell types.
Claim 27functional capabilitysupports2023Source 1needs review

FUS-CRISPR(a/i) can upregulate, repress, and knock out exogenous and/or endogenous genes in different cell types.

We demonstrated the capabilities of FUS-inducible CRISPRa, CRISPRi, and CRISPR (FUS-CRISPR(a/i)) to upregulate, repress, and knockout exogenous and/or endogenous genes, respectively, in different cell types.
Claim 28platform capabilitysupports2023Source 1needs review

The FUS-CRISPR(a/i) toolbox enables remote, noninvasive, and spatiotemporal control of genomic and epigenomic reprogramming in vivo.

The FUS-CRISPR(a/i) toolbox allows the remote, noninvasive, and spatiotemporal control of genomic and epigenomic reprogramming in vivo, with extended applications in cancer treatment.
Claim 29platform capabilitysupports2023Source 1needs review

The FUS-CRISPR(a/i) toolbox enables remote, noninvasive, and spatiotemporal control of genomic and epigenomic reprogramming in vivo.

The FUS-CRISPR(a/i) toolbox allows the remote, noninvasive, and spatiotemporal control of genomic and epigenomic reprogramming in vivo, with extended applications in cancer treatment.
Claim 30platform capabilitysupports2023Source 1needs review

The FUS-CRISPR(a/i) toolbox enables remote, noninvasive, and spatiotemporal control of genomic and epigenomic reprogramming in vivo.

The FUS-CRISPR(a/i) toolbox allows the remote, noninvasive, and spatiotemporal control of genomic and epigenomic reprogramming in vivo, with extended applications in cancer treatment.
Claim 31platform capabilitysupports2023Source 1needs review

The FUS-CRISPR(a/i) toolbox enables remote, noninvasive, and spatiotemporal control of genomic and epigenomic reprogramming in vivo.

The FUS-CRISPR(a/i) toolbox allows the remote, noninvasive, and spatiotemporal control of genomic and epigenomic reprogramming in vivo, with extended applications in cancer treatment.
Claim 32platform capabilitysupports2023Source 1needs review

The FUS-CRISPR(a/i) toolbox enables remote, noninvasive, and spatiotemporal control of genomic and epigenomic reprogramming in vivo.

The FUS-CRISPR(a/i) toolbox allows the remote, noninvasive, and spatiotemporal control of genomic and epigenomic reprogramming in vivo, with extended applications in cancer treatment.
Claim 33platform capabilitysupports2023Source 1needs review

The FUS-CRISPR(a/i) toolbox enables remote, noninvasive, and spatiotemporal control of genomic and epigenomic reprogramming in vivo.

The FUS-CRISPR(a/i) toolbox allows the remote, noninvasive, and spatiotemporal control of genomic and epigenomic reprogramming in vivo, with extended applications in cancer treatment.
Claim 34platform capabilitysupports2023Source 1needs review

The FUS-CRISPR(a/i) toolbox enables remote, noninvasive, and spatiotemporal control of genomic and epigenomic reprogramming in vivo.

The FUS-CRISPR(a/i) toolbox allows the remote, noninvasive, and spatiotemporal control of genomic and epigenomic reprogramming in vivo, with extended applications in cancer treatment.
Claim 35therapeutic combinationsupports2023Source 1needs review

FUS-CRISPR-mediated telomere disruption combined with CAR-T therapy showed synergistic therapeutic effects in xenograft mouse models.

FUS-CRISPR-mediated telomere disruption for tumor priming combined with CAR-T therapy demonstrated synergistic therapeutic effects in xenograft mouse models.
Claim 36therapeutic combinationsupports2023Source 1needs review

FUS-CRISPR-mediated telomere disruption combined with CAR-T therapy showed synergistic therapeutic effects in xenograft mouse models.

FUS-CRISPR-mediated telomere disruption for tumor priming combined with CAR-T therapy demonstrated synergistic therapeutic effects in xenograft mouse models.
Claim 37therapeutic combinationsupports2023Source 1needs review

FUS-CRISPR-mediated telomere disruption combined with CAR-T therapy showed synergistic therapeutic effects in xenograft mouse models.

FUS-CRISPR-mediated telomere disruption for tumor priming combined with CAR-T therapy demonstrated synergistic therapeutic effects in xenograft mouse models.
Claim 38therapeutic combinationsupports2023Source 1needs review

FUS-CRISPR-mediated telomere disruption combined with CAR-T therapy showed synergistic therapeutic effects in xenograft mouse models.

FUS-CRISPR-mediated telomere disruption for tumor priming combined with CAR-T therapy demonstrated synergistic therapeutic effects in xenograft mouse models.
Claim 39therapeutic combinationsupports2023Source 1needs review

FUS-CRISPR-mediated telomere disruption combined with CAR-T therapy showed synergistic therapeutic effects in xenograft mouse models.

FUS-CRISPR-mediated telomere disruption for tumor priming combined with CAR-T therapy demonstrated synergistic therapeutic effects in xenograft mouse models.
Claim 40therapeutic combinationsupports2023Source 1needs review

FUS-CRISPR-mediated telomere disruption combined with CAR-T therapy showed synergistic therapeutic effects in xenograft mouse models.

FUS-CRISPR-mediated telomere disruption for tumor priming combined with CAR-T therapy demonstrated synergistic therapeutic effects in xenograft mouse models.
Claim 41therapeutic combinationsupports2023Source 1needs review

FUS-CRISPR-mediated telomere disruption combined with CAR-T therapy showed synergistic therapeutic effects in xenograft mouse models.

FUS-CRISPR-mediated telomere disruption for tumor priming combined with CAR-T therapy demonstrated synergistic therapeutic effects in xenograft mouse models.

Approval Evidence

2 sources11 linked approval claimsfirst-pass slugs fus-crispr-a-ee-toolbox, fus-crispr-a-i
Here, we engineer a set of inducible CRISPR-based tools controllable by focused ultrasound (FUS)... We demonstrate the capabilities of FUS-inducible CRISPR, CRISPR activation (CRISPRa), and CRISPR epigenetic editor (CRISPRee)... The FUS-CRISPR(a/ee) toolbox hence allows the noninvasive and spatiotemporal control of genomic/epigenomic reprogramming for cancer treatment.

Source:

Here we engineer a set of CRISPR(a/i) tools containing heat-sensitive genetic modules controllable by FUS for the regulation of genome and epigenome in live cells and animals.

Source:

application scopesupports

The FUS-CRISPR(a/ee) toolbox allows noninvasive and spatiotemporal control of genomic and epigenomic reprogramming for cancer treatment.

The FUS-CRISPR(a/ee) toolbox hence allows the noninvasive and spatiotemporal control of genomic/epigenomic reprogramming for cancer treatment.

Source:

capabilitysupports

FUS-inducible CRISPR, CRISPRa, and CRISPRee were demonstrated to modulate the genome and epigenome.

We demonstrate the capabilities of FUS-inducible CRISPR, CRISPR activation (CRISPRa), and CRISPR epigenetic editor (CRISPRee) in modulating the genome and epigenome.

Source:

capabilitysupports

The authors engineered inducible CRISPR-based tools controllable by focused ultrasound for localized transgene activation.

Here, we engineer a set of inducible CRISPR-based tools controllable by focused ultrasound (FUS), which can penetrate deep and induce localized hyperthermia for transgene activation.

Source:

delivery applicationsupports

FUS-CRISPR was delivered in vivo using AAVs.

We further deliver FUS-CRISPR in vivo using adeno-associated viruses (AAVs)...

Source:

therapeutic mechanismsupports

FUS-CRISPR-mediated telomere disruption primes solid tumours for CAR-T cell therapy.

We show that FUS-CRISPR-mediated telomere disruption primes solid tumours for chimeric antigen receptor (CAR)-T cell therapy.

Source:

therapeutic mechanismsupports

FUS-induced telomere disruption and induced antigen expression in a tumour-cell subpopulation can create training centers that activate synNotch CAR-T cells to produce CARs against a universal tumour antigen and kill neighboring tumour cells.

followed by FUS-induced telomere disruption and the expression of a clinically validated antigen in a subpopulation of tumour cells, functioning as "training centers" to activate synthetic Notch (synNotch) CAR-T cells to produce CARs against a universal tumour antigen to exterminate neighboring tumour cells.

Source:

application effectsupports

Targeting FUS-CRISPR to telomeres in tumor cells induced telomere disruption, inhibited tumor growth, and enhanced tumor susceptibility to CAR-T-cell killing.

We further targeted FUS-CRISPR to telomeres in tumor cells to induce telomere disruption, inhibiting tumor growth and enhancing tumor susceptibility to killing by chimeric antigen receptor (CAR)-T cells.

Source:

engineeringsupports

The authors engineered FUS-controllable CRISPRa, CRISPRi, and CRISPR tools containing heat-sensitive genetic modules for regulation of genome and epigenome in live cells and animals.

Here we engineer a set of CRISPR(a/i) tools containing heat-sensitive genetic modules controllable by FUS for the regulation of genome and epigenome in live cells and animals.

Source:

functional capabilitysupports

FUS-CRISPR(a/i) can upregulate, repress, and knock out exogenous and/or endogenous genes in different cell types.

We demonstrated the capabilities of FUS-inducible CRISPRa, CRISPRi, and CRISPR (FUS-CRISPR(a/i)) to upregulate, repress, and knockout exogenous and/or endogenous genes, respectively, in different cell types.

Source:

platform capabilitysupports

The FUS-CRISPR(a/i) toolbox enables remote, noninvasive, and spatiotemporal control of genomic and epigenomic reprogramming in vivo.

The FUS-CRISPR(a/i) toolbox allows the remote, noninvasive, and spatiotemporal control of genomic and epigenomic reprogramming in vivo, with extended applications in cancer treatment.

Source:

therapeutic combinationsupports

FUS-CRISPR-mediated telomere disruption combined with CAR-T therapy showed synergistic therapeutic effects in xenograft mouse models.

FUS-CRISPR-mediated telomere disruption for tumor priming combined with CAR-T therapy demonstrated synergistic therapeutic effects in xenograft mouse models.

Source:

Comparisons

Source-backed strengths

The system was engineered as a toolbox spanning CRISPRa, CRISPRi, and CRISPR modalities rather than a single construct class. In the reported application, targeting the system to telomeres in tumor cells induced telomere disruption, inhibited tumor growth, and increased susceptibility to CAR-T-cell killing.

Source:

Here we engineer a set of CRISPR(a/i) tools containing heat-sensitive genetic modules controllable by FUS for the regulation of genome and epigenome in live cells and animals.

Ranked Citations

  1. 1.
    StructuralSource 12023Claim 7Claim 8Claim 9

    Seeded from load plan for claim c4. Extracted from this source document.

  2. 2.
    StructuralSource 2MED2024Claim 1Claim 2Claim 3

    Seeded from load plan for claim c3. Extracted from this source document.