Source 1primary paper2024MED
Toolkit/designed calcium-responsive transcription factor
designed calcium-responsive transcription factor
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Additionally, cells are engineered to express a designed calcium-responsive transcription factor controlling the expression of a selected therapeutic gene, constituting a therapeutic cellular device.
Usefulness & Problems
Why this is useful
This construct is described as a designed calcium-responsive transcription factor that controls expression of a selected therapeutic gene. It serves as the gene-regulatory core of the therapeutic cellular device.; linking ultrasound-induced calcium influx to therapeutic gene expression; building calcium-responsive engineered cell circuits
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This construct is described as a designed calcium-responsive transcription factor that controls expression of a selected therapeutic gene. It serves as the gene-regulatory core of the therapeutic cellular device.
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linking ultrasound-induced calcium influx to therapeutic gene expression
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building calcium-responsive engineered cell circuits
Problem solved
It solves the need to convert an intracellular calcium signal into programmable gene expression. In this paper, that enables acoustic control of a therapeutic output.; transducing calcium influx into controlled transcription of a therapeutic gene
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It solves the need to convert an intracellular calcium signal into programmable gene expression. In this paper, that enables acoustic control of a therapeutic output.
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transducing calcium influx into controlled transcription of a therapeutic gene
Problem links
transducing calcium influx into controlled transcription of a therapeutic gene
LiteratureIt solves the need to convert an intracellular calcium signal into programmable gene expression. In this paper, that enables acoustic control of a therapeutic output.
Source:
It solves the need to convert an intracellular calcium signal into programmable gene expression. In this paper, that enables acoustic control of a therapeutic output.
Published Workflows
Objective: Engineer a mammalian-cell therapeutic device that converts pulsed ultrasound stimulation into calcium-dependent therapeutic gene expression for localized in vivo treatment in deep tissue.
Why it works: The workflow couples pulsed-ultrasound-induced calcium influx to a designed calcium-responsive transcription factor so that an external acoustic input can drive therapeutic gene expression in engineered cells.
ultrasound-induced calcium influxcalcium-responsive transcriptional control of therapeutic gene expressionpulsed ultrasound stimulationmammalian cell engineering
Stages
- 1.Ultrasound parameter establishment for calcium influx(functional_characterization)
This stage establishes that pulsed ultrasound can generate the intracellular calcium signal needed to drive the downstream engineered transcriptional response.
Selection: Identify pulsed ultrasound parameters that induce calcium influx in HEK293 cells.
- 2.Engineering of calcium-responsive therapeutic cellular device(library_build)
This stage creates the cellular device that converts the established calcium signal into a therapeutic transcriptional output.
Selection: Engineer cells to express a designed calcium-responsive transcription factor controlling a therapeutic gene.
- 3.In vivo therapeutic demonstration in mice(in_vivo_validation)
This stage tests whether the engineered cellular device remains functional and therapeutically useful in a mouse disease context.
Selection: Demonstrate functionality of the engineered sonogenetic system in vivo and assess therapeutic benefit in acute colitis.
Steps
- 1.Establish pulsed ultrasound parameters that induce calcium influx in HEK293 cells
Define an acoustic input that reliably produces the calcium signal needed for downstream gene control.
The calcium influx response must be established before building or testing a calcium-responsive therapeutic circuit.
- 2.Engineer cells to express a designed calcium-responsive transcription factor controlling a therapeutic geneengineered regulatory module and resulting therapeutic cellular device
Convert the ultrasound-triggered calcium signal into controlled therapeutic gene expression.
This step follows parameter establishment because the circuit depends on calcium influx as its activating input.
- 3.Demonstrate in vivo function of the implanted anti-inflammatory cytokine-producing cellular device in a mouse acute colitis modelimplanted therapeutic cellular device
Test whether the engineered sonogenetic system can provide therapeutic benefit in vivo.
In vivo testing is performed after establishing the upstream calcium response and building the therapeutic circuit to assess full-system therapeutic function.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A reusable architecture pattern for arranging parts into an engineered system.
Techniques
Computational DesignTarget processes
transcriptionImplementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationoperating role: regulator
It requires engineered mammalian cells and an upstream stimulus that produces calcium influx. It also requires a linked therapeutic gene output cassette.; requires engineered expression in mammalian cells; depends on calcium influx as the upstream activating signal
The abstract does not show that this transcription factor alone provides ultrasound sensitivity; calcium influx is a separate upstream event. It also does not specify whether the design improves over other calcium-responsive transcription systems.; exact architecture is not specified in the provided evidence; specific response characteristics are not quantified in the abstract
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Pulsed ultrasound can be used to control calcium influx in mammalian cells.
This study uses pulsed ultrasound to control calcium influx in mammalian cells... Pulsed ultrasound parameters are established to induce calcium influx in HEK293 cells.
The engineered sonogenetic system enables acoustic control of a therapeutic cellular device in deep tissue without overexpressing calcium channels or gas vesicles.
engineers a therapeutic cellular device responsive to acoustic stimulation in deep tissue without overexpressing calcium channels or gas vesicles
A designed calcium-responsive transcription factor controls expression of a selected therapeutic gene in the engineered cellular device.
cells are engineered to express a designed calcium-responsive transcription factor controlling the expression of a selected therapeutic gene
In mice, an implanted anti-inflammatory cytokine-producing cellular device effectively alleviated acute colitis.
The engineered sonogenetic system's functionality is demonstrated in vivo in mice, where an implanted anti-inflammatory cytokine-producing cellular device effectively alleviates acute colitis, as shown by improved colonic morphology and histopathology.
Approval Evidence
1 source1 linked approval claimfirst-pass slug designed-calcium-responsive-transcription-factor
Additionally, cells are engineered to express a designed calcium-responsive transcription factor controlling the expression of a selected therapeutic gene, constituting a therapeutic cellular device.
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mechanism of actionsupports
A designed calcium-responsive transcription factor controls expression of a selected therapeutic gene in the engineered cellular device.
cells are engineered to express a designed calcium-responsive transcription factor controlling the expression of a selected therapeutic gene
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Comparisons
Source-backed strengths
provides a transcriptional interface between calcium signaling and therapeutic output
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provides a transcriptional interface between calcium signaling and therapeutic output
Compared with synthetic promoters
designed calcium-responsive transcription factor and synthetic promoters address a similar problem space because they share transcription.
Shared frame: same top-level item type; shared target processes: transcription
Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.
Compared with synthetic transcription factor
designed calcium-responsive transcription factor and synthetic transcription factor address a similar problem space because they share transcription.
Shared frame: same top-level item type; shared target processes: transcription
Compared with TALE-based chromatin loop engineering
designed calcium-responsive transcription factor and TALE-based chromatin loop engineering address a similar problem space because they share transcription.
Shared frame: same top-level item type; shared target processes: transcription
Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.
Ranked Citations
- 1.