Toolkit/designer cells engineered for gene switch-driven SEAP expression

designer cells engineered for gene switch-driven SEAP expression

Construct Pattern·Research·Since 2014

Also known as: designer cells, gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP)

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

Summary

This tool comprises designer mammalian cells engineered to express human placental secreted alkaline phosphatase (SEAP) under control of a benzoate-/vanillate-responsive mammalian gene switch. It functions as a small-molecule-regulated reporter system for monitoring inducible and repressible transgene expression in vitro and in implanted mice.

Usefulness & Problems

Why this is useful

The system is useful for reporting mammalian transgene control by food additive inputs, using secreted SEAP as an accessible output. The cited study also indicates that the benzoate-/vanillate-responsive device is compatible with other transgene control systems and can be incorporated into higher-order control networks.

Source:

we have designed different mammalian gene expression systems that could be induced and repressed by the food additives benzoate and vanillate

Source:

When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme.

Problem solved

This tool addresses the need for a mammalian reporter cell system that links externally supplied small molecules, specifically benzoate and vanillate, to controllable transgene expression. It also supports testing of dual-input antagonistic gene regulation in cultured cells and implanted-cell mouse settings.

Problem links

Need conditional recombination or state switching

Derived

This tool comprises designer mammalian cells engineered to express human placental secreted alkaline phosphatase (SEAP) under control of a benzoate-/vanillate-responsive mammalian gene switch. It functions as a small-molecule-regulated reporter system for monitoring inducible and repressible transgene expression in vitro and in implanted mice.

Taxonomy & Function

Primary hierarchy

Mechanism Branch

Architecture: A reusable architecture pattern for arranging parts into an engineered system.

Target processes

recombination

Implementation Constraints

cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationoperating role: reporter

The construct places human placental secreted alkaline phosphatase under control of a benzoate-/vanillate-responsive mammalian gene switch in designer mammalian cells. Practical use in the cited work included implantation of the engineered cells into mice and modulation of output through a benzoate-enriched drinking program. Additional implementation details are not available from the supplied evidence.

The provided evidence does not specify the exact switch architecture, promoter design, host cell line, or quantitative performance metrics such as dynamic range or response kinetics. Validation is described for SEAP reporting and implanted-mouse correlation, but broader benchmarking across cell types, payload genes, or long-term performance is not provided here.

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Observations

successMouseapplication demo

Inferred from claim c2 during normalization. In mice implanted with designer cells expressing SEAP under gene-switch control, blood SEAP levels directly correlated with a benzoate-enriched drinking program. Derived from claim c2. Quoted text: When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme.

Source:

successMouseapplication demo

Inferred from claim c2 during normalization. In mice implanted with designer cells expressing SEAP under gene-switch control, blood SEAP levels directly correlated with a benzoate-enriched drinking program. Derived from claim c2. Quoted text: When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme.

Source:

successMouseapplication demo

Inferred from claim c2 during normalization. In mice implanted with designer cells expressing SEAP under gene-switch control, blood SEAP levels directly correlated with a benzoate-enriched drinking program. Derived from claim c2. Quoted text: When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme.

Source:

successMouseapplication demo

Inferred from claim c2 during normalization. In mice implanted with designer cells expressing SEAP under gene-switch control, blood SEAP levels directly correlated with a benzoate-enriched drinking program. Derived from claim c2. Quoted text: When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme.

Source:

successMouseapplication demo

Inferred from claim c2 during normalization. In mice implanted with designer cells expressing SEAP under gene-switch control, blood SEAP levels directly correlated with a benzoate-enriched drinking program. Derived from claim c2. Quoted text: When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme.

Source:

successMouseapplication demo

Inferred from claim c2 during normalization. In mice implanted with designer cells expressing SEAP under gene-switch control, blood SEAP levels directly correlated with a benzoate-enriched drinking program. Derived from claim c2. Quoted text: When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme.

Source:

successMouseapplication demo

Inferred from claim c2 during normalization. In mice implanted with designer cells expressing SEAP under gene-switch control, blood SEAP levels directly correlated with a benzoate-enriched drinking program. Derived from claim c2. Quoted text: When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme.

Source:

Supporting Sources

Ranked Claims

Claim 1compatibilitysupports2014Source 1needs review

The benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks.

the benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks
Claim 2compatibilitysupports2014Source 1needs review

The benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks.

the benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks
Claim 3compatibilitysupports2014Source 1needs review

The benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks.

the benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks
Claim 4compatibilitysupports2014Source 1needs review

The benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks.

the benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks
Claim 5compatibilitysupports2014Source 1needs review

The benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks.

the benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks
Claim 6compatibilitysupports2014Source 1needs review

The benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks.

the benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks
Claim 7compatibilitysupports2014Source 1needs review

The benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks.

the benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks
Claim 8functional responsesupports2014Source 1needs review

The authors designed mammalian gene expression systems that can be induced and repressed by the food additives benzoate and vanillate.

we have designed different mammalian gene expression systems that could be induced and repressed by the food additives benzoate and vanillate
Claim 9functional responsesupports2014Source 1needs review

The authors designed mammalian gene expression systems that can be induced and repressed by the food additives benzoate and vanillate.

we have designed different mammalian gene expression systems that could be induced and repressed by the food additives benzoate and vanillate
Claim 10functional responsesupports2014Source 1needs review

The authors designed mammalian gene expression systems that can be induced and repressed by the food additives benzoate and vanillate.

we have designed different mammalian gene expression systems that could be induced and repressed by the food additives benzoate and vanillate
Claim 11functional responsesupports2014Source 1needs review

The authors designed mammalian gene expression systems that can be induced and repressed by the food additives benzoate and vanillate.

we have designed different mammalian gene expression systems that could be induced and repressed by the food additives benzoate and vanillate
Claim 12functional responsesupports2014Source 1needs review

The authors designed mammalian gene expression systems that can be induced and repressed by the food additives benzoate and vanillate.

we have designed different mammalian gene expression systems that could be induced and repressed by the food additives benzoate and vanillate
Claim 13functional responsesupports2014Source 1needs review

The authors designed mammalian gene expression systems that can be induced and repressed by the food additives benzoate and vanillate.

we have designed different mammalian gene expression systems that could be induced and repressed by the food additives benzoate and vanillate
Claim 14functional responsesupports2014Source 1needs review

The authors designed mammalian gene expression systems that can be induced and repressed by the food additives benzoate and vanillate.

we have designed different mammalian gene expression systems that could be induced and repressed by the food additives benzoate and vanillate
Claim 15in vivo responsesupports2014Source 1needs review

In mice implanted with designer cells expressing SEAP under gene-switch control, blood SEAP levels directly correlated with a benzoate-enriched drinking program.

When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme.
Claim 16in vivo responsesupports2014Source 1needs review

In mice implanted with designer cells expressing SEAP under gene-switch control, blood SEAP levels directly correlated with a benzoate-enriched drinking program.

When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme.
Claim 17in vivo responsesupports2014Source 1needs review

In mice implanted with designer cells expressing SEAP under gene-switch control, blood SEAP levels directly correlated with a benzoate-enriched drinking program.

When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme.
Claim 18in vivo responsesupports2014Source 1needs review

In mice implanted with designer cells expressing SEAP under gene-switch control, blood SEAP levels directly correlated with a benzoate-enriched drinking program.

When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme.
Claim 19in vivo responsesupports2014Source 1needs review

In mice implanted with designer cells expressing SEAP under gene-switch control, blood SEAP levels directly correlated with a benzoate-enriched drinking program.

When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme.
Claim 20in vivo responsesupports2014Source 1needs review

In mice implanted with designer cells expressing SEAP under gene-switch control, blood SEAP levels directly correlated with a benzoate-enriched drinking program.

When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme.
Claim 21in vivo responsesupports2014Source 1needs review

In mice implanted with designer cells expressing SEAP under gene-switch control, blood SEAP levels directly correlated with a benzoate-enriched drinking program.

When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme.
Claim 22network dynamicssupports2014Source 1needs review

Higher-order control networks assembled from the benzoate-/vanillate-responsive device provided expression dynamics reminiscent of a lap-timing stopwatch.

could be assembled into higher-order control networks providing expression dynamics reminiscent of a lap-timing stopwatch
Claim 23network dynamicssupports2014Source 1needs review

Higher-order control networks assembled from the benzoate-/vanillate-responsive device provided expression dynamics reminiscent of a lap-timing stopwatch.

could be assembled into higher-order control networks providing expression dynamics reminiscent of a lap-timing stopwatch
Claim 24network dynamicssupports2014Source 1needs review

Higher-order control networks assembled from the benzoate-/vanillate-responsive device provided expression dynamics reminiscent of a lap-timing stopwatch.

could be assembled into higher-order control networks providing expression dynamics reminiscent of a lap-timing stopwatch
Claim 25network dynamicssupports2014Source 1needs review

Higher-order control networks assembled from the benzoate-/vanillate-responsive device provided expression dynamics reminiscent of a lap-timing stopwatch.

could be assembled into higher-order control networks providing expression dynamics reminiscent of a lap-timing stopwatch
Claim 26network dynamicssupports2014Source 1needs review

Higher-order control networks assembled from the benzoate-/vanillate-responsive device provided expression dynamics reminiscent of a lap-timing stopwatch.

could be assembled into higher-order control networks providing expression dynamics reminiscent of a lap-timing stopwatch
Claim 27network dynamicssupports2014Source 1needs review

Higher-order control networks assembled from the benzoate-/vanillate-responsive device provided expression dynamics reminiscent of a lap-timing stopwatch.

could be assembled into higher-order control networks providing expression dynamics reminiscent of a lap-timing stopwatch
Claim 28network dynamicssupports2014Source 1needs review

Higher-order control networks assembled from the benzoate-/vanillate-responsive device provided expression dynamics reminiscent of a lap-timing stopwatch.

could be assembled into higher-order control networks providing expression dynamics reminiscent of a lap-timing stopwatch

Approval Evidence

1 source1 linked approval claimfirst-pass slug designer-cells-engineered-for-gene-switch-driven-seap-expression
designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP)

Source:

in vivo responsesupports

In mice implanted with designer cells expressing SEAP under gene-switch control, blood SEAP levels directly correlated with a benzoate-enriched drinking program.

When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme.

Source:

Comparisons

Source-backed strengths

The source reports that the gene expression system can be both induced and repressed by the food additives benzoate and vanillate. In implanted mice, blood SEAP levels directly correlated with a benzoate-enriched drinking program, providing in vivo functional validation. The device was also reported to be compatible with other transgene control systems and suitable for assembly into higher-order control networks.

designer cells engineered for gene switch-driven SEAP expression and cell-specific receptor subtype gene deletion mouse models address a similar problem space because they share recombination.

Shared frame: same top-level item type; shared target processes: recombination

Strengths here: looks easier to implement in practice.

Compared with eNpHR

designer cells engineered for gene switch-driven SEAP expression and eNpHR address a similar problem space because they share recombination.

Shared frame: same top-level item type; shared target processes: recombination

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

designer cells engineered for gene switch-driven SEAP expression and katA::mCherry replacement construct address a similar problem space because they share recombination.

Shared frame: same top-level item type; shared target processes: recombination

Ranked Citations

  1. 1.
    StructuralSource 1Nucleic Acids Research2014Claim 1Claim 2Claim 3

    Extracted from this source document.