Toolkit/benzoate-/vanillate-responsive mammalian gene switch

benzoate-/vanillate-responsive mammalian gene switch

Multi-Component Switch·Research·Since 2014

Also known as: benzoate-/vanillate-responsive device, dual-input mammalian gene switch

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

Summary

The benzoate-/vanillate-responsive mammalian gene switch is a dual-input transgene control system engineered for mammalian cells that is induced and repressed by the food additives benzoate and vanillate. It was also reported to function as a modular component in higher-order gene control networks and to regulate a SEAP reporter in implanted designer cells in mice.

Usefulness & Problems

Why this is useful

This system provides small-molecule control of mammalian transgene expression using benzoate and vanillate as antagonistic inputs. It is useful as a modular regulatory element because it was reported to be compatible with other transgene control systems and incorporable 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

It addresses the need for a mammalian gene switch that can integrate two chemical inputs to induce or repress gene expression. The reported design also helps solve the problem of building combinatorial and higher-order mammalian gene control circuits from compatible regulatory modules.

Taxonomy & Function

Primary hierarchy

Mechanism Branch

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

Target processes

recombination

Implementation Constraints

The available evidence indicates use in mammalian gene expression systems and validation with a SEAP reporter in implanted designer cells in mice. However, the supplied material does not describe construct design, delivery method, host cell type, or any required cofactors or expression constraints.

The supplied evidence does not specify the molecular components, promoter architecture, dynamic range, response kinetics, or dose-response characteristics of the switch. Independent replication is not provided in the supplied record, and in vivo evidence is limited to SEAP regulation in implanted designer cells in mice.

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 source4 linked approval claimsfirst-pass slug benzoate-vanillate-responsive-mammalian-gene-switch
we have designed different mammalian gene expression systems that could be induced and repressed by the food additives benzoate and vanillate

Source:

compatibilitysupports

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

Source:

functional responsesupports

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

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:

network dynamicssupports

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

Source:

Comparisons

Source-backed strengths

The device was reported to support both induction and repression of mammalian gene expression in response to benzoate and vanillate. It showed compatibility with other transgene control systems and was assembled into higher-order control networks. In vivo relevance was supported by implanted designer cells in mice, where blood SEAP levels directly correlated with a benzoate-enriched drinking program.

Ranked Citations

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

    Extracted from this source document.