Toolkit/translational AND gates

translational AND gates

Construct Pattern·Research·Since 2021

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

Summary

Translational AND gates are artificial mammalian gene circuit elements created by interconnecting Cas-mediated translational switches. They implement combinatorial logic at the level of mRNA translation using Cas proteins that repress or activate transcripts bearing Cas-binding RNA motifs in the 5'-UTR, and a set of 60 such AND gates was reported.

Usefulness & Problems

Why this is useful

These constructs expand synthetic gene circuit design in mammalian cells by enabling combinatorial control at the translational layer. The source states that Cas-mediated translational regulation is compatible with Cas-based transcriptional regulation, which can increase circuit complexity with fewer elements.

Source:

Here we propose CaRTRIDGE (Cas-Responsive Translational Regulation Integratable into Diverse Genomic Engineering) to repurpose CRISPR-associated (Cas) proteins as translational modulators.

Problem solved

They address the problem of building more complex mammalian synthetic circuits without relying only on transcriptional control. Specifically, they provide AND-logic computation through programmable regulation of mRNA translation.

Problem links

Need tighter control over protein production

Derived

Translational AND gates are artificial mammalian gene circuit elements created by interconnecting Cas-mediated translational switches. They implement combinatorial logic at the level of mRNA translation using Cas proteins that repress or activate transcripts bearing Cas-binding RNA motifs in the 5'-UTR, and a set of 60 such AND gates was reported.

Taxonomy & Function

Primary hierarchy

Mechanism Branch

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

Target processes

translation

Implementation Constraints

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

Implementation relies on mRNAs engineered with Cas-binding RNA motifs in the 5'-UTR and expression of the corresponding Cas proteins. The gates were built in a mammalian synthetic circuit context by interconnecting Cas-mediated translational switches, but the provided evidence does not specify construct architectures, delivery methods, or particular Cas orthologs used for the AND gates.

The supplied evidence does not provide quantitative performance metrics such as dynamic range, leak, response time, or cell-type generality for the AND gates. Independent replication and validation outside the cited study are not documented in the provided material.

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Supporting Sources

Ranked Claims

Claim 1circuit constructionsupports2021Source 1needs review

Interconnecting the switches enabled construction of artificial circuits including 60 translational AND gates.

By interconnecting these switches, we designed and built artificial circuits, including 60 translational AND gates.
translational and gates built 60 gates
Claim 2circuit constructionsupports2021Source 1needs review

Interconnecting the switches enabled construction of artificial circuits including 60 translational AND gates.

By interconnecting these switches, we designed and built artificial circuits, including 60 translational AND gates.
translational and gates built 60 gates
Claim 3circuit constructionsupports2021Source 1needs review

Interconnecting the switches enabled construction of artificial circuits including 60 translational AND gates.

By interconnecting these switches, we designed and built artificial circuits, including 60 translational AND gates.
translational and gates built 60 gates
Claim 4circuit constructionsupports2021Source 1needs review

Interconnecting the switches enabled construction of artificial circuits including 60 translational AND gates.

By interconnecting these switches, we designed and built artificial circuits, including 60 translational AND gates.
translational and gates built 60 gates
Claim 5circuit constructionsupports2021Source 1needs review

Interconnecting the switches enabled construction of artificial circuits including 60 translational AND gates.

By interconnecting these switches, we designed and built artificial circuits, including 60 translational AND gates.
translational and gates built 60 gates
Claim 6circuit constructionsupports2021Source 1needs review

Interconnecting the switches enabled construction of artificial circuits including 60 translational AND gates.

By interconnecting these switches, we designed and built artificial circuits, including 60 translational AND gates.
translational and gates built 60 gates
Claim 7circuit constructionsupports2021Source 1needs review

Interconnecting the switches enabled construction of artificial circuits including 60 translational AND gates.

By interconnecting these switches, we designed and built artificial circuits, including 60 translational AND gates.
translational and gates built 60 gates
Claim 8compatibilitysupports2021Source 1needs review

Cas-mediated translational regulation is compatible with transcriptional regulation by Cas proteins and increases synthetic circuit complexity with fewer elements.

Our Cas-mediated translational regulation is compatible with transcriptional regulation by Cas proteins and increases the complexity of synthetic circuits with fewer elements.
Claim 9compatibilitysupports2021Source 1needs review

Cas-mediated translational regulation is compatible with transcriptional regulation by Cas proteins and increases synthetic circuit complexity with fewer elements.

Our Cas-mediated translational regulation is compatible with transcriptional regulation by Cas proteins and increases the complexity of synthetic circuits with fewer elements.
Claim 10compatibilitysupports2021Source 1needs review

Cas-mediated translational regulation is compatible with transcriptional regulation by Cas proteins and increases synthetic circuit complexity with fewer elements.

Our Cas-mediated translational regulation is compatible with transcriptional regulation by Cas proteins and increases the complexity of synthetic circuits with fewer elements.
Claim 11compatibilitysupports2021Source 1needs review

Cas-mediated translational regulation is compatible with transcriptional regulation by Cas proteins and increases synthetic circuit complexity with fewer elements.

Our Cas-mediated translational regulation is compatible with transcriptional regulation by Cas proteins and increases the complexity of synthetic circuits with fewer elements.
Claim 12compatibilitysupports2021Source 1needs review

Cas-mediated translational regulation is compatible with transcriptional regulation by Cas proteins and increases synthetic circuit complexity with fewer elements.

Our Cas-mediated translational regulation is compatible with transcriptional regulation by Cas proteins and increases the complexity of synthetic circuits with fewer elements.
Claim 13compatibilitysupports2021Source 1needs review

Cas-mediated translational regulation is compatible with transcriptional regulation by Cas proteins and increases synthetic circuit complexity with fewer elements.

Our Cas-mediated translational regulation is compatible with transcriptional regulation by Cas proteins and increases the complexity of synthetic circuits with fewer elements.
Claim 14compatibilitysupports2021Source 1needs review

Cas-mediated translational regulation is compatible with transcriptional regulation by Cas proteins and increases synthetic circuit complexity with fewer elements.

Our Cas-mediated translational regulation is compatible with transcriptional regulation by Cas proteins and increases the complexity of synthetic circuits with fewer elements.
Claim 15mechanismsupports2021Source 1needs review

A set of Cas proteins can repress or activate translation of mRNAs containing a Cas-binding RNA motif in the 5'-UTR.

We demonstrate that a set of Cas proteins are able to repress (OFF) or activate (ON) the translation of mRNAs that contain a Cas-binding RNA motif in the 5’-UTR.
Claim 16mechanismsupports2021Source 1needs review

A set of Cas proteins can repress or activate translation of mRNAs containing a Cas-binding RNA motif in the 5'-UTR.

We demonstrate that a set of Cas proteins are able to repress (OFF) or activate (ON) the translation of mRNAs that contain a Cas-binding RNA motif in the 5’-UTR.
Claim 17mechanismsupports2021Source 1needs review

A set of Cas proteins can repress or activate translation of mRNAs containing a Cas-binding RNA motif in the 5'-UTR.

We demonstrate that a set of Cas proteins are able to repress (OFF) or activate (ON) the translation of mRNAs that contain a Cas-binding RNA motif in the 5’-UTR.
Claim 18mechanismsupports2021Source 1needs review

A set of Cas proteins can repress or activate translation of mRNAs containing a Cas-binding RNA motif in the 5'-UTR.

We demonstrate that a set of Cas proteins are able to repress (OFF) or activate (ON) the translation of mRNAs that contain a Cas-binding RNA motif in the 5’-UTR.
Claim 19mechanismsupports2021Source 1needs review

A set of Cas proteins can repress or activate translation of mRNAs containing a Cas-binding RNA motif in the 5'-UTR.

We demonstrate that a set of Cas proteins are able to repress (OFF) or activate (ON) the translation of mRNAs that contain a Cas-binding RNA motif in the 5’-UTR.
Claim 20mechanismsupports2021Source 1needs review

A set of Cas proteins can repress or activate translation of mRNAs containing a Cas-binding RNA motif in the 5'-UTR.

We demonstrate that a set of Cas proteins are able to repress (OFF) or activate (ON) the translation of mRNAs that contain a Cas-binding RNA motif in the 5’-UTR.
Claim 21mechanismsupports2021Source 1needs review

A set of Cas proteins can repress or activate translation of mRNAs containing a Cas-binding RNA motif in the 5'-UTR.

We demonstrate that a set of Cas proteins are able to repress (OFF) or activate (ON) the translation of mRNAs that contain a Cas-binding RNA motif in the 5’-UTR.
Claim 22repurposing scopesupports2021Source 1needs review

Various CRISPR-related technologies, including anti-CRISPR and split-Cas9 platforms, can be repurposed to control translation.

Moreover, we show that various CRISPR-related technologies, including anti-CRISPR and split-Cas9 platforms, can be repurposed to control translation.
Claim 23repurposing scopesupports2021Source 1needs review

Various CRISPR-related technologies, including anti-CRISPR and split-Cas9 platforms, can be repurposed to control translation.

Moreover, we show that various CRISPR-related technologies, including anti-CRISPR and split-Cas9 platforms, can be repurposed to control translation.
Claim 24repurposing scopesupports2021Source 1needs review

Various CRISPR-related technologies, including anti-CRISPR and split-Cas9 platforms, can be repurposed to control translation.

Moreover, we show that various CRISPR-related technologies, including anti-CRISPR and split-Cas9 platforms, can be repurposed to control translation.
Claim 25repurposing scopesupports2021Source 1needs review

Various CRISPR-related technologies, including anti-CRISPR and split-Cas9 platforms, can be repurposed to control translation.

Moreover, we show that various CRISPR-related technologies, including anti-CRISPR and split-Cas9 platforms, can be repurposed to control translation.
Claim 26repurposing scopesupports2021Source 1needs review

Various CRISPR-related technologies, including anti-CRISPR and split-Cas9 platforms, can be repurposed to control translation.

Moreover, we show that various CRISPR-related technologies, including anti-CRISPR and split-Cas9 platforms, can be repurposed to control translation.
Claim 27repurposing scopesupports2021Source 1needs review

Various CRISPR-related technologies, including anti-CRISPR and split-Cas9 platforms, can be repurposed to control translation.

Moreover, we show that various CRISPR-related technologies, including anti-CRISPR and split-Cas9 platforms, can be repurposed to control translation.
Claim 28repurposing scopesupports2021Source 1needs review

Various CRISPR-related technologies, including anti-CRISPR and split-Cas9 platforms, can be repurposed to control translation.

Moreover, we show that various CRISPR-related technologies, including anti-CRISPR and split-Cas9 platforms, can be repurposed to control translation.
Claim 29tool proposalsupports2021Source 1needs review

CaRTRIDGE repurposes CRISPR-associated proteins as translational modulators.

Here we propose CaRTRIDGE (Cas-Responsive Translational Regulation Integratable into Diverse Genomic Engineering) to repurpose CRISPR-associated (Cas) proteins as translational modulators.
Claim 30tool proposalsupports2021Source 1needs review

CaRTRIDGE repurposes CRISPR-associated proteins as translational modulators.

Here we propose CaRTRIDGE (Cas-Responsive Translational Regulation Integratable into Diverse Genomic Engineering) to repurpose CRISPR-associated (Cas) proteins as translational modulators.
Claim 31tool proposalsupports2021Source 1needs review

CaRTRIDGE repurposes CRISPR-associated proteins as translational modulators.

Here we propose CaRTRIDGE (Cas-Responsive Translational Regulation Integratable into Diverse Genomic Engineering) to repurpose CRISPR-associated (Cas) proteins as translational modulators.
Claim 32tool proposalsupports2021Source 1needs review

CaRTRIDGE repurposes CRISPR-associated proteins as translational modulators.

Here we propose CaRTRIDGE (Cas-Responsive Translational Regulation Integratable into Diverse Genomic Engineering) to repurpose CRISPR-associated (Cas) proteins as translational modulators.
Claim 33tool proposalsupports2021Source 1needs review

CaRTRIDGE repurposes CRISPR-associated proteins as translational modulators.

Here we propose CaRTRIDGE (Cas-Responsive Translational Regulation Integratable into Diverse Genomic Engineering) to repurpose CRISPR-associated (Cas) proteins as translational modulators.
Claim 34tool proposalsupports2021Source 1needs review

CaRTRIDGE repurposes CRISPR-associated proteins as translational modulators.

Here we propose CaRTRIDGE (Cas-Responsive Translational Regulation Integratable into Diverse Genomic Engineering) to repurpose CRISPR-associated (Cas) proteins as translational modulators.
Claim 35tool proposalsupports2021Source 1needs review

CaRTRIDGE repurposes CRISPR-associated proteins as translational modulators.

Here we propose CaRTRIDGE (Cas-Responsive Translational Regulation Integratable into Diverse Genomic Engineering) to repurpose CRISPR-associated (Cas) proteins as translational modulators.

Approval Evidence

1 source1 linked approval claimfirst-pass slug translational-and-gates
By interconnecting these switches, we designed and built artificial circuits, including 60 translational AND gates.

Source:

circuit constructionsupports

Interconnecting the switches enabled construction of artificial circuits including 60 translational AND gates.

By interconnecting these switches, we designed and built artificial circuits, including 60 translational AND gates.

Source:

Comparisons

Source-backed strengths

The reported system supported construction of 60 translational AND gates, indicating substantial circuit-building capacity. The underlying switches can either repress or activate translation from mRNAs containing a Cas-binding motif in the 5'-UTR, providing flexible regulatory behavior.

Compared with 4pLRE-cPAOX1

translational AND gates and 4pLRE-cPAOX1 address a similar problem space because they share translation.

Shared frame: same top-level item type; shared target processes: translation; shared mechanisms: translation_control

Strengths here: looks easier to implement in practice.

translational AND gates and blue-light-activated DNA template ON switch address a similar problem space because they share translation.

Shared frame: same top-level item type; shared target processes: translation; shared mechanisms: translation_control

Strengths here: looks easier to implement in practice.

translational AND gates and functional electrical stimulation address a similar problem space because they share translation.

Shared frame: same top-level item type; shared target processes: translation; shared mechanisms: translation_control

Ranked Citations

  1. 1.

    Extracted from this source document.