Toolkit/switchable inteins

switchable inteins

Multi-Component Switch·Research·Since 2018

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

Summary

Switchable inteins are conditional protein-splicing systems in which intein activity is regulated post-translationally to control the state of pre-existing proteins. The cited review specifically discusses strategies for controlling intein activity, with emphasis on approaches intended for use in living cells.

Usefulness & Problems

Why this is useful

These systems are useful because post-translational control of pre-existing proteins can provide faster responses than regulation at the level of gene expression. The available evidence supports their value as a framework for conditional control of protein function in cellular contexts, but does not provide specific application benchmarks.

Source:

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.

Problem solved

Switchable inteins address the problem of how to regulate protein state after translation rather than by controlling synthesis of the encoded protein. The cited evidence supports this as a strategy for achieving faster functional responses, particularly for live-cell-compatible protein control.

Source:

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.

Problem links

Need inducible protein relocalization or recruitment

Derived

Switchable inteins are conditional protein-splicing systems in which intein activity is controlled post-translationally to regulate the state of pre-existing proteins. The cited review focuses on strategies for controlling intein activity, particularly approaches intended to be compatible with applications in living cells.

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

localization

Implementation Constraints

cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: multi component delivery burdenoperating role: actuatoroperating role: regulatorswitch architecture: multi component

The available evidence only states that the reviewed control strategies focus on compatibility with applications in living cells. No specific construct architectures, cofactors, delivery methods, expression systems, or trigger modalities are described in the supplied material.

The supplied evidence is limited to high-level review statements and does not identify specific intein systems, triggers, host organisms, or quantitative performance metrics. It also does not document independent experimental validation, dynamic range, background splicing, or localization-specific case studies.

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Supporting Sources

Ranked Claims

Claim 1comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 2comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 3comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 4comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 5comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 6comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 7comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 8comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 9comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 10comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 11comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 12comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 13comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 14comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 15comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 16comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 17comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 18comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 19comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 20comparative advantagesupports2018Source 1needs review

Post-translational modification of pre-existing proteins can provide faster responses than controlling proteins by regulating expression of their encoding genes.

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.
Claim 21review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 22review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 23review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 24review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 25review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 26review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 27review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 28review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 29review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 30review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 31review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 32review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 33review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 34review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 35review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 36review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 37review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 38review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 39review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 40review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 41review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 42review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 43review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 44review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 45review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 46review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 47review scope statementneutral2018Source 1needs review

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.
Claim 48use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 49use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 50use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 51use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 52use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 53use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 54use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 55use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 56use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 57use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 58use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 59use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 60use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 61use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 62use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 63use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 64use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 65use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 66use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 67use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 68use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 69use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 70use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 71use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 72use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 73use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.
Claim 74use casesupports2018Source 1needs review

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.

Approval Evidence

1 source2 linked approval claimsfirst-pass slug switchable-inteins
Switchable inteins for conditional protein splicing

Source:

review scope statementneutral

The review discusses methods to control intein activity with a focus on approaches compatible with applications in living cells.

Here we discuss methods to control intein activity with a focus on those compatible with applications in living cells.

Source:

use casesupports

Conditional splicing mediated by inteins is presented as an attractive method for controlling protein function or localization.

Conditional splicing of internal protein domains, termed inteins, is an attractive methodology for this purpose.

Source:

Comparisons

Source-backed strengths

A key stated advantage is the potential for faster response kinetics relative to gene-expression-based control, because modulation occurs on pre-existing proteins. The review also indicates that methods have been developed with compatibility for applications in living cells as an explicit design consideration.

Source:

Proteins can be controlled in several ways, for instance by regulating the expression of their encoding genes with small molecules or light. However, post-translationally modifying pre-existing proteins to regulate their function or localization leads to faster responses.

Compared with CLASP

switchable inteins and CLASP address a similar problem space because they share localization.

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

Strengths here: looks easier to implement in practice.

Compared with iLID/SspB

switchable inteins and iLID/SspB address a similar problem space because they share localization.

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

Relative tradeoffs: appears more independently replicated.

Compared with synthetic condensates

switchable inteins and synthetic condensates address a similar problem space because they share localization.

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

Ranked Citations

  1. 1.
    StructuralSource 1Biological Chemistry2018Claim 20Claim 20Claim 20

    Seeded from load plan for claim cl2. Extracted from this source document.