Toolkit/tandem-dimer nano (tdnano)

tandem-dimer nano (tdnano)

Multi-Component Switch·Research·Since 2019

Also known as: tdnano

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

Summary

tdnano is a constructed tandem-dimer of the iLID binding partner nano used as the second component of a blue-light-responsive iLID system. In the reported opto-receptor tyrosine kinase designs, blue light drives recruitment of two iLID-fused RTK molecules to tdnano, enabling receptor dimerization and activation.

Usefulness & Problems

Why this is useful

tdnano provides a modular way to convert the iLID light-induced interaction into enforced pairing of two receptor tyrosine kinase molecules. In the reported opto-iTrkA and opto-iTrkB systems, this enabled light-dependent activation of downstream ERK and Akt signaling and supported multi-day, population-level TrkA activation in PC12 cells.

Problem solved

A central challenge for optogenetic control of RTKs is achieving light-dependent receptor dimerization in a defined multi-component format. tdnano addresses this by presenting a tandem nano scaffold that recruits two copies of iLID-RTK under blue light, thereby coupling iLID binding to RTK activation.

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

signaling

Input: Light

Implementation Constraints

tdnano is implemented as a constructed tandem-dimer of nano and functions as the binding partner component for iLID-based blue-light control. The reported use case requires co-expression with iLID-fused RTK constructs, where blue light induces recruitment of two iLID-RTK molecules to tdnano.

The available evidence is limited to a single 2019 study and specifically to opto-iTrkA and opto-iTrkB implementations. Quantitative performance characteristics, broader receptor compatibility, and independent replication are not provided in the supplied evidence.

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Supporting Sources

Ranked Claims

Claim 1activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 2activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 3activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 4activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 5activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 6activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 7activitysupports2019Source 1needs review

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.
Claim 8compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 9compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 10compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 11compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 12compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 13compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 14compatibilitysupports2019Source 1needs review

opto-iTrkA is compatible with multi-day and population-level activation of TrkA in PC12 cells.

We further show with our opto-iTrkA that the system is compatible with multi-day and population-level activation of TrkA in PC12 cells.
Claim 15mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 16mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 17mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 18mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 19mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 20mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 21mechanismsupports2019Source 1needs review

In the absence of light, iLID-RTK is cytosolic, monomeric, and inactive.

In the absence of light, the iLID-RTK is cytosolic, monomeric and inactive.
Claim 22mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 23mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 24mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 25mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 26mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 27mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 28mechanismsupports2019Source 1needs review

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.
Claim 29targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination
Claim 30targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination
Claim 31targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination
Claim 32targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination
Claim 33targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination
Claim 34targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination
Claim 35targetingsupports2019Source 1needs review

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination

Approval Evidence

1 source3 linked approval claimsfirst-pass slug tandem-dimer-nano-tdnano
with a constructed tandem-dimer of its binding partner nano (tdnano)

Source:

activitysupports

opto-iTrkA and opto-iTrkB reproduce downstream ERK and Akt signaling only in the presence of tdnano.

We demonstrate that iLID opto-iTrkA and opto-iTrkB are capable of reproducing downstream ERK and Akt signaling only in the presence of tdnano.

Source:

mechanismsupports

Under blue light, the iLID plus tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Under blue light, the iLID + tdnano system recruits two copies of iLID-RTK to tdnano, dimerizing and activating the RTK.

Source:

targetingsupports

Genetic targeting of tdnano enables RTK activation at a specific subcellular location even with whole-cell illumination.

By leveraging genetic targeting of tdnano, we achieve RTK activation at a specific subcellular location even with whole-cell illumination

Source:

Comparisons

Source-backed strengths

The reported system reproduced downstream ERK and Akt signaling for opto-iTrkA and opto-iTrkB only in the presence of tdnano, supporting its functional necessity in these designs. It was also reported to be compatible with multi-day and population-level activation of TrkA in PC12 cells.

Ranked Citations

  1. 1.

    Extracted from this source document.