α6β4 nAChR Chaperone Co-Expression for Robust Receptor Expression

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing technologies have not been able to express human α6β4 nicotinic acetylcholine receptors robustly in recombinant cell lines, hindering drug discovery efforts targeting these receptors for pain relief.

Innovation Solution

The development of recombinant cells that co-express α6 and β4 subunits of the nicotinic acetylcholine receptor, along with chaperone proteins like BARP, CHAT, and SULT2B1, to enhance expression and facilitate drug discovery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If human α6β4 nicotinic acetylcholine receptors are expressed in recombinant cell lines, then drug discovery for pain relief can be enabled, but the receptors have been refractory to expression and cannot be expressed robustly

Engineering Contradiction:

Improvereceptor expression levelVSAvoidexpression stability

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent introduces chaperone proteins (such as BARP, CHAT, and SULT2B1) as intermediary molecules that facilitate the proper folding, assembly, and surface expression of the α6β4 nAChR complex. These chaperones act as mediators between the receptor subunits and the cellular expression machinery, enabling robust and reliable expression of the previously refractory receptor in HEK293 cells.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If chaperone proteins like BARP, CHAT, and SULT2B1 are co-expressed with α6 and β4 subunits, then receptor expression is enhanced, but the system complexity increases

Engineering Contradiction:

Improvereceptor expression levelVSAvoidexpression system complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent combines multiple expression elements (α6 subunit, β4 subunit, and chaperone proteins like BARP, CHAT, and SULT2B1) into a single integrated expression system in HEK293 cells. By merging these components into one co-expression system, the patent achieves robust receptor expression while managing complexity through systematic design of the expression vectors and transfection protocols.

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS20250277784A1Expression systems for the alpha6beta4 nicotinic acetylcholine receptor and methods of use thereof

Publication Date: 2025.09.04 JANSSEN PHARMA NV

AI summary

Disclosed herein are isolated recombinant cells for the expression of α6β4 nicotinic acetylcholine receptor (nAChR) and methods of use thereof.