Triggered DNA Nanopore Assembly for Membrane Leak Reduction

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Solution Overview

Problem

Conventional membrane-spanning nanopores are typically constitutively open, limiting their functional complexity and leading to leakiness, which reduces their application potential in analyte sensing and drug delivery.

Innovation Solution

The development of DNA nanotechnology to construct a functionally advanced membrane pore that assembles from a plurality of membrane surface-associated subunits following a defined triggered activation, integrating molecular recognition, repositioning, and assembly into a functional membrane-spanning channel.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If conventional membrane-spanning nanopores are designed to be constitutively open, then ease of operation is improved, but reliability deteriorates due to leakiness and background noise

Engineering Contradiction:
Improveease of operationVSAvoidreliability
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The nanopore is designed with dynamic control capability, transitioning from a static constitutively open state to a dynamically controllable state. The pore can switch between closed and open states in response to external stimuli (light, chemical triggers), allowing it to adapt its functionality rather than remaining permanently open. This dynamic behavior resolves the contradiction by enabling reliable closed states while maintaining operational control.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The invention changes the operational parameters of the nanopore by introducing stimuli-responsive elements that alter the pore's conformational state. By using photo-switchable molecules or chemically responsive polymers, the pore's opening state can be controlled through parameter changes (light wavelength, chemical concentration), transforming it from a fixed open structure to a controllable system that can reliably close when needed.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If membrane-spanning nanopores are designed to be constitutively open, then ease of manufacture is improved, but object-generated harmful factors worsen due to cargo leakage and background noise

Engineering Contradiction:
Improveease of manufactureVSAvoidobject-generated harmful factors
Core Design Contradiction:
Ease of manufactureVSObject-generated harmful factors

Solution Approach 1:

The nanopore is pre-configured with closed or partially closed conformation during manufacture, and the opening action is triggered only when needed. This preliminary closed state prevents cargo leakage and background noise during insertion and storage, while the triggering mechanism (light, chemical) enables opening only during active use, thereby eliminating harmful effects without complicating the manufacturing process.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention introduces intermediary molecules (photo-switchable compounds, chemically responsive polymers) that mediate between the simple structural nanopore and the desired controlled opening function. These intermediaries allow the pore to remain structurally simple and easy to manufacture while adding the capability to close reliably, preventing cargo leakage and background noise through the intermediary's conformational changes.

Inventive Principle:
Principle #24Intermediary (Mediator)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The controlled assembly of the nanopore achieves a fully closed state, reducing leakiness and enhancing the pores' application potential in sensing and drug delivery by providing a controlled turn-on signal and preventing background noise.

Implementation Method 1

DNA nanostructures have a highly controllable architecture which is based on predictable folding using base-pairing rules

Methodology Applied
Scientific EffectBase-pairing: Chemical Bonding

Implementation Method 2

at least one hydrophobic anchor; and wherein the component modules are able to associate and interact with a surface of a semifluid membrane via the anchor

Methodology Applied
Scientific EffectHydrophobic interaction: Hydrophobe

Implementation Method 3

a plurality of single stranded nucleic acid lock sequences that are capable of hybridising with the single stranded sequence of the assembly interface

Methodology Applied
Scientific EffectNucleic acid hybridization: Chemical Bonding

Data Source

PatentUS20250052737A1Trigger-assembled membrane-spanning nucleic acid nanostructures
Publication Date: 2025.02.13 UCL BUSINESS LTD
  • US20250052737A1 patent drawing
  • US20250052737A1 patent drawing
  • US20250052737A1 patent drawing

AI summary

A nucleic acid nanostructure is provided that comprises a plurality of component modules, each component module comprising a nucleic acid sequence and at least one membrane anchor. The plurality of component modules are capable of undertaking a controlled assembly in response to an external stimulus to form the nanostructure and also to penetrate a semifluid membrane upon or following the controlled assembly. Methods of assembling the nanostructure as well as uses in sensors, drug delivery and release of imaging substances are also provided.