Biomolecular Self-Assembly via Hairpin Monomer Hybridization

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Solution Overview

Problem

Current protocols for self-assembling synthetic DNA nanostructures rely on annealing procedures and lack control over transient system dynamics, limiting the ability to engineer molecules that assemble into prescribed target structures without kinetic traps and environmental responsiveness.

Innovation Solution

The development of hairpin monomers with specific nucleic acid sequences that self-assemble into prescribed three-dimensional structures through programmed complementarity relationships, allowing for dynamic functions and environmental responsiveness under isothermal conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If annealing procedures are used for self-assembling synthetic DNA nanostructures, then the structures can form through thermal cycling, but control over transient system dynamics is lost and kinetic traps cannot be avoided

Engineering Contradiction:
Improvecontrol over transient system dynamicsVSAvoidassembly procedure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by transitioning from thermal cycling (annealing) to isothermal conditions, and from spontaneous assembly to catalyst-controlled assembly. This allows precise control over transient dynamics and assembly kinetics while maintaining reliability of structure formation.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces catalysts as intermediary molecules that mediate the self-assembly process. These catalysts control the kinetics of formation and help avoid kinetic traps, providing the missing control over transient system dynamics without requiring complex procedural interventions.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Manufacturing precision

If spontaneous self-assembly is used, then the process is simple and requires no external control, but the ability to engineer molecules that assemble into prescribed target structures without kinetic traps is limited

Engineering Contradiction:
Improveprecision of target structure assemblyVSAvoidease of self-assembly process
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

Catalysts serve as intermediaries that guide the self-assembly process toward prescribed target structures. They provide the necessary control to avoid kinetic traps and ensure high manufacturing precision while maintaining the simplicity of a one-pot assembly process.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces thermal mechanical control (annealing cycles) with chemical catalytic control. This substitution enables precise engineering of assembly pathways and target structures while maintaining ease of manufacture through isothermal conditions.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Adaptability or versatility

If isothermal conditions are used with catalysts, then dynamic functions and environmental responsiveness are enabled, but the assembly protocol becomes more complex than simple annealing

Engineering Contradiction:
Improveenvironmental responsivenessVSAvoidassembly protocol complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

Catalysts act as intermediaries that enable environmental responsiveness and dynamic functions under isothermal conditions. They provide the mechanistic basis for adaptability while the isothermal protocol itself remains relatively simple, requiring only temperature maintenance rather than cyclic heating and cooling.

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

Enables the assembly of complex molecular structures with kinetic control, avoiding kinetic traps and permitting environmental responsiveness, facilitating dynamic functions such as bio-markers and smart therapeutics.

Implementation Method 1

hairpin monomers with specific nucleic acid sequences that self-assemble into prescribed three-dimensional structures through programmed complementarity relationships

Methodology Applied
Scientific EffectHybridization: Chemical Bonding

Implementation Method 2

upon binding of the first hairpin monomer to an initiator molecule, the first monomer, the second monomer, and the third monomer self-assemble

Methodology Applied
Scientific EffectHybridization: Chemical Bonding

Data Source

PatentUS9834439B2Biomolecular self-assembly
Publication Date: 2017.12.05 CALIFORNIA INST OF TECH
  • US9834439B2 patent drawing
  • US9834439B2 patent drawing
  • US9834439B2 patent drawing

AI summary

The present invention relates generally to programming of biomolecular self-assembly pathways and related methods and constructs for self-assembly of prescribed two and three-dimensional structures.