Nucleic Acid Origami Tile Self-Replication via Thermal Cycling

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Solution Overview

Problem

Current artificial systems lack the ability to self-replicate and evolve in a controlled manner, limiting their potential for applications in nanotechnology and materials science, where self-replication and selective pressure-driven evolution are key phenomena.

Innovation Solution

A method for the exponential amplification and selective replication of nucleic acid origami tiles, where seeds of monomeric units are used to form multimers through complementary pairing and photo-crosslinking, allowing for the preferential replication of designated multimers with specific properties under environmental changes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If artificial systems are designed to self-replicate and evolve, then the system complexity and control mechanisms increase significantly

Engineering Contradiction:
Improveself-replication capabilityVSAvoidsystem complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The system is divided into discrete monomeric nucleic acid origami tiles that self-assemble into multimeric structures. Each monomer contains specific functional domains (binding sites, crosslinking sites) that enable modular self-assembly and replication without requiring complex centralized control mechanisms.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The nucleic acid origami tiles utilize intrinsic properties of nucleic acids (complementary base pairing, hybridization) to automatically perform recognition, binding, and assembly functions. The system self-regulates through thermodynamic principles and molecular recognition without external intervention, enabling self-replication while minimizing control complexity.

Inventive Principle:
Principle #25Self-service

2Manufacturing precision

If selective exponential amplification of designated multimers is achieved, then the manufacturing precision and selectivity improve, but the process complexity increases

Engineering Contradiction:
Improveselectivity of amplificationVSAvoidprocess complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

Different monomeric tiles are designed with distinct local properties (complementary sticky ends, specific crosslinking sites, unique sequences) that enable selective recognition and binding. This local differentiation allows the system to distinguish between different multimer types and selectively amplify designated structures without requiring complex global control mechanisms.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The system exploits changes in environmental parameters (temperature, pH, ionic strength) to control the stability and specificity of nucleic acid hybridization. By adjusting these parameters, the system can selectively stabilize desired multimer formations while destabilizing non-specific interactions, achieving high selectivity through physical-chemical parameter optimization rather than complex process control.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If exponential amplification is performed through multiple replication cycles, then the productivity increases, but the time required for the process increases

Engineering Contradiction:
Improveamplification rateVSAvoidreplication cycle time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The replication process is designed to proceed continuously through multiple cycles without interruption. Monomeric tiles remain in solution and can immediately participate in subsequent replication events after each cycle, maintaining continuous productive action. The system avoids downtime between cycles by using in-situ reagents and maintaining optimal conditions throughout the amplification process.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The replication process utilizes periodic temperature cycling (thermal denaturation and annealing) to drive each replication cycle. This periodic action efficiently separates newly formed multimers from templates while maintaining high concentrations of reactive monomers, enabling rapid successive cycles. The periodic thermal protocol optimizes both speed and fidelity of each cycle, maximizing overall productivity.

Inventive Principle:
Principle #19Periodic action

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

This approach enables the exponential growth of specific nucleic acid origami tiles, demonstrating a 7 million-fold amplification in 24 cycles, and allows for the selective evolution of multimers with desired properties by controlling environmental stimuli, such as light exposure.

Implementation Method 1

forming a multimer from monomers of seed nucleic acid origami tiles by cohesion of complementary horizontal sticky cohesive ends between edges of adjacent monomers

Methodology Applied
Scientific EffectComplementary base pairing: Chemical Bonding

Implementation Method 2

covalently linking the 1G tiles in sticky end cohesion with each other in the stacked multimer

Methodology Applied
Scientific EffectPhoto-crosslinking: Photopolymerisation

Implementation Method 3

heating to denature the horizontal sticky end cohesion between monomers of seed tiles and the vertical sticky end cohesion between monomers of seed tiles and 1G tiles to separate the heat resistant covalently linked 1G tiles as a multimer of 1G tiles

Methodology Applied
Scientific EffectThermal denaturation: Melting

Implementation Method 4

allowing the monomers to anneal to each other by horizontal sticky end cohesion between edges of adjacent 1G monomeric tiles and to the multimer of seed tiles by sticky end cohesion between sticky cohesive ends protruding from the faces of adjacent seed and 1G tiles to form a stacked multimer of seed and 1G tiles

Methodology Applied
Scientific EffectAnnealing: Annealing

Data Source

PatentUS10513535B2Self-replication of nucleic acid origami tiles
Publication Date: 2019.12.24 NEW YORK UNIV
  • US10513535B2 patent drawing
  • US10513535B2 patent drawing
  • US10513535B2 patent drawing

AI summary

The present invention provides a method for self-replication of multimers of nucleic acid origami tiles by exponentially amplifying the multimer from initial seeds of monomeric units of nucleic acid origami tiles and also provides for the selective exponential amplification of a designated multimer, such as with specific properties or characteristics, over one or more competing multimers in the presence of a mixture of monomers for each of the possible multimers. The selection of the designated multimer based on an environmental change allows the designated multimer to outgrow all competing multimers.