Single-Stranded Nucleic Acid Knots With High-Crossing 3D Folding
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Solution Overview
Problem
Existing technologies face challenges in designing and constructing highly knotted nanostructures with well-defined geometries and high folding efficiency using single-stranded nucleic acids (ssNAs) for molecular assembly.
Innovation Solution
The development of knotted, self-assembled single-stranded nucleic acid (ssNA) nanostructures with specific crossing numbers and paranemic cohesion crossovers, which self-assemble into 3-dimensional shapes with high folding efficiencies exceeding 50%, 85%, or even 90% and above, and can include therapeutic or diagnostic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Shape
If traditional DNA knotting methods are used, then molecular knots can be formed, but the geometric complexity and control over assembly behavior are insufficient
Solution Approach 1:
The single-stranded nucleic acid is divided into multiple domains with specific secondary structures (hairpins, loops, stems) that can independently form and then assemble. Each domain acts as a modular unit with defined geometry, allowing complex knotted structures to be constructed from simpler segments through hierarchical self-assembly.
Solution Approach 2:
The patent implements hierarchical folding where smaller secondary structures (such as hairpins and loops) are nested within larger tertiary structures. The single-stranded nucleic acid folds into compact domains that contain internal structures, creating a nested organization that enables precise geometric control at multiple scales simultaneously.
2Shape
If highly knotted nanostructures with high crossing numbers are constructed, then geometric complexity increases, but folding efficiency decreases
Solution Approach 1:
The nucleic acid sequence is pre-designed with predetermined secondary structure domains arranged in specific sequences. These domains are programmed to form in a specific hierarchical order during self-assembly, with smaller structures forming first and guiding the subsequent formation of larger structures. This preliminary organization of the sequence enables high crossing number knots to form efficiently without random trial-and-error.
Solution Approach 2:
The patent optimizes specific parameters including the length and sequence composition of hairpin loops, stem regions, and crossover points. By adjusting these parameters, the folding kinetics are controlled to favor the formation of highly knotted structures. The GC content, loop sizes, and stem lengths are tuned to ensure that even complex knots with many crossings can assemble with high efficiency.
3Adaptability or versatility
If single-stranded nucleic acids are used for self-assembly, then programmability is achieved, but control over folding pathways and intermediates is limited
Solution Approach 1:
Different regions of the single-stranded nucleic acid are assigned different local properties: some regions contain strong hairpin formations with high GC content, others have flexible loop sequences, and specific positions include crossover domains. This local differentiation enables each domain to fold independently with defined characteristics, while the collective assembly follows a predictable pathway determined by the local properties of each segment.
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 solution enables the creation of nanostructures with precise geometries and high folding efficiencies, allowing for applications in immune response induction and therapeutic treatments, such as cancer treatment, by leveraging the programmability of nucleic acids for controlled molecular assembly.
Implementation Method 1
comprising at least one paranemic cohesion crossover
Implementation Method 2
self-assembled single-stranded nucleic acid (ssNA) nanostructure
Data Source
AI summary
In some embodiments, complex molecular knots with high crossing numbers are achieved by folding, following a prescribed folding order, single-stranded DNA or RNA of customized sequences into target shapes. Such complex molecular knots with high crossing numbers are useful for biomedical applications including use as immunostimulatory agents and/or protein hosts and carriers.