Nucleic Acid Mazzocchio for Modular Cargo Encapsulation
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Solution Overview
Problem
Current DNA nanostructures face challenges in encapsulating a wide range of molecules due to their limited size and complexity, leading to restricted cargo delivery and high production costs, which hinders their practical application in therapeutics and diagnostics.
Innovation Solution
The development of nucleic acid nanostructures in the form of a torus-like mazzocchio, composed of subunits connected by linkers, which can encapsulate cargo within a defined three-dimensional cavity, utilizing a simplified assembly process with fewer oligonucleotides, optimizing size for cellular delivery and enhancing stability and biocompatibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If DNA origami approaches are used to create complex nanostructures, then structural complexity and cargo encapsulation capability are improved, but the number of oligonucleotide staples required increases significantly, leading to high production costs and limited practical application
Solution Approach 1:
The patent divides the complex DNA nanostructure into modular repeating units (tiles) that can be assembled from a limited set of oligonucleotide sequences. Each tile is a self-contained module that can be replicated multiple times to form the complete nanostructure, reducing the total number of unique oligonucleotide sequences needed compared to traditional DNA origami approaches.
Solution Approach 2:
The patent designs a universal set of oligonucleotide sequences that can serve multiple functions within the nanostructure. The same sequence types are reused across different tiles and positions, allowing a small library of oligonucleotides to construct complex three-dimensional structures with cargo encapsulation capabilities that would otherwise require hundreds of unique sequences.
2Ease of manufacture
If traditional DNA nanostructures are used, then synthesis is simpler, but size is limited and cargo delivery capability is restricted
Solution Approach 1:
The patent employs a hierarchical assembly approach where smaller DNA tiles are nested within larger repeating units, which in turn form the complete nanostructure. This nested organization allows the system to maintain simple synthesis protocols for individual components while achieving large overall structure sizes and enhanced cargo delivery capability through cumulative assembly.
3Adaptability or versatility
If DNA nanostructures are designed for cargo delivery, then therapeutic and diagnostic applications are enabled, but protection of diverse cargo molecules is limited
Solution Approach 1:
The patent incorporates distinct functional regions within the DNA nanostructure, including protected internal cavities for cargo encapsulation and surface-exposed regions for targeting and delivery functions. This spatial differentiation allows simultaneous optimization of cargo protection in the interior while maintaining delivery capability at the surface, enabling reliable transport of diverse cargo types including proteins, nucleic acids, and small molecules.
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 mazzocchio nanostructures provide cost-effective, stable, and biocompatible delivery of various cargos, including drugs and imaging agents, by encapsulating them within a protected cavity, facilitating efficient intracellular delivery and broadening their applicability in therapeutic, diagnostic, and analytical applications.
Implementation Method 1
DNA nanotechnology uses the fundamental Watson-Crick base pairing principle in double-stranded DNA to fabricate various objects from DNA bricks to DNA origamis
Implementation Method 2
the nanostructures can have one or more three-dimensional cavities of defined size that encapsulate cargo
Data Source
Figure 1A~1B
Figure 1C~1D
Figure 2
AI summary
Provided herein are compositions and methods involving nucleic acid nanostructures that can encapsulate cargo for use in, for example, therapeutic, diagnostic, and analytical applications. The nanostructures can have a plurality of interconnected subunits configured such that the nanostructures have a continuous torus-like structure with a closed three-dimensional cavity. Preferably, the nanostructure is a nucleic acid mazzocchio. The subunits are connected by linkers having defined lengths to constrain the nanostructure into the continuous torus-like shape. The closed three-dimensional cavity is of defined size to encapsulate any cargo of interest. Cargo can also be positioned in the open hole at the center of the nanostructure. The cargo can be a wide range of compounds including, for example, chemical drugs, small molecules, therapeutics, targeting agents, enzymes, dyes, and fluorescent molecules. As such, the disclosed nanostructures are suitable for delivery of one or more therapeutic, toxic, imaging, diagnostic, or prophylactic agents.