Automated Nucleic Acid Nanostructure Design for Arbitrary Geometries

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Solution Overview

Problem

Current methods for designing DNA assemblies lack a general strategy for structure-based design, particularly for achieving arbitrary wireframe geometries beyond spherical topologies and require semi-automated approaches that result in unstable assemblies, limiting their applications.

Innovation Solution

Developed methods for automated design of nucleic acid nanostructures that generate single-stranded sequences and staple strands to form arbitrary wireframe geometries, enabling the creation of stable, rigid 3D structures without spherical topology constraints, using geometric parameters to define desired shapes and sizes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Extent of automation

If semi-automated design approaches are used for DNA assemblies, then design capability is improved, but assembly stability deteriorates

Engineering Contradiction:

Improvedesign automationVSAvoidassembly stability

Core Design Contradiction:

Extent of automationVSStability of the object's composition

Solution Approach 1:

The patent replaces manual/semi-automated mechanical design processes with a fully automated computational design system that uses algorithms to generate DNA assembly sequences and structures, eliminating the instability caused by manual design limitations and errors

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention changes the design parameters by implementing complete automation with optimized control algorithms, allowing precise adjustment of assembly stability parameters through computational optimization rather than manual estimation

Inventive Principle:

Principle #35Parameter changes

2Device complexity

If spherical topology constraints are applied, then design simplicity is improved, but geometric versatility deteriorates

Engineering Contradiction:

Improvedesign simplicityVSAvoidgeometric versatility

Core Design Contradiction:

Device complexityVSAdaptability or versatility

Solution Approach 1:

The patent implements a universal design system that can handle multiple geometric topologies (spherical, planar, cylindrical, and arbitrary wireframe geometries) through a single automated computational platform, eliminating the need for separate design approaches for different geometries

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention inverts the traditional approach by not constraining designs to spherical topologies but rather allowing the automated system to generate any desired geometry, turning the limitation into a capability for arbitrary shape creation

Inventive Principle:

Principle #13The other way round (Inversion)

3Adaptability or versatility

If arbitrary wireframe geometries are designed, then geometric versatility is improved, but structural stability deteriorates

Engineering Contradiction:

Improvegeometric versatilityVSAvoidstructural stability

Core Design Contradiction:

Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The patent replaces manual structural optimization with automated computational algorithms that calculate and optimize structural stability for arbitrary wireframe geometries, ensuring stability is maintained even as geometric versatility increases

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The invention dynamically adjusts structural parameters through automated optimization, allowing the system to maintain structural stability across diverse geometries by computationally determining optimal parameter values for each specific design

Inventive Principle:

Principle #35Parameter changes

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

Enable the production of structurally stable, rigid nucleic acid nanostructures with arbitrary geometries, allowing for precise control over 3D organization and functionalization, suitable for applications such as delivery, immune stimulation, and sensing.

Implementation Method 1

self-assemble into target shapes using complementary Watson-Crick base pairing

Methodology Applied

Scientific EffectWatson-Crick base pairing: Chemical Bonding

Implementation Method 2

a single-stranded DNA template folds into a three-dimensional (3D) structure corresponding to a desired geometric form

Methodology Applied

Scientific EffectDNA hybridization: Chemical Bonding

Data Source

PatentUS20220383976A1Stable nanoscale nucleic acid assemblies and methods thereof

Publication Date: 2022.12.01 MASSACHUSETTS INST OF TECH

AI summary

Methods for the top-down design of nucleic acid nanostructures of arbitrary geometry based on target shape of spherical or non-spherical topology are described. The methods facilitate 3D molecular programming of lipids, proteins, sugars, and RNAs based on a DNA scaffold of arbitrary 2D or 3D shape. Geometric objects are rendered as node-edge networks of parallel nucleic acid duplexes, and a nucleic acid scaffold routed throughout the network using a spanning tree formula. Nucleic acid nanostructures produced according to top-down design methods are also described. In some embodiments, the nanostructures include single-stranded nucleic acid scaffold, DX crossovers, and staple strands. In other embodiments, the nanostructures include single-stranded nucleic acid scaffold, PX crossovers and no staples. Modified nanostructures include chemically modified nucleotides and conjugated to other molecules are described.