DNA Origami Nanostructures for Stoichiometric Multi-Gene Expression
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Solution Overview
Problem
Existing technologies face challenges in efficiently delivering and expressing multiple genes, particularly in vivo, with limited development for DNA origami in gene therapy, and a need for tools that can encode and express two or more genes in controlled stoichiometric ratios.
Innovation Solution
Nucleic acid nanostructures, such as DNA origami, are designed with scaffold strands and staple strands to encode genes, incorporating enhancer staple strands, loop structures, and nuclear targeting sequences for enhanced gene expression, allowing simultaneous delivery and expression of multiple genes in controlled ratios.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If multiple genes are delivered using conventional methods, then gene delivery can be achieved, but precise control of stoichiometric ratios and simultaneous expression remains challenging
Solution Approach 1:
The patent combines multiple gene-coding nucleic acid sequences into a single DNA origami nanostructure, integrating multiple genetic payloads into one unified delivery vehicle. This merging approach enables simultaneous delivery of multiple genes with precise stoichiometric control while simplifying the delivery system compared to separate conventional delivery methods
Solution Approach 2:
The DNA origami nanostructure serves multiple functions: it acts as a delivery vehicle, a structural scaffold for organizing multiple genes, and a control mechanism for stoichiometric ratios. This multi-functionality resolves the contradiction by enabling precise ratio control without proportionally increasing system complexity
2Adaptability or versatility
If DNA origami is used for gene therapy applications, then structural programmability and biocompatibility are improved, but limited development for in vivo gene expression remains
Solution Approach 1:
The patent incorporates specific functional elements at localized positions within the DNA origami structure, including enhancer staple strands at particular locations, loop structures at specific sites, and nuclear targeting sequences positioned to facilitate nuclear import. This local optimization of specific regions enhances in vivo expression efficiency while preserving the overall structural programmability
Solution Approach 2:
The nanostructure is pre-assembled with all necessary components including genes, enhancers, and targeting sequences before delivery. The DNA origami structure is constructed in advance with predetermined stoichiometric ratios and spatial arrangements, enabling reliable in vivo expression without requiring complex in vivo assembly processes
3Productivity
If genes are packaged into compact DNA origami structures, then delivery efficiency is improved, but expression of multiple genes in controlled ratios becomes more difficult
Solution Approach 1:
The patent segments the DNA origami structure into distinct functional modules, with each gene-coding nucleic acid sequence positioned in specific locations along the scaffold strand. The structure is divided into repeat units or modular sections that can each contain one or more genes, allowing independent optimization of each segment while maintaining overall compactness and delivery efficiency
Solution Approach 2:
Multiple gene-coding sequences are nested within the DNA origami scaffold structure, with each gene positioned in a defined location along the nanostructure. This nesting arrangement maintains compact size for efficient delivery while enabling precise control of the number and ratio of different genes through the design of the scaffold sequence
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 nanostructures enable highly efficient and robust gene expression, with improved transfection efficiency and controlled stoichiometry, suitable for in vitro, ex vivo, and in vivo applications, particularly for mammalian genes.
Implementation Method 1
wherein said nanostructure, preferably said at least one scaffold strand, comprises at least one nucleic acid sequence encoding a gene
Implementation Method 2
comprising at least one scaffold strand and a plurality of staple strands
Data Source
AI summary
The present invention relates to a nucleic acid nanostructure comprising at least one scaffold strand and a plurality of staple strands, wherein said nanostructure, preferably said at least one scaffold strand, comprises at least one nucleic acid sequence encoding a gene. The present invention further relates to a composition comprising a nucleic acid nanostructure, and to a collection of nucleic acid sequences or collection of plasmids encoding a nucleic acid nanostructure. Furthermore, the present invention relates to a nucleic acid nanostructure or composition comprising a nucleic acid nanostructure for use in medicine; preferably for use in a method of preventing, treating and/or diagnosing a disease or disorder. The present invention also relates to a method of expressing a gene from a nucleic acid nanostructure, and to a use of a nanostructure or of a composition for gene expression.