Nucleic Acid Nanostructures for Multispecific Antibody Assembly
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Solution Overview
Problem
The construction of artificial multispecific antibodies is laborious, expensive, and slow due to the need for engineering, producing, and testing each new combination of binding sites, which decelerates early-stage research and requires efficient means for providing bi- or multispecific molecules and targeting multiple cell types.
Innovation Solution
Nucleic acid nanostructures comprising multiple targeting agents and dye molecules, allowing for self-assembly and modular adjustment, are used to create high-valency, multispecific antibody combinations efficiently, leveraging DNA-origami technology for precise geometric orientations and valencies, and enabling bright cell staining and imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If artificial multispecific antibodies are constructed using traditional protein engineering methods, then the desired binding specificity and affinity are achieved, but the process becomes laborious, expensive, and slow
Solution Approach 1:
The patent uses nucleic acid nanostructures as intermediary carriers to present multiple targeting agents (antibodies, antibodies fragments, or other binding molecules) in a controlled spatial arrangement. This mediator approach allows the targeting agents to be delivered and organized without requiring complex protein engineering to create the multispecific molecule itself, thereby accelerating production while maintaining binding specificity
Solution Approach 2:
The patent segments the multispecific functionality into separate targeting agents that are individually produced and then assembled onto a nucleic acid nanostructure platform. This segmentation allows each targeting agent to be optimized and produced independently using existing methods, while the nanostructure provides the multispecific assembly, dramatically reducing the complexity and time of creating artificial multispecific antibodies
2Adaptability or versatility
If multiple targeting agents are combined into a single protein scaffold to create multispecific antibodies, then the desired multivalent binding is achieved, but the device complexity and manufacturing difficulty increase significantly
Solution Approach 1:
The nucleic acid nanostructure serves as an intermediary scaffold that replaces complex protein engineering with simpler nucleic acid assembly. The nanostructure can be programmed to present multiple targeting agents in specific geometries and orientations, achieving multivalent binding without the need to engineer complex multispecific protein molecules
Solution Approach 2:
The patent creates a universal nucleic acid nanostructure platform that can accommodate various types of targeting agents (full antibodies, antibody fragments, other binding molecules) and can be configured for different valencies and spatial arrangements. This universal platform approach allows the same basic structure to be adapted for multiple different multispecific applications, reducing overall complexity
3Adaptability or versatility
If traditional antibody formats are used for targeting, then the binding functionality is sufficient, but the ability to target multiple cell types and achieve high-valency binding is limited
Solution Approach 1:
The patent segments the targeting functionality into multiple separate targeting agents that are presented on the surface of the nucleic acid nanostructure. This segmentation allows each targeting agent to independently bind to different cell types or antigens, achieving high valency and multi-targeting capability that cannot be achieved with traditional single-scaffold antibody formats
Solution Approach 2:
The patent transitions from traditional linear or simple globular antibody structures to three-dimensional nucleic acid nanostructures with controlled geometry and surface area. This dimensional expansion allows for the presentation of multiple targeting agents in specific spatial arrangements, enabling simultaneous targeting of multiple cell types and achieving high-valency binding
Data Source
AI summary
The present invention relates to a nucleic acid nanostructure comprising one or more, preferably at least two, targeting agent(s) and a plurality of dye molecules, preferably at least to dye molecules. The present invention further relates to a composition, preferably pharmaceutical composition, comprising a nucleic acid nanostructure. The present invention also relates to a nanostructure or composition for use in medicine, preferably for use in medical imaging, and for use in a method of preventing, treating, and/or diagnosing a disease. Furthermore, the present invention relates to a method of labelling a target in a sample, to the use of a nanostructure as a stain, and to a kit. Moreover, the present invention further relates to a method of preparing a nanostructure. The present invention further relates to a method of identifying a targeting agent combination having a desired property, a desired effect, and/or a desired spatial organization, and to a method of producing a bi- or multispecific targeting agent-comprising molecule. Furthermore, the present invention relates to a method of screening a sample for a target having at least two target molecules.