Nucleic Acid Scaffolded Artificial Immune Complexes for Antigen Spacing
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Solution Overview
Problem
Current methods for synthesizing immune complexes lack precise control over their structure and composition, leading to heterogeneous aggregates and difficulty in packaging payloads for cell delivery, and are unable to prescribe antigen valency and spacing for controlling the overall shape and structure of assembled ICs.
Innovation Solution
The development of nucleic acid scaffolded artificial immune complexes (ICs) with addressable sites and epitopes patterned in three dimensions to recruit antibodies, allowing for precise control over IC structure and composition, including the use of nucleic acid foldings with functional groups and single-stranded NA handles for hybridization, and geometric groupings to regulate antibody binding and composition.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If complexation method is used to synthesize immune complexes, then the synthesis process is simple, but the structure and composition control is poor leading to heterogeneous aggregates
Solution Approach 1:
The patent introduces a nucleic acid scaffold as an intermediary structure that mediates the assembly of immune complexes. The scaffold provides a predefined geometric framework with multiple binding sites that precisely control the positioning and spacing of antigens and antibodies, transforming the uncontrolled complexation process into a structured assembly process while maintaining relative simplicity.
Solution Approach 2:
The immune complex is segmented into distinct functional modules: a nucleic acid scaffold component, antigen components, and antibody components. Each module can be independently designed and synthesized, then assembled together through specific binding interactions. This segmentation enables precise control over the overall structure and composition while simplifying the manufacturing process through modular assembly.
2Manufacturing precision
If recombinant expression method is used to synthesize immune complexes, then the composition is controlled, but the ability to package payloads within IC is lost
Solution Approach 1:
The nucleic acid scaffold serves multiple functions simultaneously: it provides structural organization for antigen-antibody assembly, enables precise composition control through designed binding sites, and offers payload packaging capability through its inherent nucleic acid structure that can encapsulate or conjugate therapeutic agents. This multi-functionality resolves the trade-off between composition control and payload packaging versatility.
3Manufacturing precision
If antigens are arrayed on nano- and micro-particles to assemble ICs, then the IC structure is controlled, but the antigen valency and spacing prescription is difficult
Solution Approach 1:
The nucleic acid scaffold implements local quality by providing different types of binding sites at different locations on the scaffold structure. Specific regions of the scaffold are designed with particular spacing and orientation of binding sites to control antigen valency and spacing precisely. This localized design approach enables fine-tuned control over IC structure without requiring complex external control mechanisms.
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
This approach enables the precise control of IC structure and composition, promoting targeted immune responses and efficient delivery of payloads to target sites such as lymph nodes, spleen, and diseased tissues, while minimizing crosslinking and enhancing immune cell uptake.
Implementation Method 1
single-stranded NA handles for hybridization
Data Source
AI summary
An artificial immune complex (IC) free in solution, the artificial IC comprising a nucleic acid (NA) folding comprising stapled NA strands, the NA folding having an outer surface patterned with addressable sites and epitopes bound to the addressable sites and displayed in three dimensions for recruiting antibodies free in solution.