Spherical Nucleic Acid Mixed CpG Shells for Controlled Co-Delivery
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Solution Overview
Problem
Existing spherical nucleic acids (SNAs) are limited to a single oligonucleotide sequence, which hinders efficient co-delivery of multiple oligonucleotide sequences to the same target cell, affecting applications in nucleic acid-based therapy and cancer immunotherapy.
Innovation Solution
Development of spherical nucleic acids (SNAs) comprising a nanoparticle core surrounded by a shell of mixed class A and B CpG oligonucleotides, enabling controlled co-delivery of distinct oligonucleotide sequences for enhanced therapeutic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If SNAs are prepared from a single oligonucleotide sequence, then the structure is simple and stable, but multiple oligonucleotide sequences cannot be co-delivered to the same target cell
Solution Approach 1:
The patent combines multiple distinct oligonucleotide sequences (class A CpG and class B CpG) into a single SNA structure, merging their functions into one delivery vehicle. This enables simultaneous co-delivery of multiple sequences to the same target cell, resolving the contradiction between delivery capability and structural simplicity.
Solution Approach 2:
The SNA structure is designed to perform multiple functions by incorporating different oligonucleotide sequences with distinct immunomodulatory activities. The single SNA particle can deliver class A CpG for Th1 response and class B CpG for adjuvant activity, achieving multi-functionality without requiring separate delivery systems.
2Reliability
If multiple oligonucleotide sequences are delivered separately, then each sequence can be optimized individually, but co-delivery to the same cell cannot be ensured
Solution Approach 1:
Multiple oligonucleotide sequences are merged into a single SNA structure during the preparation process. The covalent attachment of different oligonucleotides to the nanoparticle core ensures they remain together as one unit, guaranteeing co-delivery to the same cell while simplifying the manufacturing process compared to coordinating multiple separate deliveries.
Solution Approach 2:
The different oligonucleotide sequences are pre-assembled onto the nanoparticle core during SNA formation, before delivery to the target cell. This preliminary combination ensures that all sequences are already paired together in the correct ratios, eliminating the need for complex coordination during the delivery process.
3Adaptability or versatility
If a mixture of class A and class B CpG oligonucleotides is incorporated into SNAs, then controlled ratios enable synergistic immune responses, but the oligonucleotide shell composition becomes more complex
Solution Approach 1:
The patent controls the ratio of class A to class B CpG oligonucleotides as a key parameter during SNA preparation. By adjusting this parameter, the manufacturing process can be tuned to achieve desired immunomodulatory effects, such as optimizing the Th1 response while maintaining adjuvant activity, without requiring complex post-processing.
Data Source
AI summary
The present disclosure is directed to spherical nucleic acids (SNAs) comprising a nanoparticle core and an oligonucleotide shell attached to the external surface of the nanoparticle core, wherein the oligonucleotide shell comprises a mixture of class A CpG oligonucleotides and class B CpG oligonucleotides. The disclosure also provides methods of using the SNAs for, e.g., regulation of an immune response and gene regulation.