Nested Nanoshell Delivery for Precise CRISPR Gene Editing
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Solution Overview
Problem
Current treatments for inflammation and pain lack effective and sustained delivery mechanisms, and existing gene editing technologies face challenges in precise spatial and temporal control within cells.
Innovation Solution
The use of nanoshells and macroshells with immune shielding surfaces, encapsulating CRISPR-Cas9 systems and engineered stem cells, for targeted delivery and expression of therapeutic proteins to reduce inflammation and pain, and for treating diseases like Alzheimer's and cancer, by enabling precise gene editing and immune evasion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If CRISPR-Cas9 systems are delivered to cells for gene editing, then precise gene editing capability is improved, but delivery precision and temporal control within specific cell types deteriorate
Solution Approach 1:
The patent employs a hierarchical delivery system where macroshells contain multiple nanoshells, which in turn encapsulate CRISPR-Cas9 components. This nested structure enables sequential targeting: macroshells first target specific tissue types, then nanoshells within them target specific cell types, achieving precise spatial and temporal delivery control while maintaining gene editing capability
Solution Approach 2:
The delivery system is divided into distinct functional components: macroshells for initial targeting and stabilization, nanoshells for cellular-level targeting, and encapsulated CRISPR-Cas9 complexes for gene editing. This segmentation allows each component to optimize its specific function while working together to achieve precise delivery and editing
2Reliability
If therapeutic proteins are delivered to reduce inflammation and pain, then treatment effectiveness is improved, but delivery duration and sustained release capability deteriorate
Solution Approach 1:
The multi-layered shell system provides sustained release of therapeutic proteins through continuous diffusion and controlled degradation of the shell materials. The macroshells and nanoshells are designed to degrade progressively, maintaining therapeutic protein release over extended periods, thus achieving both high effectiveness and long duration of action
Solution Approach 2:
The patent utilizes flexible biodegradable polymer shells that can gradually degrade in the physiological environment. This flexibility allows the shells to maintain structural integrity for initial protection while enabling controlled release of therapeutic proteins over time through progressive degradation, extending delivery duration
3Reliability
If nanoshells and macroshells with immune shielding surfaces are used for targeted delivery, then immune evasion and therapeutic stability are improved, but device complexity and manufacturing difficulty deteriorate
Solution Approach 1:
The shells are constructed from composite materials combining biodegradable polymers with immune-evasive coatings such as PEG (polyethylene glycol) or biomimetic surfaces. This composite approach provides both the structural framework for targeted delivery and the immune shielding properties, achieving enhanced reliability without proportionally increasing manufacturing complexity
4Productivity
If stem cells are engineered for tissue regeneration, then regenerative capability is improved, but control precision and targeted delivery to specific locations deteriorate
Solution Approach 1:
The nanoshell-macroshele system acts as an intermediary carrier that binds to stem cells or delivers genetic materials to stem cells. This intermediary approach enables precise targeting of stem cells to specific injury sites while maintaining their regenerative capabilities, as the shells provide directional guidance without compromising stem cell function
Data Source
AI summary
An engineered dendritic cell including a nanostructure, RNAi based logic circuit, a CRISPR-Cas9 system/light activated CRISPR-Cas9 system (or a modulating CRISPR-Cas9 system) and a sensing protein and/or an activating protein for enhanced interaction with a T-cell and/or a natural killer cell against a particular type of cancer cells is disclosed. The engineered dendritic cell can be ex vivo or in vivo (implanted as a biodegradable/biocompatible lymph node). Furthermore, the CRISPR-Cas9 system can be replaced by Cas9-HFI or Cas12a or a transposon-encoded CRISPR-Cas system.