Gene Editing Nanocapsule with Tumor-Targeted Polymer Shell
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Solution Overview
Problem
Current gene editing technologies, such as CRISPR-Cas9, face challenges in safely and efficiently delivering the genome editing system into tumor cells due to issues like random DNA integration, protein stability, and off-target effects, particularly due to the difficulty in targeting and penetrating cell membranes.
Innovation Solution
A gene editing nanocapsule is developed, comprising a Cas/sgRNA ribonucleoprotein complex encapsulated in a polymer shell with tumor microenvironment-sensitive molecules, such as reduction-sensitive molecules, and a targeting agent like Angiopep-2, which allows for targeted release and enhanced cell endocytosis efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If CRISPR-Cas9 genome editing system is delivered using viral vectors or plasmids, then gene editing efficiency is improved, but random DNA integration occurs causing safety issues
Solution Approach 1:
The patent changes the physical state and delivery parameters of the CRISPR-Cas9 system by forming a ribonucleoprotein complex (RNP) instead of using plasmid DNA or viral vectors. This RNP complex can be directly delivered into cells, enabling gene editing without random integration events, thus resolving the safety issue while maintaining editing efficiency
Solution Approach 2:
The patent introduces a delivery vehicle or system as an intermediary to transport the Cas9 RNP complex into target cells. This intermediary enables controlled delivery of the editing machinery without the harmful random integration associated with viral or plasmid-based approaches
2Ease of operation
If protein and RNA are delivered without a carrier, then delivery simplicity is improved, but stability and cell membrane permeability deteriorate
Solution Approach 1:
The patent nests the Cas9 protein and sgRNA molecule together to form a ribonucleoprotein complex, where the RNA is bound within the protein structure. This nested configuration protects both components from degradation while maintaining their functional integrity, and the complex can be delivered as a single unit simplifying the delivery process
Solution Approach 2:
The patent employs a delivery vehicle or carrier system that acts as a protective shell around the Cas9 RNP complex. This flexible shell protects the fragile protein and RNA from the harsh physiological environment while enabling cell membrane penetration, thus improving stability and deliverability
3Productivity
If high concentration of Cas9 is used to improve editing efficiency, then gene editing efficiency is improved, but off-target effects increase
Solution Approach 1:
The patent employs a delivery system that enables dynamic, controlled release of the Cas9 RNP complex into target cells. This controlled delivery achieves sufficient intracellular concentration for efficient editing while avoiding the excessive dosing that causes off-target effects, thus resolving the contradiction between efficiency and specificity
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 nanocapsule achieves efficient and targeted gene editing in tumor cells with reduced off-target effects and improved biocompatibility, potentially leading to a safer and more effective gene therapy for tumors.
Implementation Method 1
the first monomer is a molecule capable of electrostatically binding with the Cas/sgRNA ribonucleoprotein complex
Implementation Method 2
the second monomer is a tumor microenvironment sensitive molecule
Data Source
AI summary
The present disclosure provides a gene editing nanocapsule and a preparation method and use thereof. The gene editing nanocapsule has a core-shell structure, wherein the inner core includes a Cas/sgRNA ribonucleoprotein complex, and the outer shell includes a polymer, the Cas/sgRNA ribonucleoprotein complex has a gene editing function, and the polymer acts as a carrier for the Cas/sgRNA ribonucleoprotein complex and protects it, because the polymer contains tumor microenvironment sensitive molecules, the nanocapsules can be efficiently released in tumor cells. Further, the surface of the outer shell can be modified with a targeting agent, so that the nanocapsule can specifically target tumor cells, which improves the endocytosis efficiency of the nanocapsule. The gene editing nanocapsule has good biocompatibility and biosafety, and is expected to become a safe and efficient gene therapy drug for tumors.