Nanoparticle-Protein Complex for Intracellular Delivery
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Solution Overview
Problem
Current methods for intracellular protein delivery face challenges such as long-term gene expression, random genome incorporation leading to cancer, inefficient protein delivery due to size and charge variations, and trapping in endosomes, limiting the delivery of proteins to specific organelles.
Innovation Solution
A nanoparticle-protein complex comprising a gold nanoparticle with an amine-containing ligand and a protein with a carboxylic acid-containing tag, allowing for efficient self-assembly and delivery of proteins and nucleic acids into cells, bypassing endosomal entrapment and enabling targeted organelle delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If gene delivery is used to deliver protein into cells, then protein function can be achieved, but the gene permanently incorporates into the genome causing long-term expression and potential cancer
Solution Approach 1:
The invention extracts only the necessary protein product from the gene, delivering it directly to cells without the gene itself. This separates the beneficial protein function from the harmful genomic integration, allowing temporary protein expression without permanent genetic modification or cancer risk
Solution Approach 2:
The invention uses a delivery vehicle as an intermediary to transport the protein across the cell membrane. This mediator enables direct protein delivery without requiring gene transfection, thus avoiding genomic incorporation while still achieving intracellular protein function
2Duration of action of stationary object
If direct protein delivery is used, then long-term expression issues are avoided, but the protein cannot freely diffuse through the cell membrane due to its large size
Solution Approach 1:
A delivery vehicle serves as an intermediary carrier that binds to the protein and facilitates its transport across the cell membrane. This mediator overcomes the size barrier, enabling large proteins to enter cells without requiring genetic expression or viral vectors
3Reliability
If conventional delivery vehicles are used, then certain proteins can be delivered, but delivery is limited to specific proteins due to size and charge variations
Solution Approach 1:
The delivery vehicle is designed with universal binding capabilities that can accommodate proteins of varying sizes and charges. The vehicle's surface properties allow it to bind different protein types through multiple interaction mechanisms, making it a versatile platform for delivering any protein of interest rather than being limited to specific protein types
4Ease of operation
If protein delivery vehicles are used, then proteins can be transported into cells, but proteins get trapped in endosomes that degrade them and restrict access to destination organelles
Solution Approach 1:
The delivery vehicle is pre-engineered with properties that enable it to escape endosomes after cellular uptake. This preliminary design feature ensures that once inside the cell, the vehicle can actively escape the endosomal compartment and release the protein at the correct intracellular destination, preventing degradation and ensuring proper localization
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 nanoparticle-protein complex facilitates efficient and versatile intracellular delivery of various proteins and nucleic acids, including CRISPR-Cas9 for genome editing, with high specificity and minimal off-targeting, overcoming previous limitations in protein delivery methods.
Implementation Method 1
a nanoparticle including an amine-containing ligand... a protein including a carboxylic acid-containing tag
Data Source
AI summary
Various embodiments disclosed relate to a nanoparticle-protein complex for intracellular protein delivery. In various embodiments, the present invention provides a nanoparticle-protein complex including a nanoparticle including an amine-containing ligand. The nanoparticle-protein complex also includes a protein comprising a carboxylic acid-containing tag.