Modified Milk Exosomes for Stable Targeted Cargo Delivery
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Solution Overview
Problem
Existing methods for delivering cargo to mammalian cells face challenges in protecting the cargo from harsh physiological conditions and enzymatic degradation, and there is a need for effective delivery systems that can target specific cells or tissues.
Innovation Solution
The use of milk exosomes, modified to alter their biological membranes through enzymatic or glycan modifications, to encapsulate and deliver cargo such as miRNAs and therapeutic agents to specific mammalian cells or tissues, enhancing stability and targeting capabilities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If cargo is delivered directly to mammalian cells, then delivery efficiency is improved, but cargo stability against harsh physiological conditions and enzymatic degradation deteriorates
Solution Approach 1:
The patent uses exosomes as intermediary carriers to deliver cargo to mammalian cells. These exosomes protect the cargo from harsh physiological conditions and enzymatic degradation while enabling efficient cellular uptake. The exosome membrane acts as a protective barrier that maintains cargo stability during transport through the gastrointestinal tract and bloodstream, while still allowing for effective delivery to target cells.
Solution Approach 2:
The patent modifies exosome surface properties by altering glycoprotein composition and adding targeting ligands to change the physical and chemical parameters of the delivery system. These modifications enable the exosomes to resist degradation by proteases and to specifically target desired cells, thereby improving both cargo stability and delivery efficiency simultaneously.
2Productivity
If exosome membrane is modified to enhance targeting, then cellular uptake is improved, but structural integrity of exosome deteriorates
Solution Approach 1:
The patent applies local quality modification by selectively altering specific regions of the exosome membrane rather than the entire structure. Surface glycoproteins are modified at specific locations to add targeting ligands, while the overall exosome structure and core cargo remain intact. This localized approach maintains structural integrity while enhancing cellular uptake through targeted recognition.
Solution Approach 2:
The patent creates composite membrane structures by combining native exosome membrane components with added targeting ligands and modified glycoproteins. This composite approach allows the exosome to maintain its fundamental structural integrity while incorporating new functional elements that enhance cellular uptake and targeting specificity.
3Reliability
If exosomes are used for cargo delivery, then protection against degradation is improved, but targeting capability to specific cells deteriorates
Solution Approach 1:
The patent introduces dynamic adaptability to the exosome system by modifying surface glycoproteins to express different targeting ligands depending on the desired target cell type. This dynamic modification allows the same exosome delivery platform to be adapted for different therapeutic applications while maintaining its protective function against degradation throughout the delivery process.
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
Milk exosomes with modified membranes effectively protect and deliver cargo, increasing cellular uptake and stability, and can alter metabolism, gut microbiome, and enhance neurological processes, providing targeted therapeutic and nutritional benefits.
Implementation Method 1
The exosome is produced by contacting the naturally-occurring milk exosome with an enzyme capable of cleaving or covalently modifying a glycan on a surface glycoprotein of the exosome
Implementation Method 2
The uptake of the milk exosome into a mammalian cell is increased when the mammalian cell expresses a lectin that binds to a glycan on the surface of the milk exosome
Data Source
AI summary
The present disclosure relates to materials and methods for extracellular vesicle (e.g., exosome) -mediated delivery of cargo (e.g., endogenous and/or exogenous) to non-bovine mammalian (e.g., human) cells. For example, exosomes isolated from bovine milk for delivering cargo to non-bovine mammalian (e.g., human) cells are provided.