Controlled Biomolecule Expression for Lumen-Loaded BioNVs and Exosomes
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Solution Overview
Problem
Current methods for packaging therapeutically relevant biomolecules into delivery systems like AAVs and lipid nanoparticles are limited by concentration and variety, and naturally shed exosomes have less desirable and less controllable concentrations, necessitating a method to control and regulate genetic expression for effective disease treatment.
Innovation Solution
A method involving obtaining hypoimmunogenic cells, activating them to express therapeutically relevant biomolecules, and processing these cells to generate therapeutic biomimetic nanovesicles or exosomes that encapsulate these biomolecules, utilizing cells such as stem cells or engineered T cells with reduced immunogenic proteins and increased expression of immunoprotective proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If spontaneous inclusion of biomolecules into CDV lumen is used, then the process is simple, but the concentration and variety of packaged biomolecules are limited and uncontrollable
Solution Approach 1:
The patent applies preliminary action by pre-activating cells to express desired biomolecules before CDV formation, and by pre-segmenting concentration chambers to prepare controlled loading environments. This ensures that when CDVs form, the biomolecules are already present at controlled concentrations in the correct compartments, resolving the contradiction between simple loading and precise concentration control.
2Manufacturing precision
If segmented concentration chambers are used during BioNV formation, then controlled loading is achieved, but the process complexity increases
Solution Approach 1:
The patent applies self-service by enabling cells to autonomously express and package biomolecules into CDVs through their natural cellular machinery. The segmented concentration chambers are designed to work with cellular self-organization, allowing cells to automatically sort and package biomolecules based on their properties without requiring complex external control mechanisms, thus reducing overall system complexity while maintaining precision.
3Reliability
If naturally shed exosomes are used, then the therapeutic potential is present, but the concentration of biomolecules is less desirable and less controllable
Solution Approach 1:
The patent applies preliminary action by pre-activating cells to express specific biomolecules at controlled levels before exosome formation occurs. This ensures that when exosomes are naturally shed, they contain the desired biomolecules at predetermined concentrations, combining the natural therapeutic benefits of exosomes with precise concentration control that was previously unattainable.
4Adaptability or versatility
If genetic expression is activated to increase biomolecule variety, then therapeutic relevance improves, but immunogenicity increases
Solution Approach 1:
The patent applies local quality by differentiating between cell types used for biomolecule production and those used for delivery. Engineered cells with high biomolecule variety serve as factories to produce CDVs, which then serve as delivery vehicles. The delivery CDVs are engineered to be hypoimmunogenic through selective gene editing, thus providing high biomolecule variety in the therapeutic payload while maintaining low immunogenicity in the delivery vehicle itself.
Data Source
AI summary
Disclosed herein are methods of generating therapeutic biomimetic nanovesicles (BioNVs) or therapeutic exosomes with lumen-loaded, therapeutically relevant biomolecules from hypoimmunogenic cells, compositions of therapeutic BioNVs or therapeutic exosomes, and methods of using the same for treatment or prevention of a disease or disorder.