ARMM Microvesicle Retinal Delivery With Lower Immune Response
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Solution Overview
Problem
Current delivery systems for therapeutic agents to the retina face challenges such as limited packaging capacity, immune response triggers, and inefficiency in delivering proteins and nucleic acids, particularly for treating genetic retinal disorders.
Innovation Solution
Utilizing ARRDC1-mediated microvesicles (ARMMs) for targeted delivery of therapeutic agents, such as proteins and nucleic acids, to the retina by incorporating viral envelope proteins for cell attachment and minimizing immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If viral vectors are used for delivery, then delivery efficiency is improved, but immune response is triggered
Solution Approach 1:
The patent uses ARRDC1-mediated microvesicles as an intermediary delivery system that mimics viral efficiency without triggering immune responses. These microvesicles serve as a mediator between the therapeutic cargo and retinal cells, achieving effective delivery while avoiding the harmful immune activation associated with direct viral vector use.
2Quantity of substance
If packaging capacity is increased, then more therapeutic agents can be delivered, but delivery system complexity increases
Solution Approach 1:
The patent segments the delivery system into modular components: ARRDC1-mediated microvesicles that can be loaded with various therapeutic agents. This segmentation allows flexible packaging capacity adjustment by selecting appropriate microvesicle sizes and cargo loads without redesigning the entire delivery system, thereby managing complexity while maintaining capacity.
3Reliability
If targeted delivery to retinal cells is achieved, then treatment efficacy is improved, but delivery system specificity requirements increase
Solution Approach 1:
The patent applies local quality by engineering specific properties into the microvesicles for retinal targeting. The delivery system incorporates retinal-specific targeting mechanisms (such as ligand-receptor interactions or tissue-specific uptake pathways) that confer localized effectiveness to retinal cells while maintaining simplicity in other aspects of the system design.
Data Source
AI summary
The present invention provides methods, systems, and compositions for ARMM-mediated delivery of molecules of interest (e.g., therapeutic agents) to cells and tissues of the eye. The present invention further relates to compositions and methods of producing, testing, and administering ARRDC1-mediated microvesicles (“ARMMs”) to internal structures of the eye. More particularly, the present invention provides compositions and methods of producing, testing, and administering ARMMs particles comprising one or more therapeutic agents (e.g., biological molecules including, but not limited to, CRISPR/Cas9 and other similar endonucleases, base editors, small molecules, proteins, and nucleic acids (e.g., DNA, RNA, siRNA, mRNA, miRNA, and the like)). Also provided are methods of administering therapeutic agents associated with ARMMs, including, but not limited to, methods of treating or contacting cells and tissues of the eye in one or more dosing regimens. In particular, the present invention provides methods of administering therapeutic agents via ARMMs to the cells and tissues that comprise the retina or into the subretinal space. Additionally, the present invention relates to methods of manufacturing (e.g., culturing, clarifying, separating, and concentrating) the inventive compositions from stable producer cell lines and from cell cultures.