Extracellular vesicles as biomarkers and therapeutics for neuromuscular disorders
Inventors
Hudson, Matthew B. • Selsby, Joshua T.
Assignees
University of Delaware • Iowa State University Research Foundation Inc
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Publication Number
US-12371653-B2
Publication Date
2025-07-29
Expiration Date
Abstract
This invention relates to extracellular vesicles and method of isolated tissue-specific extracellular vesicles from bodily fluids. The invention further relates to methods of using extracellular vesicles for diagnostic applications for detecting and monitoring diseases, conditions, and damage in a subject. The invention also relates to methods of using extracellular vesicles for therapeutic applications for treating diseases, conditions, and damage in a subject.
Core Innovation
The invention relates to a composition comprising extracellular vesicles comprising one or more therapeutic agents and/or RNA encoding the one or more therapeutic agents. The extracellular vesicles are isolated from cell culture medium of cultured HEK293 or HEK293T cells, and the one or more therapeutic agents and/or RNA encoding the one or more therapeutic agents are endogenous to the cultured HEK293 or HEK293T cells. The composition further includes extracellular vesicles carrying a targeting agent for targeting extracellular vesicles to muscle tissue.
In the composition, the cells are modified to contain a targeting agent such that the extracellular vesicles comprise the targeting agent that targets the extracellular vesicles to muscle tissue. The one or more therapeutic agents are not the targeting agent, and the cultured HEK293 or HEK293T cells have not been modified to contain higher levels of the one or more therapeutic agents and/or the RNA encoding the one or more therapeutic agents.
A related composition further provides extracellular vesicles comprising one or more therapeutic agents where the one or more therapeutic agents comprise viral vectors or plasmids. The extracellular vesicles are isolated from cell culture medium of cultured HEK293 or HEK293T cells comprising the one or more therapeutic agents, and the cells are modified to produce the therapeutic agents and to contain a targeting agent such that the extracellular vesicles comprise the targeting agent that targets the extracellular vesicles to muscle tissue, while the one or more therapeutic agents are not the targeting agent.
Claims Coverage
The partial claim set includes two independent claims. Each independent claim specifies extracellular vesicles from cultured HEK293 or HEK293T cells, a muscle-targeting targeting agent in the extracellular vesicles, and therapeutic cargo that is distinct from the targeting agent.
Endogenous therapeutic agents in HEK293/HEK293T-derived extracellular vesicles with muscle-targeting targeting agent
A composition comprising extracellular vesicles comprising one or more therapeutic agents and/or RNA encoding the one or more therapeutic agents, where the extracellular vesicles are isolated from cell culture medium of cultured HEK293 or HEK293T cells comprising the one or more therapeutic agents and/or the RNA encoding the one or more therapeutic agents; the one or more therapeutic agents and/or RNA encoding the one or more therapeutic agents are endogenous to the cultured HEK293 or HEK293T cells; and the cells are modified to contain a targeting agent such that the extracellular vesicles comprise the targeting agent that targets the extracellular vesicles to muscle tissue, wherein the one or more therapeutic agents are not the targeting agent, and the cultured HEK293 or HEK293T cells have not been modified to contain higher levels of the one or more therapeutic agents and/or the RNA encoding the one or more therapeutic agents.
Viral vector or plasmid therapeutic agents in HEK293/HEK293T-derived extracellular vesicles with muscle-targeting targeting agent
A composition comprising extracellular vesicles comprising one or more therapeutic agents, where the extracellular vesicles are isolated from cell culture medium of cultured HEK293 or HEK293T cells comprising the one or more therapeutic agents; the one or more therapeutic agents comprise viral vectors or plasmids; the cells are modified to contain a targeting agent such that the extracellular vesicles comprise the targeting agent that targets the extracellular vesicles to muscle tissue; wherein the one or more therapeutic agents are not the targeting agent; and wherein the cultured HEK293 or HEK293T cells are modified to produce the therapeutic agents.
Across both independent claims, the inventive scope centers on extracellular vesicles produced from cultured HEK293/HEK293T cells that include a muscle-targeting targeting agent in the vesicles while carrying therapeutic agents, either endogenous therapeutic agents and/or RNA encoding them, or viral vectors or plasmids produced by modified cells.
Stated Advantages
Documented Applications
Liquid-biopsy diagnostics for neuromuscular disorders using muscle-derived extracellular vesicles, including detect, monitor, risk determination, monitoring progression, and monitoring treatment effectiveness.
Therapy involving extracellular vesicle delivery of therapeutic proteins, RNAs, and viral vectors or plasmids, including targeting agents and delivery of full-length dystrophin with sarcolemmal localization.
Capture and characterization of satellite cell extracellular vesicles, including uptake by myotubes and reversal of peroxide-induced mitochondrial dysfunction.
Delivery verification and profiling of extracellular vesicle cargo, including mRNA cargo characterization and proteomics or mass spectroscopy cargo profiling in extracellular vesicles.
Packaging and detection of AAV in extracellular vesicles.
Delivery of extracellular vesicle cargo to cardiac cells and in Langendorff perfused heart contexts.
Delivery of extracellular vesicle protein to brain contexts with quantification of muscle-derived extracellular vesicles in saliva.
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