Abstract: The present disclosure relates to heterologous exosomal vesicle proteins (HEVPs), engineered exosomes comprising HEVPs, and methods of preparing and using these compositions, including therapeutic applications.

Abstract: The instant application describes improved methods and compositions for the systemic delivery of therapeutic exosomes to a subject in need thereof. In certain embodiments, the current invention reduces the amount of exosomes delivered to liver, spleen and combinations thereof to allow greater distribution to other areas of the body such as, but not limited to, the brain, pancreas, lung, kidney, muscle. In certain embodiments, the methods involve the injection of one or multiple doses of non-therapeutic exosomes prior to the injection of a suitable therapeutic dose of exosomes with a therapeutic payload. Also included are methods to improve immune clearance of exosomes in subjects by inhibiting phagocytosis.

Abstract: Disclosed herein are compositions and methods comprising extracellular vesicles comprising nucleic acid that target genes, leading to macrophage polarization of tumor associated macrophages. In certain embodiments, disclosed herein are methods and compositions for increasing macrophage polarization for the treatment of cancer.

Abstract: The present disclosure provides a therapeutic method of treating cancer metastasis by inducing clearance of EVs using a binding agent specific to an EV protein. The method utilizes one or more binding agents specific to EV proteins, where the EV proteins are selected from prostaglandin F2 receptor negative regulator (PTGFRN); basigin (BSG); immunoglobulin superfamily member 2 (IGSF2); immunoglobulin superfamily member 3 (IGSF3); immunoglobulin superfamily member 8 (IGSF8); integrin beta-1 (ITGB1); integrin alpha-4 (ITGA4); 4F2 cell-surface antigen heavy chain (SLC3A2); a class of ATP transporter proteins (ATP1A1, ATP1A2, ATP1A3, ATP1A4, ATP1B3, ATP2B1, ATP2B2, ATP2B3, ATP2B4); CD13 (aminopeptidase N); MME (neprilysin), ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase family member 1); and NRP1 (neuropilin-1). Further provided herein includes a pharmaceutical composition for the treatment of cancer metastasis.

Abstract: Disclosed herein are extracellular vesicles comprising an immunomodulating component. Also provided are methods for producing the extracellular vesicles and methods for using the extracellular vesicles for treating cancer, GvHD, and autoimmune diseases.

Abstract: The present invention relates to methods of preparing a therapeutic exosome using a protein newly-identified to be enriched on the surface of exosomes. Specifically, the present invention provides methods of using the proteins for affinity purification of exosomes. It also provides methods of localizing a therapeutic peptide on exosomes, and targeting exosomes to a specific organ, tissue or cell by using the proteins. The methods involve generation of surface-engineered exosomes that include one or more of the exosome proteins at higher density, or a variant or a fragment of the exosome protein.

Abstract: Methods of loading extracellular vesicles with payload molecules via homogenization are disclosed herein.

Abstract: Disclosed herein are extracellular vesicles comprising an immunomodulating component. Also provided are methods for producing the extracellular vesicles and methods for using the extracellular vesicles for treating cancer, GvHD, and autoimmune diseases.

Abstract: The present invention relates to methods of preparing a therapeutic exosome using a protein newly-identified to be enriched on the surface of exosomes. Specifically, the present invention provides methods of using the proteins for affinity purification of exosomes. It also provides methods of localizing a therapeutic peptide on exosomes, and targeting exosomes to a specific organ, tissue or cell by using the proteins. The methods involve generation of surface-engineered exosomes that include one or more of the exosome proteins at higher density, or a variant or a fragment of the exosome protein.

Abstract: Described herein are novel rapid and reliable methods of detection of extracellular vesicles and quantifying extracellular vesicle concentrations and absolute number from various sources, including raw cell harvest. The methods described herein comprise detection of intrinsic fluorescence of extracellular vesicles in biological samples. Extracellular vesicles analyzed by the methods of this application have a stereotypical elution profile distinct from known contaminants. The methods described herein are a significant improvement over the state of the art and fulfills an unmet need in the field of extracellular vesicle manufacturing and quality control.

Abstract: Described herein are novel rapid and reliable methods of detection of extracellular vesicles and quantifying extracellular vesicle concentrations and absolute number from various sources, including raw cell harvest. The methods described herein comprise detection of light scattering of extracellular vesicles in biological samples. Extracellular vesicles analyzed by the methods of this application have a stereotypical elution profile distinct from known contaminants. The methods described herein are a significant improvement over the state of the art and fulfills an unmet need in the field of extracellular vesicle manufacturing and quality control.

Abstract: Disclosed herein are extracellular vesicles comprising an immunomodulating component. Also provided are methods for producing the extracellular vesicles and methods for using the extracellular vesicles for treating cancer, GvHD, and autoimmune diseases.

Abstract: Disclosed herein are extracellular vesicles comprising an immunomodulating component. Also provided are methods for producing the extracellular vesicles and methods for using the extracellular vesicles for treating cancer, GvHD, and autoimmune diseases.

Abstract: The present invention relates to methods of preparing a therapeutic exosome using a protein newly-identified to be enriched on the surface of exosomes. Specifically, the present invention provides methods of using the proteins for affinity purification of exosomes. It also provides methods of localizing a therapeutic peptide on exosomes, and targeting exosomes to a specific organ, tissue or cell by using the proteins. The methods involve generation of surface-engineered exosomes that include one or more of the exosome proteins at higher density, or a variant or a fragment of the exosome protein.

Abstract: Described herein are methods for the production of extracellular vesicles comprising culturing a population of producer cells in single-cell suspension, wherein the cells are cultured in chemically-defined culture medium, wherein the culture medium lacks animal-derived serum and animal-derived components; and obtaining from the cell culture an extracellular vesicle preparation comprising extracellular vesicles. In certain embodiments, the methods comprise perfusion culturing methods, including single-cell perfusion culturing methods and batch-refeed culturing methods. The methods described herein are a significant improvement over the state of the art and fulfills an unmet need in the field of extracellular vesicle manufacturing and quality control.

Abstract: The present invention relates to methods of preparing a therapeutic exosome using proteins newly identified to be enriched in the lumen of exosomes. Specifically, the present invention provides methods of localizing a therapeutic peptide or protein in exosomes. The methods involve generation of lumen-engineered exosomes that include one or more of the exosome proteins at higher concentrations, a modification or a fragment of the exosome protein, or a fusion protein of the exosome protein and a therapeutic or a cargo protein.

Abstract: Disclosed herein are compositions and methods comprising extracellular vesicles comprising nucleic acid that target genes, leading to macrophage polarization of tumor associated macrophages. In certain embodiments, disclosed herein are methods and compositions for increasing macrophage polarization for the treatment of cancer.

Abstract: Methods of loading extracellular vesicles with payload molecules via homogenization are disclosed herein.

Abstract: The present invention relates to methods of preparing a therapeutic exosome using a protein newly-identified to be enriched on the surface of exosomes. Specifically, the present invention provides methods of using the proteins for affinity purification of exosomes. It also provides methods of localizing a therapeutic peptide on exosomes, and targeting exosomes to a specific organ, tissue or cell by using the proteins. The methods involve generation of surface-engineered exosomes that include one or more of the exosome proteins at higher density, or a variant or a fragment of the exosome protein.

Abstract: Disclosed herein are compositions and methods comprising extracellular vesicles comprising nucleic acid that target genes, leading to macrophage polarization of tumor associated macrophages. In certain embodiments, disclosed herein are methods and compositions for increasing macrophage polarization for the treatment of cancer.