"In some embodiments, the purified populations and compositions provided herein are useful in the treatment of a cancer or other neoplastic condition, such as, for example, gliomas and other cancers of the central nervous system.
"In some embodiments, the purified populations of microvesicles associated with a packaged or otherwise associated viral vector is an ingredient (e.g., population of MAV as the active ingredient) in a pharmaceutically acceptable composition and/or formulation suitable for administration to the subject. Generally these compositions and formulations comprise a pharmaceutically acceptable carrier for the active ingredient. The specific carrier will depend upon a number of factors, including for example, the route of administration.
"In some embodiments, the invention includes a purified population of microvesicles that contain or are otherwise associated with one or more viral particles, wherein the microvesicle is shed or otherwise produced by a producing cell. In some embodiments, the microvesicles are associated with the viral particles through a covalent interaction. In some embodiments, the microvesicles are associated with the viral particles through a non-covalent interaction. In some embodiments, the producer cell naturally sheds the microvesicles. In some embodiments, the producer cell has been modified to shed the microvesicles. In some embodiments, the viral particle is or is derived from adenovirus, lentivirus, herpes virus, and adeno-associated virus (AAV). In some embodiments, the microvesicle comprises a lipid membrane having an outer surface that has been modified to include or express a receptor ligand or bridging molecule linked to a receptor ligand that targets a desired cell type. In some embodiments, the desired target cell type is different that the cell type that is target by a microvesicle having an unmodified lipid membrane. In some embodiments, the population of microvesicles comprises about 10.sup.9 to 10.sup.13 genome copies. In some embodiments, the viral particle comprises a nucleic acid encoding a peptide, polypeptide or protein. In some embodiments, the viral particle comprises a non-native nucleic acid.
"In some embodiments, the invention provides methods of producing a purified population of microvesicles that contain viral particles by engineering a cell that sheds microvesicles, wherein the cell is engineered to comprise a viral vector and a nucleic acid encoding a desired polypeptide under the control of the viral nucleic acids necessary for expression of the desired polypeptide. The nucleic acid sequence can include or be accompanied by accessory nucleic acid sequences, i.e., sequences needed for the expression of the nucleic acid sequence. These accessory nucleic acid sequences include, for example, promoters, positive regulatory elements and negative regulatory elements. In some embodiments, the method also includes the step of increasing production of microvesicles by exposing the engineered cell to a stimulus or by genetically engineering the engineered cell to increase production of the microvesicles. In some embodiments, the stimulus is a chemical stressor or an environmental stressor. In some embodiments, the method also includes the step of increasing transfection efficiency of the viral particles. In some embodiments, the engineered cell is further modified to express a targeting protein on an outer surface of the microvesicle.
"In some embodiments, the invention provides uses of the purified populations of microvesicles that are associated with viral particles in the treatment of a disorder in a subject. In some embodiments, the subject is human. In some embodiments, the disorder is a cancer. In some embodiments, the cancer is a cancer of the central nervous system (CNS).
BRIEF DESCRIPTION OF THE DRAWINGS
"FIG. 1 is a graph depicting how AAV purified by standard techniques does not pellet efficiently using the centrifugation speed used for microvesicle pelleting.
"FIG. 2 is a graph depicting the ability of AAV associated-microvesicles to efficiently transduce cells in culture.
"FIGS. 3A and 3B are an illustration and a graph depicting the ability of AAV associated-microvesicles to efficiently transduce cells in vivo.
"FIGS. 4A-4E are a series of illustrations depicting the use of anti-AAV immunogold labeling in the detection of microvesicle-associated vectors. In these illustrations, the arrows are indicating the location of AAV (AAV1 or AAV2) that is 'free,' i.e., outside of a microvesicle, the triangles are indicating the location of AAV (AAV1 or AAV2) inside a microvesicle, and the diamond-headed arrows are indicating the location of AAV (AAV1 or AAV2) that is bound to surface of a microvesicle. FIGS. 4A and 4B depict the isolation and identification of AAV1 MAV, while FIGS. 4C-4E depict the isolation and identification of AAV2 MAV."
For more information, see this patent application: Skog,
Keywords for this news article include: Antigen-Presenting Cells, Biotechnology, Glioma, Viruses, Genetics, Oncology, Peptides, Virology, Treatment, Immunology, Proteomics, Amino Acids, Nanoparticle, Streptavidin, Therapeutics, Bioengineering, Blood Proteins, Nanotechnology, Viral Vaccines, Cancer Vaccines, Dendritic Cells, Immunoglobulins, Serum Globulins.
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