"The purified populations of microvesicles associated with a viral particle are useful to deliver a nucleic acid to a cell. In some embodiments, the cell is within the body of an individual. The cell to which the nucleic acid gets delivered is referred to as the target cell. The viral particle can be engineered to contain a nucleic acid that it would not naturally contain (i.e. which is exogenous to the normal content of the viral particle). In some embodiments, the cell which produces the microvesicle for administration is of the same or similar origin or location in the body as the target cell. For example, for delivery of a microvesicle to a brain cell, the cell which produces the microvesicle would be a brain cell (e.g. a primary cell grown in culture). In other embodiments, the cell which produces the microvesicle is of a different cell type than the target cell. In one embodiment, the cell which produces the microvesicle is a type that is located proximally in the body to the target cell.
"The nucleic acid sequence which can be delivered to a cell via a microvesicle and associated viral vector can be RNA or DNA, and can be single or double stranded, and can be selected from a group comprising: nucleic acid encoding a protein of interest, oligonucleotides, nucleic acid analogues, for example peptide-nucleic acid (PNA), pseudo-complementary PNA (pc-PNA), locked nucleic acid (LNA) etc. Such nucleic acid sequences include, for example, but are not limited to, nucleic acid sequences encoding proteins, for example that act as transcriptional repressors, antisense molecules, ribozymes, small inhibitory nucleic acid sequences, for example but are not limited to RNAi, shRNA, siRNA, miRNA, antisense oligonucleotides, and combinations thereof. 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.
"The microvesicles are shed from cells referred to herein as 'producer cells.' The producer cells can naturally shed one or more types of microvesicles. Alternatively or in addition, the producer cells can be modified, e.g., genetically engineered or otherwise modified using compounds that can affect microvesicle secretion and/or production, to shed one or more desired types of microvesicles.
"Suitable producer cells for use in the purified microvesicle populations, compositions and methods of the invention include, by way of non-limiting example, cells such as 293T (ATCC, see also Biotechniques. 2003 January; 34(1):184-9); Per.C6 (
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