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Mol Ther. 2013 Jan;21(1):101-8. doi: 10.1038/mt.2012.161. Epub 2012 Aug 21.

Genetically engineered microvesicles carrying suicide mRNA/protein inhibit schwannoma tumor growth.

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  • 1Department of Neurology and Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Abstract

Microvesicles (MVs) play an important role in intercellular communication by carrying mRNAs, microRNAs (miRNAs), non-coding RNAs, proteins, and DNA from cell to cell. To our knowledge, this is the first report of delivery of a therapeutic mRNA/protein via MVs for treatment of cancer. We first generated genetically engineered MVs by expressing high levels of the suicide gene mRNA and protein-cytosine deaminase (CD) fused to uracil phosphoribosyltransferase (UPRT) in MV donor cells. MVs were isolated from these cells and used to treat pre-established nerve sheath tumors (schwannomas) in an orthotopic mouse model. We demonstrated that MV-mediated delivery of CD-UPRT mRNA/protein by direct injection into schwannomas led to regression of these tumors upon systemic treatment with the prodrug (5-fluorocytosine (5-FC)), which is converted within tumor cells to 5-fluorouracil (5-FU)-an anticancer agent. Taken together, these studies suggest that MVs can serve as novel cell-derived "liposomes" to effectively deliver therapeutic mRNA/proteins to treatment of diseases.

PMID:
22910294
[PubMed - indexed for MEDLINE]
PMCID:
PMC3538300
Free PMC Article
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