期刊
MOLECULAR THERAPY
卷 21, 期 1, 页码 101-108出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mt.2012.161
关键词
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资金
- NIH NCI [CA141150]
- NIH NINDS [NS037409]
- Forschungsgesellschaft for Brain Tumors
- EU-FP7-PEOPLE-2011-CIG
- Association for conduct of scientific research in the field of neonatology and pediatric intensive care: Unser Kind
- NATIONAL CANCER INSTITUTE [R01CA141150] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P01NS037409, P50NS037409] Funding Source: NIH RePORTER
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.
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