Genetically Engineered Microvesicles Carrying Suicide mRNA/Protein Inhibit Schwannoma Tumor Growth
Bolukbasi, Mehmet Fatih
Ozdener, Gokhan Baris
Erkan, Erdogan Pekcan
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CitationMizrak, Arda, Mehmet Fatih Bolukbasi, Gokhan Baris Ozdener, Gary J. Brenner, Sibylle Madlener, Erdogan Pekcan Erkan, Thomas Ströbel, Xandra O. Breakefield, and Okay Saydam. 2013. Genetically engineered microvesicles carrying suicide mRNA/protein inhibit schwannoma tumor growth. Molecular Therapy 21(1): 101-108.
AbstractMicrovesicles (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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