TY - JOUR PY - 2015// TI - enterovirus-like RNA construct for colon cancer suicide gene therapy JO - Iran. Biomed. J. A1 - Mahsa, Rasekhian A1 - Ladan, Teimoori Toolabi A1 - Safieh, Amini A1 - Kayhan, Azadmanesh SP - 124 EP - 132 VL - 19 IS - 3 N2 - In gene therapy, the use of RNA molecules as therapeutic agents has shown advantages over plasmid DNA, including higher levels of safety. However, transient nature of RNA has been a major obstacle in application of RNA in gene therapy. Here, we used the internal ribosomal entry site of encephalomyocarditis virus and the 3' non-translated region of Poliovirus to design an enterovirus-like RNA for the expression of a reporter gene [enhanced green fluorescent protein] and a suicide gene [thymidine kinase of herpes simplex virus]. The expression of these genes was evaluated by flow cytometry and cytotoxicity assay in human colorectal adenocarcinoma cell line [SW480]. We then armed RNA molecules with a target sequence for hsa-miR-143 to regulate their expression by microRNA [miRNA] mimics. The results showed effective expression of both genes by Entrovirus-like RNA constructs. The data also showed that the restoration of hsa-miR-143 expression in SW480 leads to a significant translation repression of the introduced reporter and suicide genes. Collectively, our data suggest the potential use of Entrovirus-like RNA molecules in suicide gene therapy. Additionally, as a consequence of the possible downregulated miRNA expression in cancerous tissues, a decreased expression of gene therapy constructs armed with target sequences for such miRNA in cancer tissue is expected

Language: en

LA - en SN - 1028-852X UR - http://dx.doi.org/ ID - ref1 ER -