RESUMO
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
RESUMO
The etiology of acute diarrhea was studied in 915 children under 5 years of age between March 1986 and August 1987, in 7 hospitals in Tehran. 65 healthy children in similar age groups served as controls. Rotavirus was found in 25% of the patients and 1.5% of controls with the highest detection rate occurring in the 7-24 month age group [28%] and declining beyond 25 months of age [5%]. The infection rate was also high [19%] in the first 6 months of life and breast feeding was not protective. The rate of rotavirus infection was highest during the months of April and May [30% and 37% respectively] and lowest during December and January [7%]