Use of microRNA strategy for targeting oncolytic viruses to cancer cells
Use of microRNA strategy for targeting oncolytic viruses to cancer cells
Mohammad Shayestehpour,1,*Faezeh Ebneali,2Zahrasadat Fateminasab,3
1. Department of Microbiology and Immunology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran 2. Department of Microbiology and Immunology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran 3. Department of Microbiology and Immunology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran
Introduction: Cancer, as one of the most serious public health problems, is the second-leading cause of death in the world after cardiovascular disease. The number of patients and mortality are increasing worldwide; therefore, early diagnosis, prevention, and effective treatment of cancer are very important. Current treatments such as chemotherapy and radiation therapy are often non-selective and have side effects. The use of oncolytic viruses (viral therapy) is a new approach to treating cancer. One problem with viral therapy is the lack of selective replication for the virus in cancer cells, meaning that the virus replicates in normal cells. In recent years, various methods have been used to inhibit virus replication in healthy cells and to make selective replication in tumors. Correspondingly, miRNA targeting is the newest method. The present study describes the different aspects of making selectivity for replication of oncolytic viruses by the miRNA targeting mechanism.
Methods: We searched PubMed, web of science, Scopus, google scholar and ProQuest databases to find articles which were used from microRNA strategy for targeting oncolytic viruses to cancer cells. All articles were collected, studied and analyzed by two researchers.
Results: Adenovirus type 5 is targeted to pancreatic cancer cells by insertion of 8 copies of miR-148a and miR-216a target sequences to the viral genome. Oncolytic adenovirus type 5 is targeted to breast cancer cells by microRNA-145 and to hepatocarcinoma by microRNA-199, microRNA-143, microRNA-148a and microRNA- let-7. Four copies of miR-122 complementary sequences were inserted at E1A gene of adenovirus 6 to target it toward liver cancer cells. Six miR-124 target sequences were introduced to genome of oncolytic Semilki Forest Virus for increasing its selectivity. microRNA target sequences complementary to miR-124, miR-125, miR-133 and miR-208 were inserted into the Mengovirus genome to make a more selective virus. A let-7 MicroRNA-sensitive vesicular stomatitis virus showed tumor-specific replication. Inserting target sequences of miR-122, miR-7 and miR-148a to measles virus genome could target it to pancreatic cancer cells. miRNA-145 regulated oncolytic herpes simplex virus-1 (HSV-1) selectivly was killed human non-small cell lung cancer cells. MicroRNA modification of Coxsackievirus B3 (miR-145/miR-143) was decreased its toxicity, while retaining oncolytic potency against lung cancer.
Conclusion: microRNA targeting strategy is an acceptable method for attenuation of oncolytic viruses in normal cells and for increasing selective replication in tumor cells. This strategy can be used to make a more specific oncolytic virus that only targets cancer cells.