Live-attenuated vaccines are the most effective way to establish robust, long-lasting immunity against viruses. However, the possibility of reversion to wild type replication and pathogenicity raises concerns over the safety of these vaccines. The use of host-derived microRNAs (miRNAs) to attenuate viruses has been accomplished in an array of biological contexts. The broad assortment of effective tissue- and species-specific miRNAs, and the ability to target a virus with multiple miRNAs, allow for targeting to be tailored to the virus of interest. While escape is always a concern, effective strategies have been developed to improve the safety and stability of miRNA-attenuated viruses. In this review, we discuss the various approaches that have been used to engineer miRNA-attenuated viruses, the steps that have been taken to improve their safety, and the potential use of these viruses as vaccines.
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