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Review
. 2018 Oct 2;4(4):25.
doi: 10.3390/ncrna4040025.

MicroRNA-Attenuated Virus Vaccines

Elizabeth J Fay  1   2 , Ryan A Langlois  3   4   5
Affiliations
Review

MicroRNA-Attenuated Virus Vaccines

Elizabeth J Fay et al. Noncoding RNA. .

Abstract

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.

Keywords: RNAi; live-attenuated vaccine; siRNA.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Tissue- and species-specific microRNA-attenuated viruses. (A) Model of tissue-specific attenuation of a flavivirus combined with attenuation in an insect vector. (B) Model depicting generation of a miRNA-attenuated influenza A virus in miRNA knock out cells to generate a species-universal attenuated vaccine. Created with BioRender (Toronto, ON, Canada).
Figure 2
Figure 2
Altered viral genome structures to improve miRNA targeting. (A) Model of the wild type Langat virus genome, highlighting the capsid gene (top), the miRNA-targeted (purple) duplicated 5’ region followed by a 2A site (orange) to allow for expression of the codon-optimized capsid protein (middle), and the insertion of an IRES to regulate the expression of the capsid protein (bottom). (B) The wild type influenza virus NP gene (top) and the miRNA-targeted (purple) NP gene with a duplicated packaging signal (bottom). Created with BioRender (Toronto, ON, Canada).
See this image and copyright information in PMC

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