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Exploiting Genetic Interference for Antiviral Therapy.

By Elizabeth J Tanner, Karla A Kirkegaard and Leor S Weinberger

Abstract

Rapidly evolving viruses are a major threat to human health. Such viruses are often highly pathogenic (e.g., influenza virus, HIV, Ebola virus) and routinely circumvent therapeutic intervention through mutational escape. Error-prone genome replication generates heterogeneous viral populations that rapidly adapt to new selection pressures, leading to resistance that emerges with treatment. However, population heterogeneity bears a cost: when multiple viral variants replicate within a cell, they can potentially interfere with each other, lowering viral fitness. This genetic interference can be exploited for antiviral strategies, either by taking advantage of a virus's inherent genetic diversity or through generating de novo interference by engineering a competing genome. Here, we discuss two such antiviral strategies, dominant drug targeting and therapeutic interfering particles. Both strategies harness the power of genetic interference to surmount two particularly vexing obstacles-the evolution of drug resistance and targeting therapy to high-risk populations-both of which impede treatment in resource-poor settings

Topics: Genetics, QH426-470
Publisher: Public Library of Science (PLoS)
Year: 2016
DOI identifier: 10.1371/journal.pgen.1005986
OAI identifier: oai:doaj.org/article:b3e949fd1b084a80b1624bf4549432e9
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