Exploiting host microRNAs to control virus replication. This research area was the result of a study focused on determining whether host miRNAs contributed to the cellular response to virus infection. Upon determining that miRNAs were not inherently antiviral, it became clear that they could be engineered to perform this function. In brief, because miRNAs, like mRNAs, can demonstrate tissue-specificity, one can exploit their expression to impact virus biology in a manner akin to the RNAi response. By incorporating fully complementary miRNA target sites into a given virus, one can silence the microbe in any tissue, cell, or species where that small RNA is present without modifying the pathogen at a protein level. We have used this concept to address vaccine manufacturing problems, ascertain the role of hematopoieitic cells in the response to virus infection, define the cells responsible for systemic spread of virus, and as a means of generating an added level of biocontainment to exceptionally dangerous microbes.