Location: Plant Genetics Research
Project Number: 5070-31320-001-018-A
Project Type: Cooperative Agreement
Start Date: Sep 24, 2025
End Date: Sep 23, 2026
Objective:
Objective 1: Evaluate anti-influenza strategies based on competition for RNA-dependent RNA replication.
Objective 2: Evaluate anti-influenza strategies based on competition for segment bundling and/or packaging.
Objective 3: Evaluate anti-influenza strategies based on disruption of cellular functions of influenza infected cells.
Approach:
The overall approach is to leverage natural mechanisms that used by influenza to disrupt the viral life cycle. This effort requires acquisition of new knowledge, and methods to test for utility as genome edits. Three projects will be performed independently to 1) study, modify, and develop strategies for disruption of viral replication, 2) study, modify, and develop strategies for disruption of viral segment bundling and/or packaging, and 3) develop and use methods to identify host alleles that can be used to disrupt the viral life cycle.
Specific Projects:
Evaluate anti-influenza strategies based on competition for RNA-dependent RNA replication. We have recently developed methods to provide for influenza-dependent RNA replication. We will design, build, and test replicons an ability to compete with viral replication. Promising methods will be evaluated for the potential to limit influenza replication and transmission.
Evaluate anti-influenza strategies based on competition for segment bundling and/or packaging. Many viruses can be completely inhibited by modified viral genomes that directly disrupt genome bundling or viral packaging. We have developed methods to produce such modification within mammalian cells. We will develop new viral segment variants that can be used to inhibit segment bundling and/or packaging.
Evaluate anti-influenza strategies based on disruption of cellular functions of influenza infected cells. We have also recently developed methods to provide for influenza-dependent RNA transcription from transgene-expressed mRNAs. This strategy will be leveraged to facilitate disruption of the viral life-cycle through expression of host, viral, or exogenous alleles that can prevent or reduce cellular functions that are required by influenza.