Design therapeutics to transiently manipulate host genes to facilitate viral clearance
Manipulating host genes to promote immune mediated viral clearance
Our approach is to manipulate host genes rather than viral genes to promote an immune response in our LCMV clone 13 infection model. We use several validated techniques to manipulate candidate host genes and promote immune clearance of virus in our mouse model of chronic infection. These techniques include linking siRNA to single chain antibodies to target host genes in specific cells in vivo. We also target genes that we have identified as being important in dendritic cells (DCs) and macrophages with customized siRNA–loaded nanoparticles that also capture and neutralize virus to promote antigen presentation. Our work focuses on how genetic manipulation of mouse and human DCs affects their functional capacity and their ability to survive and prime T cells. Similarly we investigate how genetic manipulation of human and mouse T cells affects their ability to produce cytokines, degranulate and kill target cells in the face of persistent infection.