Robust expansion of dendritic cells in vivo by hydrodynamic FLT3L-FC gene transfer

•We engineered a novel FLT3L-immunoglobulin FC fusion construct.•The FC-domain improved the plasma pharmacokinetics profile of FLT3L.•Hydrodynamic gene transfer using FLT3L-FC DNA induced robust DC expansion in vivo.•FLT3L-FC protein produced in vivo spontaneously dimerized to enable FLT3 signaling.•Splenomegaly is an effective pharmacodynamic readout for FLT3L action in vivo.

Due to low numbers of endogenous dendritic cells (DCs) in vivo, exogenous DC-poietin Fms-like tyrosine kinase 3-ligand (FLT3L) is routinely used to generate DC for subsequent studies. We engineered a novel FLT3L-FC DNA construct that, when combined with hydrodynamic gene transfer (HDT), induced robust DC expansion in mice. DC generated in vivo by FLT3L-FC HDT produced cytokines in response to stimulation by an array of TLR agonists and promoted T cell proliferation. The FLT3L-FC protein produced in vivo spontaneously homodimerized to enable effective FLT signaling and the FC-domain enhanced its plasma half-life, providing an improved reagent and method to boost DC numbers.