Particulate drug carriers can be used to deliver encapsulated drugs to diseased tissues or organs within our body. We have used, for example, ligand conjugated liposomes to target tumors, the kidney, or to achieve transport across the blood-brain barrier. More recently, we have focused on gene delivery to hepatocytes as a promising treatment option for monogenic metabolic diseases. To this end, lipid nanoparticles (LNPs) are designed, which are inspired by the lipid composition of enveloped viruses. They comprise ionized or ionizable lipids for DNA complexation and an array of helper lipids for structural integrity, for steric stabilization, and to promote cellular uptake, membrane fusion, and intracellular processing. LNPs are combined with nanovector plasmid DNA constructs, which allow for a lifetime transfection of target cells. Targeting strategies are evaluated using a broad array of physico-chemical and analytical methods in combination with cell culture based in vitro models. Zebrafish embryos are used as a vertebrate screening model to identify well tolerated LNPs with favorable pharmacokinetic properties and a high transfection efficiency in vivo. If successful, this platform technology will be the first step towards a future clinical implementation of LNP based hepatic gene delivery strategies.