The development of oligonucleotide therapeutics such as siRNA and mRNA depends on physiologically relevant cell systems that can support high-throughput screening (HTS) for target discovery and downstream validation. Primary hepatocytes are the gold standard in vitro model for drug metabolism and allow liver targeted drug development due to their retention of key hepatic functions in vitro. Despite their proven utility for small molecule discovery, technical challenges with achieving efficient and reproducible transfections have historically limited primary hepatocyte use in mRNA and siRNA-based high-throughput applications.
