Programmed cell death 1 ligand 1 messenger RNA (PD-L1 mRNA) (PD-L1 mRNA)

Programmed cell death 1 ligand 1 (PD-L1) mRNA in hepatocytes is a therapeutic target for RNA interference (RNAi) therapies designed to treat chronic liver diseases and cancer. PD-L1, encoded by the CD274 gene, is an immune checkpoint protein that binds to PD-1 on T-cells to suppress immune responses (UniProt, 2024). In hepatocellular carcinoma (HCC) and chronic Hepatitis B (HBV), hepatocytes and tumor cells overexpress PD-L1 to create an immunosuppressive environment, leading to T-cell exhaustion (NCBI, 2023). Targeting the mRNA specifically in hepatocytes using GalNAc-conjugated siRNAs allows for the localized knockdown of PD-L1 protein expression, potentially restoring the activity of intrahepatic T-cells (PubMed, 2022). This approach aims to enhance the local anti-tumor or anti-viral immune response while avoiding the systemic immune-related adverse events often seen with anti-PD-L1 monoclonal antibodies. Clinical candidates like ARO-PDL1 have been developed to exploit this mechanism for treating solid tumors with liver involvement (Arrowhead Pharmaceuticals, 2021).

Other names

CD274 mRNAB7-H1 mRNAProgrammed death-ligand 1 mRNA

RNA interference (RNAi) mediated degradation of PD-L1 mRNA to reduce protein translation.