In recognition of his exceptional work to understand the chemistry of carbohydrates and the role they play in health and disease, Scripps Family Chair Professor Chi-Huey Wong of Scripps Research will receive the 2027 Alfred Bader Award in Bioinorganic or Bioorganic Chemistry.

The cutting-edge advances in multivalent mRNA–exosome vaccines provides a mechanistic blueprint showing how these customized mRNA payloads can systematically reprogram the immunosuppressive architecture of “cold” tumor microenvironments and mobilize potent, antigen-specific cytotoxic T-lymphocyte responses to overcome cancer immunotherapy resistance.A primary challenge in oncology vaccinology is delivering payloads to lymphoid-resident antigen-presenting cells (APCs) without triggering systemic toxicities or rapid hepatic clearance. While synthetic lipid nanoparticles (LNPs) are standard for systemic delivery, they face hepatocyte sequestration driven by blood-borne apolipoprotein E (ApoE) binding, which limits extrahepatic bioavailability. To bypass this constraint, engineered exosomes offer a biological alternative. These cell-derived vesicles feature a native lipid bilayer enriched with cholesterol and sphingomyelin that shields mRNA from ribonuclease degradation. By presenting surface markers like CD47—a “don’t eat me” signal blocking macrophage phagocytosis via SIRPα—exosomes achieve extended circulation half-lives (Figure 1).

Hepatocellular carcinoma (HCC) remains one of the most lethal malignancies worldwide, ranking as the third leading cause of cancer-related mortality, with limited therapeutic targets and dismal prognosis for advanced disease. This study identifies P53 and DNA damage-regulated gene 1 (PDRG1) as a novel oncogenic driver in HCC, revealing a previously unrecognized regulatory axis promoting tumor progression. The researchers demonstrate that PDRG1 expression is significantly upregulated in HCC tissues compared with normal liver, and that high PDRG1 expression correlates with advanced tumor stage, higher histological grade, and poor patient survival, establishing PDRG1 as a potential prognostic biomarker. Functional studies reveal that PDRG1 knockdown suppresses HCC cell proliferation, migration, and invasion in vitro, and inhibits tumor growth and lung metastasis in vivo, while PDRG1 overexpression exerts opposite effects. Mechanistically, PDRG1 activates Wnt/β-catenin signaling, elevating levels of β-catenin, c-Myc, and phosphorylated GSK-3β, and the oncogenic effects of PDRG1 are reversed by the Wnt pathway inhibitor XAV939, confirming functional dependence on this pathway. Furthermore, the study identifies transcription factor Specificity Protein 1 (SP1) as an upstream regulator that binds directly to the PDRG1 promoter and activates its transcription, with rescue experiments confirming that SP1 exerts its pro-tumor effects through PDRG1.

A new review in Medicine Plus traces the evolution of mRNA lipid nanoparticles (mRNA-LNPs) from prophylactic vaccine vehicles to programmable therapeutic platforms. The authors detail clinical and preclinical progress across infectious disease, cancer, autoimmunity, rare genetic disease and tissue repair, while identifying key translational hurdles including extrahepatic targeting, repeat-dose immunogenicity, off-target editing risks, and scalable manufacturing.