Environmentally Triggerable Retinoic Acid-Inducible Gene I Agonists Using Synthetic Polymer Overhangs
Retinoic acid-inducible gene I (RIG-I) is a cytosolic pattern recognition receptor (PRR) that potently activates antiviral innate immunity upon recognition of 5′ triphosphorylated double-stranded RNA (pppRNA). Accordingly, RNA ligands of the RIG-I pathway have recently emerged as promising antiviral agents, vaccine adjuvants, and cancer immunotherapeutics. However, RIG-I is expressed constitutively in virtually all cell types, and therefore administration of RIG-I agonists causes risk for systemic inflammation and possible dose-limiting toxicities. Here, we establish proof-of-concept and initial design criteria for pppRNA prodrugs capable of activating the RIG-I pathway in response to specific environmental stimuli. We show that covalent conjugation of poly(ethylene glycol) (PEG) to the 3′ end of the complementary strand, i.e., on the same side but opposite strand as the 5′ triphosphate group, can generate a synthetic overhang that prevents RIG-I activation. Additionally, conjugation of PEG through a clea...
Christian R. Palmer; Max E. Jacobson; Olga Fedorova; Anna M. Pyle; John T. Wilson
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Rohm and Haas Powder Coatings is delighted to announce that its Reading, Pennsylvania, facility is the first site in the world to receive the RCMS® Site Certification awarded by the American Chemical Council (ACC).
When Raj Gupta, Chairman and CEO of Rohm and Haas Company, became Chairman ... more