Lihong Wang-Bishop, Mohamed Wehbe, Lucinda E Pastora, Jinming Yang, Blaise R Kimmel, Kyle M Garland, Kyle W Becker, Carcia S Carson, Eric W Roth, Katherine N Gibson-Corley, David Ulkoski, Venkata Krishnamurthy, Olga Fedorova, Ann Richmond, Anna Marie Pyle, John T Wilson
Pharmacological activation of the retinoic acid-inducible gene I (RIG-I) pathway holds promise for increasing tumor immunogenicity and improving the response to immune checkpoint inhibitors (ICIs). However, the potency and clinical efficacy of 5'-triphosphate RNA (3pRNA) agonists of RIG-I are hindered by multiple pharmacological barriers, including poor pharmacokinetics, nuclease degradation, and inefficient delivery to the cytosol where RIG-I is localized. Here, we address these challenges through the design and evaluation of ionizable lipid nanoparticles (LNPs) for the delivery of 3p-modified stem-loop RNAs (SLRs)...
April 23, 2024: ACS Nano