Development of Anti-COVID RNAi Therapeutics Using Human iPSC-Derived Alveolar Epithelial Cells

SARS-CoV-2 induced COVID-19 is a deadly health hazard for all Californians, Americans and the world. New SARS-CoV-2 Variants of Concern, including Delta and Delta+, as well as future variants are a significant concern for public health. RNAi therapeutics have the potential to target each and every SARS-CoV-2 variant, including Delta. However, due to a rate-limiting delivery problem, we cannot yet deliver RNAi therapeutics into lung cells of patients. Our research proposed develop an entirely new type of molecule to directly addresses the RNAi delivery problem. While we did not make as much headway as we thought we would when we proposed our grant to CIRM, we did in fact synthesize a universal endosomal escape domain or uEED that is a biomimetic of the very mechanism that SARS-CoV-2 infects cells. We are currently rapidly expanding this research to test in infected cells and preclinical animal models here at UCSD. If/when we successfully solve the RNAi therapeutics delivery problem, this will rapidly open the door to Anti-COVID RNAi therapeutics that will have the capability of targeting all current and future variants of concern.