In vivo production of engineered ACE2 decoy protects lungs from SARS-CoV-2 infection.

ABSTRACT: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants repeatedly evade the immune system within short periods. Thus, next-generation therapeutics that are resistant to mutations and can be rapidly supplied to individuals in an emergency are required. Here, we designed an mRNA encoding an engineered angiotensin-converting enzyme 2 (ACE2) decoy, 3N39v4, composed of high-affinity ACE2 and a human immunoglobulin G Fc domain. The 3N39v4-encoded mRNA was encapsulated in lipid nanoparticles for efficient in vivo delivery. Systemic delivery of mRNA in mice resulted in a dose-dependent expression of 3N39v4 in plasma (20-261 μg/mL at 1-10 mg/kg) with sufficient tolerability. An improved pharmacokinetic profile of the produced protein was compared to injection of the 3N39v4 pro

SUBMITTER: Suzuki Y 

PROVIDER: S-EPMC11869860 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature