Work

Safety and pharmacokinetics of SARS-CoV-2 DNA-encoded monoclonal antibodies in healthy adults: a phase 1 trial

Year: 2025

Type: article

Abstract: Local intramuscular administration of synthetic plasmid DNA (pDNA) encoding monoclonal antibodies (mAb) represents an alternative approach to recombinant protein technology. In this Phase 1, dose escalation study (NCT05293249), we administered a pDNA cocktail encoding AZD5396 and AZD8076, modified versions of the SARS-CoV-2 neutralizing mAb cocktail Evusheld™, by CELLECTRA™ in vivo electroporation technology to healthy adults. Primary endpoints of this study were safety and pharmacokinetics of the in vivo expressed DNA-encoded mAbs (DMAbs). Muscle-expressed DMAbs were detected in the serum of all dosed subjects (N=39), with concentrations reaching 1.39 µg/ml. Remarkably consistent levels of serum DMAbs were measured for at least 72 weeks post-administration in 24/24 subjects who have reached this time point. DMAbs isolated from serum demonstrated SARS-CoV-2 RBD binding and neutralization activity in a standard pseudovirus assay. While the study is ongoing, we have not detected anti-drug antibodies in any of the trial participants thus far. These data represent the first clinical proof-of-concept that synthetic pDNA DMAb technology permits the durable in vivo production of a functional mAb cocktail. This study further underscores the collective importance of synthetic design, formulation, and delivery to achieve biologically relevant expression of gene-encoded biologics. DMAb delivery may represent a valuable strategy against a wide range of diseases which can be targeted with mAbs and their derivatives.

Source: Nature Medicine

DOI: 10.1038/s41591-025-03969-0