What are you looking for?

Anna Z. Wec is an Associate Director in Infectious Disease Research at Moderna, where she leads antibody discovery and develops mRNA–LNP strategies for antibody delivery. Previously, she contributed to the development of PEMGARDA at Invivyd, applied machine learning and experimental biology to AAV capsid engineering at Dyno Therapeutics, and discovered antiviral antibodies at Adimab. Her work spans broadly protective antiviral antibodies, T-cell engagers, TCR-based therapeutics, T-cell agonist antibodies, and other next-generation biologic modalities. 

The therapeutic potential of mRNA-encoded antibody combinations is limited by a fundamental problem of molecular assembly—when multiple Fc-containing antibodies are produced in the same cell, non-cognate heavy chains can pair, creating chimeric species with altered specificity, valency, and function. Here, we describe a structure-guided Fc engineering strategy that preserves antibody identity during multiplexed in vivo expression. We redesigned the IgG1 CH3–CH3 interface using steric complementarity and electrostatic steering to favor cognate homodimerization and prevent cross-pairing between independently encoded antibodies. Intact mass spectrometry following in vitro and in vivo mRNA–lipid nanoparticle delivery showed that the optimized interfaces supported assembly of up to four antibodies with minimal detectable mispairing. We then deployed this approach in two distinct therapeutic settings. A three-antibody combination of mRNA-encoded bispecifics targeting non-overlapping SARS-CoV-2 epitopes retained broad serum neutralizing activity against historical, contemporary, and escape variants and protected hACE2-transgenic mice from XBB.1.5 challenge. Separately, co-delivery of PD-1- and LAG-3-targeting VHH–Fc agonists preserved expression, exposure, and activity in a dual inhibitory-receptor agonism strategy for rheumatoid arthritis. Together, these results establish control of Fc assembly as a general design principle for building next-generation mRNA biologics with greater molecular complexity, mechanistic breadth, and therapeutic reach.