Orthogonal Fc engineering enables multiplexed delivery of mRNA-encoded bispecific antibodies that constrain viral escape.

Orthogonal Fc engineering enables multiplexed mRNA delivery of bispecific antibodies that neutralize diverse SARS-CoV-2 variants in mice.

• Why it matters: Viral evolution reduces the effectiveness of monoclonal antibody therapies, creating a need for more durable and broad-spectrum treatments against rapidly mutating pathogens like SARS-CoV-2.
• What they did: Researchers designed structure-guided Fc modifications to promote selective homodimerization, allowing co-delivery of multiple mRNA-encoded bispecific antibodies via lipid nanoparticles, and tested their in vivo expression and neutralization capacity in mice.
• The result: The triple bispecific antibody combination achieved high serum neutralizing titers, protected mice from SARS-CoV-2 challenge, and prevented weight loss, demonstrating a promising approach for combating evolving viruses.