HUGO-Nano: The Next Generation of Fully Human VHH Antibodies

Jenny Shan presents engineered mice that produce human-framework single-domain antibodies while retaining camelid-like solubility and stability. Deleting CH1 enables heavy-chain expression without a light chain; selected framework-2 residues support autonomous VHH folding. The talk follows immunization, affinity maturation and binder recovery, comparing this approach with camelid and other transgenic platforms. Validation includes repertoire diversity, immune-cell profiling, target binding and thermal stability. Examples address DLL3, ANG2, CD8 and transferrin-receptor targets, with applications to multispecific antibodies, T-cell engagers, antibody-drug conjugates, CAR-T cells and brain delivery. Platform access and development options are also discussed.