Camelid single domain antibody (VHH) technology

VHHs molecules are single domain antibodies derived from heavy chain-only antibodies found in camelid species. They are alsocommonly known as NANOBODY® molecules, a registered trademark of Ablynx N.V. These small 15 kDa proteins bind to target molecules with affinity and specificity. Bacterially expressed VHHs can be fluorescently labeled to visualize the target in advanced microscopy techniques, or modified with biochemical handles for protein purification. Unlike antibodies, VHHs can also be expressed in the cytosol of living cells to visualize and perturb function of endogenous targets in living cells.

To generate VHH constructs, we immunize alpacas and llamas and subsequently construct a plasmid library encoding the diversity of VHH molecules generated in the animal. We then apply phage display as well as functional screens to identify suitable VHHs. We are in the process of assembling a comprehensive collection of VHHs targeting the major innate immune signaling pathways. These allow us to specifically interfere with (or activate) the distinct steps of innate immune signaling to learn mechanistic lessons.

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