Understanding Nanobodies
Nanobodies are antibody-derived therapeutic proteins that contain the unique structural and functional properties of naturally-occurring heavy-chain antibodies. The Nanobody technology was originally developed following the discovery that camelidae (camels and llamas) possess fully functional antibodies that lack light chains. These heavy-chain antibodies contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Importantly, the cloned and isolated VHH domain is a perfectly stable polypeptide harbouring the full antigen-binding capacity of the original heavy-chain antibody. These newly discovered VHH domains with their unique structural and functional properties form the basis of a new generation of therapeutic antibodies which Ablynx has named Nanobodies.
Ablynx’s Nanobodies combine the advantages of conventional antibodies with important features of small molecule drugs.
Like conventional antibodies, Nanobodies show:
- high target specificity
- high affinity for their target
- low inherent toxicity.
However, like small molecule drugs they have the opportunity to inhibit enzymes and readily access receptor clefts, which is challenging with conventional antibodies.
Furthermore, Nanobodies:
- are generally very stable
- have the potential to be administered by means other than injection
- are easy to manufacture.
To reduce the risk of immunogenicity, Ablynx routinely humanizes its Nanobodies. This is a straightforward procedure because Nanobodies already display relatively high sequence homology to human heavy chain variable domains, typically between 80% and 90% when comparing the framework regions.