Abstract

Pros and Cons of Nanobodies for Drug Discovery

Serge Muyldermans, Professor, Vrije Universiteit

Llama and camels have unique antibodies comprising a homodimer of heavy chain polypeptides, whereby the antigen is recognized by virtue of one single domain. A straightforward technology was developed to immunize a camelid, to clone the repertoire of antigen-binding fragments, from which the antigen-specific fragments are identified after phage display selections. The resulting recombinant, antigen-binding single-domain antibody fragments are also referred to as Nanobodies (Nbs) because of their size of 4 nm by 2.5 nm in diameter. Nanobodies are well produced in microbial systems, very robust and highly soluble, bind their cognate antigen with high affinity and specificity. Very often the Nanobody recognizes an epitope that is difficult to target with human or mouse antibodies. The ‘humanization’ of a camel derived single domain antibody is straightforward. Probably, the largest advantage of Nanobodies comes from their strict monomeric behaviour, the ease to tailor them into larger pluripotent constructs and their functionality when expressed intracellularly. Such beneficial properties of Nanobodies over other antigen-binding fragments from conventional antibodies inspired many researchers to employ Nanobodies as a versatile tool in various innovative applications in biotechnology and medicine as: •a research tool to immune-capture the antigen from complex mixtures, •a potent probe to trace (or eliminate) target antigen within living cells, •a diagnostic tool for non-invasive in vivo imaging of tumors, •a therapeutic tool to eradicate tumors or trypanosome infection in mice models, •an anti-venom to protect from scorpion envenoming