Camelids, including llamas and alpacas, are endowed with a unique immune system that encompasses heavy chain only antibodies, in addition to regular 4-chain antibodies. VHHs or nanobodies as they are called, correspond with the antigen binding part of heavy chain antibodies. They are only 15 kDa in size, 10x smaller than a conventional antibody. Camelid nanobodies are a powerful research tool to study protein function in nearly every biological background: in vitro, in cells or in organisms.
Because their cDNAs are available, Camelid nanobodies are amenable to tailored manipulation and modification, in addition to recombinant production and purification. In the meantime, they have found their way to numerous applications. Hence, they are broadly applicable, irrespective of the research domain in which they are used: cancer, inflammation, neurological disorders, amyloid disease, technology development in biochemistry, cell biology, structural biology, immunomodulation, …
Use of nanobodies in biomedical research may improve reproducibility of scientific findings as reported in literature (1,2). Conflicting data have been noticed with several antibodies, and batch to batch variability is an inherent risk. Nanobodies are routinely obtained as cDNA molecules, allowing more straightforward comparison and verification of scientific data.
Recent studies where nanobodies feature as a core technology:
*Deng, W., et al. 2020. Tunable light and drug induced depletion of target proteins. Nat. Commun. doi:10.1038/s41467-019-14160-8.
*Galazzo, L., et al. 2020. Spin-labeled nanobodies as protein conformational reporters for electron paramagnetic resonance in cellular membranes. Proc. Natl. Acad. Sci. U. S. A. doi:10.1073/pnas.1913737117.
*Farrants, H., et al. 2020. Chemogenetic Control of Nanobodies. Nat. Methods. doi:10.1038/s41592-020-0746-7.
*Che, T., et al. 2018. Structure of the Nanobody-Stabilized Active State of the Kappa Opioid Receptor. Cell. doi:10.1016/j.cell.2017.12.011.
*Yen, H.Y., et al. 2018. PtdIns(4,5)P2 stabilizes active states of GPCRs and enhances selectivity of G-protein coupling. Nature. doi:10.1038/s41586-018-0325-6.
*Chamma, I., et al. 2017. Optimized labeling of membrane proteins for applications to super-resolution imaging in confined cellular environments using monomeric streptavidin. Nat. Protoc. doi:10.1038/nprot.2017.010.