Improve Your Research with Custom VHHs (Nanobodies)

VHHs (also known as Nanobodies) are single domain antibody (sdAb) fragments of full-length antibodies (Abs). They have recently attracted considerable interest due to their small size, stability, and robust recognition of biological and chemical targets. VHHs are the smallest functional antigen-binding fragments (Fabs) known and, for purposes of experimental manipulation, can be expressed on E. coli cell surfaces or phage-displayed using recombinant plasmid vectors.

VHHs are derived from the somewhat unusual antibodies found in camelids (i.e., camels, llamas, and alpacas), which, unlike the “canonical” full-length Abs found in humans, mice, and most other mammals, contain only one variable heavy chain and no light chain. Complete camelid antibodies are heavy chain-only antibodies (HCAbs), and VHHs are just the isolated variable domain of HCAbs expressed as a standalone protein. In addition, unlike full-length Ab paratopes, which bind antigens by way of six Complementarity Determining Regions (CDRs), VHHs only have three CDRs in their single heavy chain domain.

VHHs are small, with a molecular size of approximately 12-14 kDa (kiloDaltons). By contrast, a typical IgG antibody has a size of around 150 kDa. Despite their much smaller size and fewer CDRs, VHHs retain complete antigen recognition capacity with high specificity and sensitivity. The small size of VHHs and their functional capability, stability, and minimal disulfide bonds make them ideal for protein engineering applications and expression in mammalian cells, bacterial cells, and bacteriophages. Due to these appealing properties, VHHs are being used in a variety of applications, including biosensing, assay development, and therapeutics.