Editorial: Single-Domain Antibodies—Biology, Engineering and Emerging Applications

Since the discovery of camelid heavy chain-only antibodies (HCAbs) in 1993 (1) and shark immunoglobulin new antigen receptors (IgNARs) in 1995 (2), and the subsequent recognition that the variable domains of these antibodies (VHHs and VNARs, respectively) function autonomously as single-domain antibodies (sdAbs), sdAbs have found many uses across diverse fields. Early work on naturally-occurring antibodies bearing single variable domains spurred renewed interest in the development of human sdAbs, namely, the light chain variable domains (VLs) and the heavy chain variable domains (VHs) of human conventional antibodies; the first reported sdAbs were actually VHs (3). Synthetic human sdAbs are expected to be less immunogenic than VHHs or VNARs but their development is more challenging, requiring steps to ensure the selection of molecules with good biophysical properties and appropriate affinity. There are several advantages offered by sdAbs over conventional antibodies in a wide variety of diagnostic, research, and therapeutic applications, most notably their ease of production in microbial systems, their potential ability to target cryptic epitopes that are inaccessible to larger molecules, and the fact that they can be readily formatted into more complex molecules. This collection brings together 26 reviews and original research articles that together provide extensive coverage of the developments, opportunities, and challenges associated with this unique class of molecules.