Single-domain antibody

Single-domain antibody (sdAb), also known as nanobody, is a unique type of antibody that consists of a single monomeric variable antibody domain. Unlike conventional antibodies, which are composed of two heavy chains and two light chains, single-domain antibodies are composed of a single protein domain that can bind to its target antigen.

History

The concept of single-domain antibodies was first introduced in the late 1980s and early 1990s, when researchers discovered that camelids (camels, llamas, and alpacas) and sharks produce functional antibodies devoid of light chains. These unique antibodies, known as heavy-chain antibodies (HCAbs), are composed of two identical heavy chains, each with a single variable domain (VHH) and two constant domains (CH2 and CH3). The VHH domains of these HCAbs are the smallest known naturally occurring, intact antigen-binding fragments, and they are the basis for single-domain antibodies.

Structure and Function

Single-domain antibodies are derived from the VHH domain of camelid HCAbs or the VNAR domain of shark HCAbs. They are small in size (approximately 15 kDa), making them much smaller than conventional antibodies (approximately 150 kDa). Despite their small size, single-domain antibodies are capable of binding to their target antigens with high specificity and affinity.

The small size of single-domain antibodies allows them to bind to epitopes that are inaccessible to conventional antibodies. They are also highly soluble and stable, and they can be easily produced in bacteria and yeast. These properties make single-domain antibodies attractive for various applications in biotechnology and medicine.

Applications

Single-domain antibodies have been used in a wide range of applications, including diagnostics, therapeutics, and research. In diagnostics, they have been used as biomarkers and in immunoassays. In therapeutics, they have been used in the treatment of various diseases, including cancer, infectious diseases, and autoimmune diseases. In research, they have been used as tools for protein purification, crystallography, and microscopy.

Future Perspectives

The field of single-domain antibodies is rapidly evolving, with new applications being developed and existing applications being improved. The unique properties of single-domain antibodies, combined with advances in protein engineering and synthetic biology, are expected to further expand their potential uses in the future.